@article{fogle_tompkins_campbell_sumner_tompkins_2011, title={Fozivudine Tidoxil as Single-Agent Therapy Decreases Plasma and Cell-Associated Viremia during Acute Feline Immunodeficiency Virus Infection}, volume={25}, ISSN={["1939-1676"]}, DOI={10.1111/j.1939-1676.2011.0699.x}, abstractNote={Background:  Feline immunodeficiency virus (FIV) is a lentivirus that infects domestic and wild felidae and the course of disease is similar to that of human immunodeficiency virus infection. The thymidine nucleoside analog fozivudine (FZD) tidoxil is a lipid—zidovudine (ZDV) conjugate and member of the family of nucleoside reverse transcriptase (RT) inhibitors (NRTIs).}, number={3}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Fogle, J. E. and Tompkins, W. A. and Campbell, B. and Sumner, D. and Tompkins, M. B.}, year={2011}, pages={413–418} }
 @article{fogle_mexas_tompkins_tompkins_2010, title={CD4(+)CD25(+) T Regulatory Cells Inhibit CD8(+) IFN-gamma Production During Acute and Chronic FIV Infection Utilizing a Membrane TGF-beta-Dependent Mechanism}, volume={26}, ISSN={["1931-8405"]}, DOI={10.1089/aid.2009.0162}, abstractNote={CD8(+) lymphocytes are critical to the control and elimination of viral pathogens. Impaired CD8(+) responses are well recognized in lentiviral infections; however, the mechanisms underlying CD8(+) impairment remain elusive. Using the feline immunodeficiency virus (FIV) model for human AIDS, we reported previously that CD4(+)CD25(+) Treg cells in both the acute and long-term, asymptomatic phase of infection are constitutively activated and suppress CD4(+)CD25(-) T cell responses. In the current study, we have demonstrated that CD4(+)CD25(+) Treg cells suppress CD8(+) responses to immune stimulation during both the acute and chronic, asymptomatic phase of FIV infection and that the mechanism of suppression may be mediated by membrane-associated TGF-beta (mTGF-beta) on CD4(+)CD25(+) lymphocytes. Depletion of CD4(+)CD25(+) lymphocytes from lymph node suspensions significantly enhanced production of IFN-gamma during the acute phase of infection and coculture of CD8(+) lymphocytes with CD4(+)CD25(+) lymphocytes resulted in suppression of CD8(+) IFN-gamma during both the acute and chronic stages of infection. FACS analysis indicated that there was TGF-betaRII upregulation on CD8(+) cells from FIV(+) cats during the acute and chronic stage of infection. In addition, there was upregulation of mTGF-beta on the CD4(+)CD25(+) subset in chronically infected cats. In support of activation of the TGF-beta signaling pathway, Western blotting showed Smad 2 phosphorylation in CD8(+) targets following CD4(+)CD25(+)/CD8(+) coculture. These results demonstrate the suppressive effect CD4(+)CD25(+) Treg cells have on the CD8(+) immune response during the acute and chronic stages of FIV infection and suggest that the mechanism of suppression may be mediated by mTGF-beta.}, number={2}, journal={AIDS RESEARCH AND HUMAN RETROVIRUSES}, author={Fogle, Jonathan E. and Mexas, Angela M. and Tompkins, Wayne A. and Tompkins, Mary B.}, year={2010}, month={Feb}, pages={201–216} }
 @article{fogle_tompkins_tompkins_2010, title={CD4(+)CD25(+) T regulatory cells from FIV+ cats induce a unique anergic profile in CD8(+) lymphocyte targets}, volume={7}, ISSN={["1742-4690"]}, DOI={10.1186/1742-4690-7-97}, abstractNote={Abstract}, journal={RETROVIROLOGY}, author={Fogle, Jonathan E. and Tompkins, Wayne A. and Tompkins, Mary B.}, year={2010}, month={Nov} }
 @article{mexas_fogle_tompkins_tompkins_2008, title={CD4(+)CD25(+) regulatory T cells are infected and activated during acute FIV infection}, volume={126}, ISSN={["1873-2534"]}, DOI={10.1016/j.vetimm.2008.08.003}, abstractNote={HIV-induced AIDS may be mediated by the activation of immunosuppressive CD4+CD25+ T regulatory cells (Treg cells). Treg cells have been shown to regulate CD4+ and CD8+ immune responses to HIV and FIV antigens in vitro. We tested the hypothesis that Treg cells become infected and activated during the acute infection with FIV leading to the suppression of CD4+ T helper cell responses. Cats were experimentally infected with FIV-NCSU1 and blood and lymph node cells were collected at weekly intervals following inoculation. Real-time RT-PCR was used to determine plasma viremia and the relative expression of FIV, FoxP3, TGF-β, and GAPDH mRNA copies in CD4+CD25+ and CD4+CD25− T cell subsets. Flow cytometry was used to assess the absolute numbers of each cell type and the expression of surface TGF-β and intracellular FoxP3 in CD4+CD25+ and CD4+CD25− T cells at each time-point. Treg suppression of IL-2 production in CD4+ T helper cells was assessed by ELISPOT assays. Our results showed that peak viremia occurred at 2 weeks post infection and correlated with maximal infectivity in CD4+CD25+ T cell populations. FIV-gag-mRNA levels were higher in CD4+CD25+ T cells than CD4+CD25− T cells throughout the acute phase of infection. Induction of FoxP3 and TGF-β indicated activation of Treg cells during the acute stage infection, which was confirmed by Treg cell suppression of IL-2 production by CD4+ Th cells in an ELISPOT assay. Our findings support the hypothesis that early activation of Treg immunosuppressor function may limit an effective anti-FIV response, contributing to the establishment of chronic infection and the immunodeficiency caused by this virus.}, number={3-4}, journal={VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY}, author={Mexas, Angela M. and Fogle, Jonathan E. and Tompkins, Wayne A. and Tompkins, Mary B.}, year={2008}, month={Dec}, pages={263–272} }
 @article{lankford_petty_la voy_reckling_tompkins_dean_2008, title={Cloning of feline FOXP3 and detection of expression in CD4+CD25+ regulatory T cells}, volume={122}, ISSN={["1873-2534"]}, DOI={10.1016/j.vetimm.2007.11.007}, abstractNote={Regulatory T cells (Treg) are increased and directly infected by feline immunodeficiency virus (FIV) and likely play a role in other feline autoimmune, neoplastic, and infectious diseases. Phenotypically, Treg are best characterized by surface expression of CD4 and CD25 and intranuclear expression of the forkhead transcription factor Foxp3. Our objective was to clone and sequence feline FOXP3 for the purpose of developing assays to enhance studies of feline Treg. We determined the feline FOXP3 is 1293 nucleotides in length and codes for a protein that shares high homology to other species. A splice variant devoid of exon 2 was also identified. A real-time PCR assay was developed and used to show Foxp3 mRNA expression occurs primarily in CD4+CD25+ T cells. Two cross-reacting antibodies were identified by immunocytochemical staining of HEK293 cells transfected with feline FOXP3. The antibody labeling confirmed the nuclear localization of the protein. A flow cytometric assay was also validated and used to correlate the phenotypic and functional characteristics of feline Treg induced by treatment of lymph node lymphocytes with flagellin or LPS in combination with mitogen or IL2. Together, these studies provide useful tools to further investigate Foxp3 and Tregs in cats.}, number={1-2}, journal={VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY}, author={Lankford, Susan and Petty, Christopher and La Voy, Alora and Reckling, Stacie and Tompkins, Wayne and Dean, Gregg A.}, year={2008}, month={Mar}, pages={159–166} }
 @article{tompkins_tompkins_2008, title={Lentivirus-induced immune dysregulation}, volume={123}, ISSN={["0165-2427"]}, DOI={10.1016/j.vetimm.2008.01.011}, abstractNote={FIV/HIV infections are associated with an early robust humoral and cellular anti-viral immune response followed by a progressive immune suppression that eventually results in AIDS. Several mechanisms responsible for this immune dysfunction have been proposed including cytokine dysregulation, immunologic anergy and apoptosis, and inappropriate activation of immune regulatory cells. Studies on FIV infection provide evidence for all three. Cytokine alterations include decreases in IL2 and IL12 production and increases in IFNgamma and IL10 in FIV(+) cats compared to normal cats. The elevated IL10:IL12 ratio is associated with the inability of FIV(+) cats to mount a successful immune response to secondary pathogens. Additionally, chronic antigenic (FIV) stimulation results in an increase in the percent of activated T cells expressing B7 and CTLA4 co-stimulatory molecules in infected cats. The expression of these molecules is associated with T cells that are undergoing apoptosis in the lymph nodes. As ligation of CTLA4 by B7 transduces a signal for induction of anergy, one can speculate that the activated T cells are capable of T cell-T cell interactions resulting in anergy and apoptosis. The inability of CD4(+) cells from FIV(+) cats to produce IL2 in response to recall antigens and the gradual loss of CD4(+) cell numbers could be due to B7-CTLA4 interactions. The chronic antigenemia may also lead to activation of CD4(+)CD25(+) T regulatory cells. Treg cells from FIV(+) cats are chronically activated and inhibit the mitogen-induced proliferative response of CD4(+)CD25(-) by down-regulating IL2 production. Although Treg cell activation can be antigen-specific, the suppressor function is not, and thus activated Treg cells would suppress responses to secondary pathogens as well as to FIV. Concomitant with the well-known virus-induced immune suppression is a progressive immune hyper-activation. Evidence for immune hyper-activation includes polyclonal B cell responses, gradual replacement of naïve CD4(+) and CD8(+) T cell phenotypes with activation phenotypes (CD62L(-), B7(+), CTLA4(+)), and the chronic activation of CD4(+)CD25(+) Treg cells. Thus lentivirus infections lead to severe immune dysregulation manifested as both chronic immune suppression and chronic immune activation. FIV infection of cats provides a number of advantages over other lentivirus infections as a model to study this immune dysregulation. It is a natural infection that has existed in balance with the cat's immune system for thousands of years. As such, the natural history and pathogenesis provides an excellent model to study the long-term relationships between AIDS lentivirus and host immune system function/dysregulation.}, number={1-2}, journal={VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY}, author={Tompkins, Mary B. and Tompkins, Wayne A.}, year={2008}, month={May}, pages={45–55} }
 @article{petty_tompkins_tompkins_2008, title={Transforming growth factor-beta/transforming growth factor-beta RII signaling may regulate CD4(+)CD25(+) T-regulatory cell homeostasis and suppressor function in feline AIDS lentivirus infection}, volume={47}, ISSN={["1525-4135"]}, DOI={10.1097/QAI.0b013e318160df70}, abstractNote={We have reported that CD4+CD25+ T-regulatory (Treg) cells are fully activated for suppressor function in feline immunodeficiency virus (FIV)-infected cats. Studies have suggested that surface transforming growth factor-β (TGFβ; membrane TGFβ [mTGFβ]) is a feature of activated CD4+CD25+ Treg cells and may play a role in Treg homeostasis and suppressor function. Herein, we explore the role of TGFβ in feline Treg homeostasis and suppressor function and what effect FIV infection of cats might have on these processes. Stimulation of CD4+CD25− T helper (Th) cells with Concanavalin A (ConA) plus TGFβ converts them to Treg-like cells capable of suppressor function. Reverse-transcription polymerase chain reaction and flow cytometry revealed that these ConA/TGFβ-converted Treg cells upregulate Foxp3 and mTGFβ. ConA stimulation of CD4+CD25− T cells upregulates TGFβ receptor II (RII), and pretreatment of these cells with anti-TGFβ-RII antibodies blocks the TGFβ-induced conversion to Treg cells. Pretreatment of ConA/TGFβ-converted Treg cells with anti-TGFβ antibodies also abrogates their suppressor function, suggesting that Treg homeostasis and suppressor function may be mediated by mTGFβ. Finally, we show that treatment of CD4+CD25+ mTGFβ-positive Treg cells from FIV-infected cats with anti-TGFβ antibodies or treatment of ConA-stimulated CD4+CD25− Th target cells with anti-TGFβ-RII antibodies diminishes suppressor function. These data suggest that the recruitment of Treg cells from the Th pool and suppressor function of Treg cells are dependent on the TGFβ/TGFβ-RII signaling pathway and that this pathway is constitutively upregulated in asymptomatic chronically FIV-infected cats.}, number={2}, journal={JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES}, author={Petty, Christopher S. and Tompkins, Mary B. and Tompkins, Wayne A.}, year={2008}, month={Feb}, pages={148–160} }
 @article{joshi_garg_tompkins_tompkins_2005, title={Different thresholds of T cell activation regulate FIV infection of CD4(+)CD25(+) and CD4(+)CD25(-) cells}, volume={335}, ISSN={["0042-6822"]}, DOI={10.1016/j.virol.2005.02.016}, abstractNote={Cellular activation plays an important role in retroviral replication. Previously, we have shown that CD4+CD25+ T cells by the virtue of their partially activated phenotype represent ideal candidates for a productive feline immunodeficiency virus (FIV) infection. In the present study, we extended our previous observations with regard to FIV replication in CD4+CD25+ and CD4+CD25− cells under different stimulation conditions. Both CD4+CD25+ and CD4+CD25− cells remain latently infected in the absence of IL-2 or concanvalinA (ConA), respectively; harboring a replication competent provirus capable of reactivation several days post-infection. While CD4+CD25+ cells require low levels of exogenous IL-2 and virus inputs for an efficient FIV replication, CD4+CD25− T cells can only be productively infected in the presence of either high concentrations of IL-2 or high virus titers, even in the absence of mitogenic stimulation. Interestingly, while high virus input activates CD4+CD25− cells to replicate FIV, it induces apoptosis in a high percentage of CD4+CD25+ T cells. High IL-2 concentrations but not high virus inputs lead to surface upregulation of CD25 and significant cellular proliferation in CD4+CD25− cells. These results suggest that CD4+CD25+ and CD4+CD25− T cells have different activation requirements which can be modulated by both viral and cytokine stimuli to reach threshold activation levels in order to harbor a productive FIV infection. This holds implications in vivo for CD4+CD25+ and CD4+CD25− cells to serve as potential reservoirs of a productive and latent FIV infection.}, number={2}, journal={VIROLOGY}, author={Joshi, A and Garg, H and Tompkins, MB and Tompkins, WA}, year={2005}, month={May}, pages={212–221} }
 @article{joshi_garg_tompkins_tompkins_2005, title={Preferential feline immunodeficiency virus (FIV) infection of CD4(+) CD25(+) T-regulatory cells correlates both with surface expression of CXCR4 and activation of FIV long terminal repeat binding cellular transcriptional factors}, volume={79}, ISSN={["0022-538X"]}, DOI={10.1128/JVI.79.8.4965-4976.2005}, abstractNote={ABSTRACT}, number={8}, journal={JOURNAL OF VIROLOGY}, author={Joshi, A and Garg, H and Tompkins, MB and Tompkins, WA}, year={2005}, month={Apr}, pages={4965–4976} }
 @article{vahlenkamp_tompkins_tompkins_2005, title={The role of CD4(+)CD25(+) regulatory T cells in viral infections}, volume={108}, ISSN={["1873-2534"]}, DOI={10.1016/j.vetimm.2005.07.011}, abstractNote={Many virus infections result in the suppression of one or more functions of the immune system. Multiple mechanisms have been proposed to explain viral-induced immunosuppression, including an imbalance in the cellular Th1/Th2 or cytokine profile, induction of anergy, depletion of effector cells and most recently the activation of CD4+CD25+ regulatory T (T reg) cells. CD4+CD25+ T reg cells are a subset of circulating CD4+ T cells with suppressive properties. CD4+CD25+ T reg cells were first identified in mice as cells capable of maintaining self-tolerance by suppressing autoreactive T cells. This review focuses on interactions between CD4+CD25+ T reg cells and viral pathogens. Most cases in which CD4+CD25+ T reg cells participate in response to infection reported so far involve chronic or persistent viral infections. Examples have been growing recently and include members of different viral families including retroviridae, herpesviridae and picornaviridae. It is currently not known how microbes are recognized by CD4+CD25+ T reg cells and whether exoantigen-specific T reg cells are of the same lineage as self-reacting natural T reg cells or represent peripherally induced counterparts derived from CD4+CD25− T cells. The findings that T reg cells influence the functional immunity during viral infections, however, might indicate that, in some cases, virus-specific T reg cells not only influence immune pathology or prevent pathogen elimination but also can promote a generalized state of immunosuppression in vivo such that the host is more susceptible to secondary infections with other pathogens or has reduced resistance to tumors. Conceivably, the activities of T reg cells might be one of the contributing reasons why it has been difficult so far to produce effective vaccines against some persisting viral infections.}, number={1-2}, journal={VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY}, author={Vahlenkamp, TW and Tompkins, MB and Tompkins, WAF}, year={2005}, month={Oct}, pages={219–225} }
 @article{vahlenkamp_bull_dow_collisson_winslow_phadke_tompkins_tompkins_2004, title={B7(+)CTLA4(+) T cells engage in T-T cell interactions that mediate apoptosis: a model for lentivirus-induced T cell depletion}, volume={98}, ISSN={["0165-2427"]}, DOI={10.1016/j.vetimm.2003.12.006}, abstractNote={Apoptosis in lymph node (LN) T cells of feline immunodeficiency virus (FIV)-infected cats is associated with cells co-expressing B7.1 and B7.2 costimulatory molecules, and their ligand CTLA4. To study the possibility of B7.1/B7.2-CTLA4 mediated T-T interactions and the predicted induction of T cell apoptosis in vitro, costimulatory molecules were up-regulated on CD4+ and CD8+ T cells by mitogen stimulation. B7.1 expression on in vitro stimulated CD4+ and CD8+ cells increased within 24h; B7.2 and CTLA4 expression increased after 48-72 h. Apoptosis, as analyzed by terminal deoxynucleotidyl transferase (transferase nick end labeling, TUNEL)-based staining followed by three color flow cytometric analysis, correlated to the cells expressing B7 and/or CTLA4. Blocking experiments revealed that CD4+ and CD8+ T cell apoptosis could be significantly inhibited with anti-B7 antibodies. As FIV infection results in immune activation with a T cell phenotype similar to that of the in vitro activated T cells, the data support the hypothesis that the chronic expansion of B7+CTLA4+ LN T cells in infected cats allows for T-T cell interactions resulting in T cell depletion and eventually the development of AIDS.}, number={3-4}, journal={VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY}, author={Vahlenkamp, TW and Bull, ME and Dow, JL and Collisson, EW and Winslow, BJ and Phadke, AP and Tompkins, WAF and Tompkins, MB}, year={2004}, month={Apr}, pages={203–214} }
 @article{levy_liang_ritchey_davidson_tompkins_tompkins_2004, title={Failure of FIV-infected cats to control Toxoplasma gondii correlates with reduced IL2, IL6, and IL12 and elevated IL10 expression by lymph node T cells}, volume={98}, ISSN={["0165-2427"]}, DOI={10.1016/j.vetimm.2003.11.002}, abstractNote={Increased susceptibility to intracellular pathogens in HIV-infected individuals and FIV-infected cats is attributed to a defective T-helper 1 (Th1) immune response. However, little is known about specific cytokine responses to secondary pathogens. To address this question, control and FIV-infected cats were challenged with Toxoplasma gondii, and lymph node cells analyzed for cytokine mRNA expression. Twenty-four weeks post-FIV infection, prior to T. gondii challenge, IL2 and IL12 mRNAs were depressed, whereas IL10 and IFNγ mRNAs were increased in CD4+ and CD8+ subsets. Following T. gondii challenge, control cats showed increased expression of IL2, IFNγ, IL10, IL12, and IL6 mRNAs. In contrast, IL2, IL6, IFNγ, and IL12 mRNAs were suppressed in FIV–T. gondii co-infected cats, whereas IL10 remained at the high prechallenge levels. IFNγ and IL10 mRNAs were produced by both CD4+ and CD8+ cells in FIV–T. gondii cats. Elevated IL10 may suppress a Th1 cytokine response to T. gondii challenge.}, number={1-2}, journal={VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY}, author={Levy, JK and Liang, YH and Ritchey, JW and Davidson, MG and Tompkins, WA and Tompkins, MB}, year={2004}, month={Mar}, pages={101–111} }
 @article{garg_joshi_tompkins_2004, title={Feline immunodeficiency virus envelope glycoprotein mediates apoptosis in activated PBMC by a mechanism dependent on gp41 function}, volume={330}, ISSN={["0042-6822"]}, DOI={10.1016/j.virol.2004.10.007}, abstractNote={Feline Immunodeficiency Virus (FIV) is a lentivirus that causes immunodeficiency in cats, which parallels HIV-1-induced immunodeficiency in humans. It has been established that HIV envelope (Env) glycoprotein mediates T cell loss via a mechanism that requires CXCR4 binding. The Env glycoprotein of FIV, similar to HIV, requires CXCR4 binding for viral entry, as well as inducing membrane fusion leading to syncytia formation. However, the role of FIV Env in T cell loss and the molecular mechanisms governing this process have not been elucidated. We studied the role of Env glycoprotein in FIV-mediated T cell apoptosis in an in vitro model. Our studies demonstrate that membrane-expressed FIV Env induces apoptosis in activated feline peripheral blood mononuclear cells (PBMC) by a mechanism that requires CXCR4 binding, as the process was inhibited by CXCR4 antagonist AMD3100 in a dose-dependent manner. Interestingly, studies regarding the role of CD134, the recently identified primary receptor of FIV, suggest that binding to CD134 may not be important for induction of apoptosis in PBMC. However, inhibiting Env-mediated fusion post CXCR4 binding by FIV gp41-specific fusion inhibitor also inhibited apoptosis. Under similar conditions, a fusion-defective gp41 mutant was unable to induce apoptosis in activated PBMC. Our findings are the first report suggesting the potential of FIV Env to mediate apoptosis in bystander cells by a process that is dependent on gp41 function.}, number={2}, journal={VIROLOGY}, author={Garg, H and Joshi, A and Tompkins, WA}, year={2004}, month={Dec}, pages={424–436} }
 @article{vahlenkamp_tompkins_tompkins_2004, title={Feline immunodeficiency virus infection phenotypically and functionally activates immunosuppressive CD4(+)CD25(+) T regulatory cells}, volume={172}, ISSN={["1550-6606"]}, DOI={10.4049/jimmunol.172.8.4752}, abstractNote={Abstract}, number={8}, journal={JOURNAL OF IMMUNOLOGY}, author={Vahlenkamp, TW and Tompkins, MB and Tompkins, WAF}, year={2004}, month={Apr}, pages={4752–4761} }
 @article{garg_fuller_tompkins_2004, title={Mechanism of feline immunodeficiency virus envelope glycoprotein-mediated fusion}, volume={321}, ISSN={["0042-6822"]}, DOI={10.1016/j.virol.2004.01.006}, abstractNote={Feline immunodeficiency virus (FIV) shares remarkable homology to primate lentiviruses, human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV). The process of lentiviral env glycoprotein-mediated fusion of membranes is essential for viral entry and syncytia formation. A detailed understanding of this phenomenon has helped identify new targets for antiviral drug development. Using a model based on syncytia formation between FIV env-expressing cells and a feline CD4+ T cell line we have studied the mechanism of FIV env-mediated fusion. Using this model we show that FIV env-mediated fusion mechanism and kinetics are similar to HIV env. Syncytia formation could be blocked by CXCR4 antagonist AMD3100, establishing the importance of this receptor in FIV gp120 binding. Interestingly, CXCR4 alone was not sufficient to allow fusion by a primary isolate of FIV, as env glycoprotein from FIV-NCSU1 failed to induce syncytia in several feline cell lines expressing CXCR4. Syncytia formation could be inhibited at a post-CXCR4 binding step by synthetic peptide T1971, which inhibits interaction of heptad repeat regions of gp41 and formation of the hairpin structure. Finally, using site-directed mutagenesis, we also show that a conserved tryptophan-rich region in the membrane proximal ectodomain of gp41 is critical for fusion, possibly at steps post hairpin structure formation.}, number={2}, journal={VIROLOGY}, author={Garg, H and Fuller, FJ and Tompkins, WAF}, year={2004}, month={Apr}, pages={274–286} }
 @article{joshi_vahlenkamp_garg_tompkins_tompkins_2004, title={Preferential replication of FIV in activated CD4(+)CD25(+)T cells independent of cellular proliferation}, volume={321}, ISSN={["0042-6822"]}, DOI={10.1016/j.virol.2004.01.014}, abstractNote={Studies attempting to identify reservoirs of HIV-1 latency have documented that the virus persists as both a latent and productive infection in subsets of CD4+ cells. Reports regarding establishment of a stable HIV-1 infection in quiescent T cells in vitro, however, are controversial. In the present study, we investigated the susceptibility of naive and activated CD4+ cell subsets (distinguished by differential expression of CD25) to feline immunodeficiency virus (FIV) infection, their ability to replicate the virus, and potentially act as a reservoir for virus persistence in infected animals. While both CD4+CD25+ and CD4+CD25− cells are susceptible to FIV infection in vitro and in vivo, only CD4+CD25+ cells produce infectious virions when cultured with interleukin-2 (IL-2). Latently infected CD4+CD25− cells produce infectious virions following ConcanvalinA (ConA) stimulation, which correlates with upregulated surface expression of CD25. In contrast to CD4+CD25− cells, CD4+CD25+ cells remain unresponsive to mitogen stimulation and are relatively resistant to apoptosis whether or not infected with FIV. The ability of CD4+CD25+ cells to replicate FIV efficiently in the presence of IL-2 but remain anergic and unresponsive to apoptotic signaling suggests that these cells may provide a reservoir of productive FIV infection. On the contrary, CD4+CD25− cells seem to establish as latent viral reservoirs capable of being reactivated after stimulation.}, number={2}, journal={VIROLOGY}, author={Joshi, A and Vahlenkamp, TW and Garg, H and Tompkins, WAF and Tompkins, MB}, year={2004}, month={Apr}, pages={307–322} }
 @article{bull_vahlenkamp_dow_collisson_winslow_phadke_tompkins_tompkins_2004, title={Spontaneous T cell apoptosis in feline immunodeficiency virus (FIV)-infected cats is inhibited by IL2 and anti-B7.1 antibodies}, volume={99}, ISSN={["1873-2534"]}, DOI={10.1016/j.vetimm.2004.01.010}, abstractNote={Lymph node (LN) T cells from feline immunodeficiency virus (FIV)-infected cats have an increased expression of B7 co-stimulatory molecules as well as their ligand CTLA4, resembling an activation phenotype shown to induce anergy and apoptosis in activated T cells. In addition, LN T cells from FIV-infected cats also show increased spontaneous apoptosis compared to uninfected animals. The apoptosis observed in these animals occurs primarily in T cells expressing B7 and CTLA4, suggesting a role for B7 and CTLA4 interactions in the induction of anergy/apoptosis. In order to investigate the role of B7 and CTLA4 interactions on T cell apoptosis in LN T cells from FIV-infected cats, we performed blocking experiments by measuring T cell apoptosis in LN T cell cultures treated with anti-feline B7.1, B7.2, and CTLA4 specific antibodies, as well as interleukin (IL)-2. The addition of IL2, the primary cytokine produced by B7/CD28 interactions, resulted in a significant decrease of T cell apoptosis in cultured LN cells as assessed by two-color flow cytometry and TUNEL assay. The addition of anti-B7.1 antibodies significantly inhibited T cell apoptosis in FIV-infected cats with low-level plasma viremia, while addition of anti-B7.2 and anti-CTLA4 antibodies had no affect. These results suggest a role of B7 signaling in the increased spontaneous apoptosis observed in LN T cells from FIV-infected animals.}, number={1-2}, journal={VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY}, author={Bull, ME and Vahlenkamp, TW and Dow, JL and Collisson, EW and Winslow, BJ and Phadke, AP and Tompkins, MB and Tompkins, WAF}, year={2004}, month={May}, pages={25–37} }
 @article{bull_kennedy-stoskopf_levine_loomis_gebhard_tompkins_2003, title={Evaluation of T lymphocytes in captive African lions (Panthera leo) infected with feline immunodeficiency virus}, volume={64}, ISSN={["0002-9645"]}, DOI={10.2460/ajvr.2003.64.1293}, abstractNote={Abstract}, number={10}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Bull, ME and Kennedy-Stoskopf, S and Levine, JF and Loomis, M and Gebhard, DG and Tompkins, WAF}, year={2003}, month={Oct}, pages={1293–1300} }
 @article{medinas_lambert_tompkins_2002, title={C-terminal gp40 peptide analogs inhibit feline immunodeficiency virus: Cell fusion and virus spread}, volume={76}, ISSN={["0022-538X"]}, DOI={10.1128/JVI.76.18.9079-9086.2002}, abstractNote={ABSTRACT}, number={18}, journal={JOURNAL OF VIROLOGY}, author={Medinas, RJ and Lambert, DM and Tompkins, WA}, year={2002}, month={Sep}, pages={9079–9086} }
 @article{burkhard_valenski_leavell_dean_tompkins_2002, title={Evaluation of FIV protein-expressing VEE-replicon vaccine vectors in cats}, volume={21}, ISSN={["0264-410X"]}, DOI={10.1016/S0264-410X(02)00455-3}, abstractNote={Venezuelan equine encephalitis (VEE) virus-replicon particles (VRP) were used to generate feline immunodeficiency virus (FIV) Gag- and ENV-expressing vaccine vectors. Serum and mucosal FIV-specific antibody was detected in cats immunized subcutaneously, once monthly for 5 months, with FIV-expressing VRP. Expansion of the CD8+ L-selectin negative phenotype and transient CD8+ noncytolytic suppressor activity were seen in cats immunized with FIV-expressing or control VRP. Despite induction of FIV-specific immune responses and nonspecific suppressor responses, all cats became infected following vaginal challenge with high dose, pathogenic cell-associated FIV-NCSU(1) although relative early maintenance of CD4+ cells was seen in FIV-immunized cats.}, number={3-4}, journal={VACCINE}, author={Burkhard, MJ and Valenski, L and Leavell, S and Dean, GA and Tompkins, WAF}, year={2002}, month={Dec}, pages={258–268} }
 @article{tompkins_bull_dow_ball_collisson_winslow_phadke_vahlenkamp_tompkins_2002, title={Feline immunodeficiency virus infection is characterized by B7(+)CTLA4(+) T cell apoptosis}, volume={185}, ISSN={["0022-1899"]}, DOI={10.1086/339847}, abstractNote={The B7.1 and B7.2 costimulatory molecules on antigen-presenting cells provide second signals for regulating T cell immune responses via CD28 and cytotoxic T lymphocyte antigen 4 (CTLA4) on T cells. CD28 signals cell proliferation, whereas CTLA4 signals for anergy or apoptosis, terminating the immune response. Because T cell apoptosis and immunodeficiency is a characteristic of feline immunodeficiency virus (FIV)-infected cats, it is possible that negative T cell signaling via B7 and CTLA4 may be favored in these cats. Flow cytometry revealed high percentages of CD8+ and CD4+ cells expressing B7.1, B7.2, and CTLA4 in lymph nodes of FIV-positive cats and a large fraction of CTLA4+ T cells coexpressing B7.1 and B7.2. Three-color analysis with anti-B7.1, anti-B7.2, or anti-CTLA4 and TUNEL (terminal deoxynucleotidyl transferase nick-end-labeling) analysis revealed that apoptosis was a characteristic of B7.1+ B7.2+ CTLA4+ T cells. These data support the hypothesis that lymph node apoptosis and immune deterioration in FIV-infected cats results from chronic B7.1- and/or B7.2-CTLA4-mediated T-T interactions.}, number={8}, journal={JOURNAL OF INFECTIOUS DISEASES}, author={Tompkins, MB and Bull, ME and Dow, JL and Ball, JM and Collisson, EW and Winslow, BJ and Phadke, AP and Vahlenkamp, TW and Tompkins, WA}, year={2002}, month={Apr}, pages={1077–1093} }
 @article{bragg_childers_tompkins_tompkins_meeker_2002, title={Infection of the choroid plexus by feline immunodeficiency virus}, volume={8}, ISSN={["1355-0284"]}, DOI={10.1080/13550280290049688}, abstractNote={The human, simian, and feline immunodeficiency viruses rapidly penetrate into the brain and trigger an inflammatory process that can lead to significant neurologic disease. However, the mechanisms that permit efficient trafficking of macrophage-tropic and the more neurotoxic lymphocytotropic isolates are still poorly understood. One potential source of virus entry may be the blood-CSF barrier provided by the choroid plexus. Infected cells are often detected within the choroid plexus but it is unclear whether this reflects trafficking cells or infection of the large macrophage population within the choroidal stroma. To address this issue, we cultured fetal feline choroid plexus and evaluated the ability of feline immunodeficiency virus (FIV) to establish a primary infection. Significant provirus was detected in macrophage-enriche d choroid plexus cultures as well as in the choroid plexus of cats infected in vivo. FIV p24 antigen production in vitro was very low but detectable. Addition of a feline T-cell line to macrophages inoculated with FIV resulted in a dense clustering of the T cells over macrophages with dendritic cell-like morphologies and a robust productive infection. The direct infection of choroid plexus macrophages with FIV, the efficient transfer of the infection to T cells indicate that the choroid plexus can be a highly efficient site of viral infection and perhaps trafficking of both macrophage-tropic and T-cell-tropic viruses into the CNS.}, number={3}, journal={JOURNAL OF NEUROVIROLOGY}, author={Bragg, DC and Childers, TA and Tompkins, MB and Tompkins, WA and Meeker, RB}, year={2002}, month={Jun}, pages={211–224} }
 @article{ma_kennedy-stoskopf_jaynes_thurmond_tompkins_2002, title={Inhibitory activity of synthetic peptide antibiotics on feline immunodeficiency virus infectivity in vitro}, volume={76}, ISSN={["1098-5514"]}, DOI={10.1128/JVI.76.19.9952-9961.2002}, abstractNote={ABSTRACT}, number={19}, journal={JOURNAL OF VIROLOGY}, author={Ma, J and Kennedy-Stoskopf, S and Jaynes, JM and Thurmond, LM and Tompkins, WA}, year={2002}, month={Oct}, pages={9952–9961} }
 @article{bull_gebhard_tompkins_kennedy-stoskopf_2002, title={Polymorphic expression in the CD8 alpha chain surface receptor of African lions (Panthera leo)}, volume={84}, ISSN={["1873-2534"]}, DOI={10.1016/S0165-2427(01)00401-9}, abstractNote={Free-ranging African lion (Panthera leo) peripheral blood mononuclear cells (PBMC) were examined using flow cytometry and antibodies developed for use in the domestic cat to determine if phenotypic changes occurred in lion lymphocytes as a result of feline immunodeficiency virus (FIV) infection. The percentage of CD8 cells from lion peripheral blood was considerably lower than in the domestic cat. Lions with elevated levels of CD8+ cells were typically infected with FIV, similar to observations in the domestic cat. Antibodies against the alpha chain of the CD8 receptor (monoclonal antibody (mAb) 3.357) did not react consistently in all lions examined. Flow cytometric analysis determined that approximately 82 and 80% of the animals from Kruger and Hluhluwe-Umfolozi National Parks in South Africa reacted with the monoclonal antibody against the alpha chain of CD8 receptor, while only 17% of the lions in Etosha National Park in Namibia cross-reacted with the CD8alpha chain. There was no apparent correlation between FIV status and CD8alpha chain reactivity. The relative isolation of Etosha from the other two parks could explain the marked difference in CD8alpha chain expression and suggests that lions similar to other mammalian species demonstrate polymorphic expression of the CD8alpha chain (197).}, number={3-4}, journal={VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY}, author={Bull, ME and Gebhard, DG and Tompkins, WAF and Kennedy-Stoskopf, S}, year={2002}, month={Jan}, pages={181–189} }
 @inproceedings{vahlenkamp_bull_dow_anderson_tompkins_tompkins_2001, title={B7.1/B7.2 and CTLA4 expression on feline T cells in vitro correlates with apoptosis}, number={2001}, booktitle={Journal of Leukocyte Biology}, author={Vahlenkamp, T. W. and Bull, M. E. and Dow, J. and Anderson, J. and Tompkins, M. B. and Tompkins, W. A. F.}, year={2001}, pages={255} }
 @article{ritchey_levy_bliss_tompkins_tompkins_2001, title={Constitutive expression of types 1 and 2 cytokines by alveolar macrophages from feline immunodeficiency virus-infected cats}, volume={79}, ISSN={["0165-2427"]}, DOI={10.1016/S0165-2427(01)00250-1}, abstractNote={Evidence suggests that feline immunodeficiency virus (FIV), causes pulmonary immunodeficiency. The overall objective of this study was to explore FIV-induced alterations in cell counts and cytokine gene expression in the pulmonary compartment during the acute stage infection. Bronchoalveolar lavage (BAL) cells were collected from FIV-infected and control cats at 0, 4, 10, and 16 weeks post-FIV infection for phenotype and cytokine analysis. The major change in BAL cellular populations following FIV-infection was the development of a neutrophilia. Total BAL cell counts and relative numbers of alveolar macrophages (AM), eosinophils, and lymphocytes remained similar in both groups. The RT-qcPCR analyses of AM purified from BAL showed constitutive expression of TNFα, IL6 and IL10 mRNAs that peaked during the acute stage of infection then declined. The TNFα and IL6 bioactive protein secretion showed a similar response. In contrast, IFNγ expression increased progressively with time after infection and paralleled a progressive increase in FIV-gag mRNA in AM. The IL12 p40 expression also differed from the other cytokines in that there was a progressive decrease in the number of cats with AM IL12 expression following FIV infection. Infection of AM in vitro with FIV also caused an increase in TNFα and IL6 mRNA and bioactive protein suggesting that the increased cytokine response by AM following infection of cats with FIV is an intrinsic characteristic of FIV-infected AM. In summary, pulmonary immune changes seen in FIV-infected cats are similar to those seen in HIV-infected human patients.}, number={1-2}, journal={VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY}, author={Ritchey, JW and Levy, JK and Bliss, SK and Tompkins, WAF and Tompkins, MB}, year={2001}, month={May}, pages={83–100} }
 @inproceedings{tompkins_bull_dow_tompkins_2001, title={Feline immunodeficiency virus (FIV) infection induces B7(+)CTLA4(+) T cell apoptosis: A model for T cell depletion and immunodeficiency}, number={2001}, booktitle={Journal of Leukocyte Biology}, author={Tompkins, M. B. and Bull, M. E. and Dow, J. L. and Tompkins, W. A. F.}, year={2001}, pages={254} }
 @misc{tompkins_tompkins_yang_2001, title={Nucleic acids obtained from the envelope coding region of feline immunodeficiency virus molecular clone designated JSY3}, volume={6,331,616}, number={2001 Dec. 18}, publisher={Washington, DC: U.S. Patent and Trademark Office}, author={Tompkins, W. A. and Tompkins, M. and Yang, J.-S.}, year={2001} }
 @inproceedings{bull_vahlenkamp_tompkins_tompkins_2001, title={T cell apoptosis in FIV-infected cats is blocked by the addition of antibodies to B7.1 and B7.2}, number={2001}, booktitle={Journal of Leukocyte Biology}, author={Bull, M. E. and Vahlenkamp, T. W. and Tompkins, M. B. and Tompkins, W. A. F.}, year={2001}, pages={256} }
 @article{harms_kennedy-stoskopf_horne_fuller_tompkins_2000, title={Cloning and sequencing hybrid striped bass (Morone saxatilis x M. chrysops) transforming growth factor-β (TGF-β), and development of a reverse transcription quantitative competitive polymerase chain reaction (RT-qcPCR) assay to measure TGF-β mRNA of teleost fish}, volume={10}, ISSN={1050-4648}, url={http://dx.doi.org/10.1006/fsim.1999.0230}, DOI={10.1006/fsim.1999.0230}, abstractNote={A transforming growth factor (TGF)-beta was isolated and cloned from hybrid striped bass (Morone saxatilis x M. chrysops) anterior kidney mononuclear cells. This isolate (Genbank accession number AF140363) contains an open reading frame of 1146 bases coding for a 382 amino acid protein most similar to rainbow trout TGF-beta (57.3 and 78.6% identity with precursor and active protein, respectively) and rat TGF-beta 1 (41.1 and 68.8% identity with precursor and active protein, respectively). Consensus primers were demonstrated to amplify specifically by polymerase chain reaction (PCR), a TGF-beta segment from 14 species of teleost fish comprising 10 taxonomic families in 7 orders. A reverse transcription quantitative competitive polymerase chain reaction (RT-qcPCR) assay was devised to measure TGF-beta mRNA expression in teleost fish. Higher levels of TGF-beta mRNA expression were detected in mononuclear cells of peripheral blood than from spleen or anterior kidney.}, number={1}, journal={Fish & Shellfish Immunology}, publisher={Elsevier BV}, author={Harms, C.A and Kennedy-Stoskopf, S and Horne, W.A and Fuller, F.J and Tompkins, W.A.F}, year={2000}, month={Jan}, pages={61–85} }
 @article{liang_hudson_levy_ritchey_tompkins_tompkins_2000, title={T cells overexpressing interferon-gamma and interleukin-10 are found in both the thymus and secondary lymphoid tissues of feline immunodeficiency virus-infected cats}, volume={181}, ISSN={["0022-1899"]}, DOI={10.1086/315226}, abstractNote={Similar to human immunodeficiency virus type 1, feline immunodeficiency virus (FIV) replicates in the thymus of infected animals, causing marked alteration in thymic lymphocyte subpopulations. The immune phenotype and cytokine patterns in the thymus and secondary lymphoid tissues of FIV-infected cats were investigated. FIV infection caused an acute-stage transient reduction in CD4CD8 double-positive thymocytes, a marked increase in CD8 single-positive thymocytes, and formation of thymic B cell lymphoid follicles. Interferon (IFN)-gamma and interleukin (IL)-10 mRNA were up-regulated in both the thymus and lymph nodes of FIV-infected cats. Analysis of purified CD4 and CD8 cells revealed that CD4 cells produced most of the IL-10, whereas IFN-gamma was produced by both subsets. Quantitative-competitive reverse-transcription polymerase chain reaction analysis revealed that thymocytes, especially CD4CD8 thymocytes, had much greater levels of gag mRNA than did lymph node T cells. Thus, overexpression of IFN-gamma and IL-10 is a feature of the thymus and secondary lymphoid tissues of FIV-infected cats.}, number={2}, journal={JOURNAL OF INFECTIOUS DISEASES}, author={Liang, YH and Hudson, LC and Levy, JK and Ritchey, JW and Tompkins, WAF and Tompkins, MB}, year={2000}, month={Feb}, pages={564–575} }
 @misc{tompkins_1999, title={Immunomodulation and therapeutic effects of the oral use of interferon-alpha: Mechanism of action}, volume={19}, ISSN={["1079-9907"]}, DOI={10.1089/107999099313325}, abstractNote={It is now well accepted that type 1 interferons (IFNs), IFN-alpha and IFN-beta, in addition to being molecules with powerful antiviral activity, play a critical role in modulating immune responses to foreign and self-antigens. This review of the literature documents the immunomodulatory effects of IFN-alpha and discusses its position and importance in the cytokine cascade. In addition, this review attempts to organize the literature describing local and systemic immunomodulatory effects of orally administered low doses of IFN-alpha, and provide a physiological explanation for the mechanism of action. Evidence suggests that, early in the process of antigen presentation to T helper (Th) cells, IFN-alpha derived principally from the antigen-presenting cells (APC) provides an important signal for Th precursor differentiation in favor of a Th1 immune response. IFN-alpha, perhaps via upregulation of the high-alphaffinity interleukin-12beta1/beta2 (IL-12beta1/beta2) receptor, renders Th1 cells responsive to IL-12 resulting in production of high levels of IFN-gamma crucial to the development of Th1 immune responses. In addition to being instrumental in the development of Th1 immune responses, IFN-alpha appears to be the major cytokine responsible for the amplification of the CD8+ T cell response and resistance to viral infections. Orally administered IFN-alpha induces similar Th1 cytokine responses in buccal mucosal lymph nodes (LN), including upregulation of IFN-gamma expression and downregulation of IL-4. Moreover, reports of systemic immune effects such as decreased autoimmune responses, increased antiviral and antibacterial responses, and generalized immune function changes after oral IFN-alpha administration are consistent with the known immunomodulatory role of IFN-alpha in a physiological setting. Responses to orally administered low doses of IFN-alpha also adhere to the principle of low-dose priming and high-dose anergy that dictates the cellular and cytokine responses to exogenously added cytokines both in vivo and in vitro. These observations collectively suggest that IFN-alpha administered to mucosal-associated immune tissue replicates the known physiological role of IFN-alpha, including regulation of CD4+ Th1 immunomodulatory cells and activation of CD8+ effector cells, which are both crucial to development of protective immune responses. What remains to be determined is how local mucosal immune responses to IFN-alpha given orally are translated into systemic immune responses and resistance to disease. This important question, the answer to which will have profound implications for new immunotherapies for immune-based diseases, is the focus of current research.}, number={8}, journal={JOURNAL OF INTERFERON AND CYTOKINE RESEARCH}, author={Tompkins, WA}, year={1999}, month={Aug}, pages={817–828} }
 @article{gebhard_dow_childers_alvelo_tompkins_tompkins_1999, title={Progressive expansion of an L-selectin-negative CD8 cell with anti-feline immunodeficiency virus (FIV) suppressor function in the circulation of FIV-infected cats}, volume={180}, ISSN={["0022-1899"]}, DOI={10.1086/315089}, abstractNote={The acute stage of feline immunodeficiency virus (FIV) infection is characterized by the appearance of a major CD8 subpopulation with reduced expression of the CD8 beta chain (CD8alpha+betalo). CD8 antiviral activity was subsequently shown to be mediated by the CD8alpha+betalo phenotype, which is the dominant CD8 phenotype in long-term infected cats. Two- and three-color flow cytometric analysis demonstrated that the CD8alpha+betalo subset is L-selectin negative (CD62L-) and has increased expression of CD44, CD49d, and CD18, consistent with an activation phenotype. The CD8alpha+betaloCD62L- cells but not the CD8alpha+betahiCD62L+ cells demonstrated strong antiviral activity in the FIV acute-infection assay. The progressive expansion of the CD8alpha+betaloCD62L- effector subset cells in FIV-infected cats parallels that seen in human immunodeficiency virus (HIV)-infected patients, suggesting that failure in homeostatic mechanisms regulating lymphocyte activation or trafficking (or both) may be a consequence of both HIV and FIV infections.}, number={5}, journal={JOURNAL OF INFECTIOUS DISEASES}, author={Gebhard, DH and Dow, JL and Childers, TA and Alvelo, JI and Tompkins, MB and Tompkins, WAF}, year={1999}, month={Nov}, pages={1503–1513} }
 @article{jordan_liang_hudson_tompkins_1999, title={Shedding of feline immunodeficiency virus in semen of domestic cats during acute infection}, volume={60}, number={2}, journal={American Journal of Veterinary Research}, author={Jordan, H. L. and Liang, Y. H. and Hudson, L. C. and Tompkins, W. A.}, year={1999}, pages={211–215} }
 @article{johnson_papadi_tompkins_sellon_orandle_bellah_bubenik_1998, title={Biphasic thymus response by kittens inoculated with feline immunodeficiency virus during fetal development}, volume={35}, ISSN={["0300-9858"]}, DOI={10.1177/030098589803500304}, abstractNote={The objective of this study was to assess the response of the feline thymus to fetal infection with feline immunodeficiency virus (FIV), an animal model for human immunodeficiency virus infection. Thirteen feline embryos from four litters were directly inoculated with FIV during the sixth week postbreeding, a period corresponding to the late second trimester of pregnancy. Thymus tissue was collected and analyzed from randomly selected kittens at 2, 4, and 16 weeks postinoculation (PI) and compared to age-matched control kittens that did not receive fetal inoculations. Of three kittens evaluated at 2 weeks PI (week 8 of gestation), neither thymus: body weight ratio nor histologic structure differed from five age-matched control animals. However, analysis of thymocyte subpopulations by flow cytometry revealed a significant ( P = 0.011) reduction in the percentage of cluster of differentiation (CD)4+/CD8+cells from an average of 66% in control fetuses to 45% in infected fetuses. FIV RNA transcription, assessed by in situ hybridization using an FIV gag RNA probe, was widely distributed throughout the thymus in patterns suggestive of both stromal and parenchymal infection. By 4 weeks PI (week 1 postpartum), the thymus: body weight ratio was significantly reduced ( P = 0.007) from 0.36% in five control kittens to 0.13% in four fetal inoculates. Severely atrophied thymus lobules supported minimal virus transcription and mean CD4+/CD8+thymocyte percentages were lower ( P = 0.021) in infected kittens (15%) compared to age-matched controls (66%). By 16 weeks PI (week 12 postpartum), thymus:body weight ratios of six inoculated kittens were not significantly different from six age-matched controls, suggesting that partial postnatal thymus regeneration had occurred. However, despite similar size, the regenerative thymus contained reduced percentages of CD4+/CD8+thymocytes (infected: 40% versus control: 76%; P = 0.009) and increased percentages of CD4+/CD8-(11% versus 5%; P = 0.002) and CD4-/CD8+(16% versus 9%; P = 0.035) lymphocytes. These changes were associated with widespread FIV transcription within thymic lymphocytes. Thus, the thymus of kittens infected with FIV during late fetal development is characterized by two distinct changes: neonatal atrophy and postnatal regeneration. Despite a recovery in thymus weight, thymus regeneration ineffectively restores the normal phenotypic distribution of thymocytes and supports FIV transcription.}, number={3}, journal={VETERINARY PATHOLOGY}, author={Johnson, CM and Papadi, GP and Tompkins, WA and Sellon, RK and Orandle, MS and Bellah, JR and Bubenik, LJ}, year={1998}, month={May}, pages={191–201} }
 @article{levy_ritchey_rottman_davidson_liang_jordan_tompkins_tompkins_1998, title={Elevated interleukin-10-to-interleukin-12 ratio in feline immunodeficiency virus-infected cats predicts loss of type 1 immunity to Toxoplasma gondii}, volume={178}, ISSN={["0022-1899"]}, DOI={10.1086/515632}, abstractNote={Similar to human immunodeficiency virus, feline immunodeficiency virus (FIV) induces immunodeficiency and enhanced susceptibility to secondary pathogens. To explore cytokine alterations in lentivirus immunodeficiency, constitutive mRNA expression was measured in lymph nodes of healthy and FIV-infected cats before and after challenge with Toxoplasma gondii. Cytokine mRNA expression was similar in control and FIV-infected cats during the first 10 weeks after infection. At 16 weeks, interferon (IFN)-gamma, tumor necrosis factor-alpha, and interleukin (IL)-10 mRNA were increased in FIV-infected cats. Challenge with T. gondii induced an increase in IL-2, IFN-gamma, and IL-12 in the lymph nodes of control cats, whereas IFN-gamma and IL-10 but not IL-2 or IL-12 increased in the lymph nodes of FIV-T. gondii coinfected cats. These results indicate that FIV immunodeficiency may derive from a failure to generate an IL-12-dependent type 1 response and that an elevated level of IL-10 mRNA expression is a predictor of lentivirus immunodeficiency.}, number={2}, journal={JOURNAL OF INFECTIOUS DISEASES}, author={Levy, JK and Ritchey, JW and Rottman, JB and Davidson, MG and Liang, YH and Jordan, HL and Tompkins, WA and Tompkins, MB}, year={1998}, month={Aug}, pages={503–511} }
 @article{jordan_howard_barr_kennedy-stoskopf_levy_tompkins_1998, title={Feline immunodeficiency virus is shed in semen from experimentally and naturally infected cats}, volume={14}, ISSN={["1931-8405"]}, DOI={10.1089/aid.1998.14.1087}, abstractNote={Although a laboratory isolate of feline immunodeficiency virus (FIV), FIV-NCSU1, has been transmitted by artificial insemination in domestic cats, transmission by naturally infected males during mating has not been reported. In order to determine whether virus shedding in semen is unique to the NCSU1 isolate, we analyzed electroejaculates from four specific-pathogen-free males infected with another laboratory strain, FIV-Petaluma, and eight random source males with naturally acquired infections. Seminal cell lysates from the cats infected with the Petaluma isolate were screened by nested polymerase chain reaction amplification for FIV gag DNA. Seminal cells and seminal plasma from these FIV-Petaluma cats were further analyzed for the presence of virus by cocultivation with a feline CD4+ T cell line and Crandell feline kidney cells. Electroejaculates from the naturally infected cats were cocultivated with the T cell line. Our results demonstrated that cell-free FIV was present in seminal plasma from two FIV-Petaluma cats and two naturally infected cats. Cell-associated seminal virus was detected in all of the FIV-Petaluma infected cats and one naturally infected cat. Secretion of viral gag p26 antigen, an indication of active viral replication, was evident in cocultures containing motile sperm purified by a swim-up procedure from a FIV-Petaluma cat. These results confirm that FIV shedding in semen is not restricted to a specific virus isolate. Furthermore, swim-up sperm from FIV-infected cats may be infectious in vitro.}, number={12}, journal={AIDS RESEARCH AND HUMAN RETROVIRUSES}, author={Jordan, HL and Howard, J and Barr, MC and Kennedy-Stoskopf, S and Levy, JK and Tompkins, WA}, year={1998}, month={Aug}, pages={1087–1092} }
 @article{jordan_howard_bucci_butterworth_english_kennedy-stoskopf_tompkins_tompkins_1998, title={Horizontal transmission of feline immunodeficiency virus with semen from seropositive cats}, volume={41}, DOI={10.1016/s0165-0378(98)00070-9}, abstractNote={The AIDS virus of cat species, feline immunodeficiency virus (FIV), has been used extensively as an animal model of HIV-1 infection. This felid lentivirus shares many molecular and biochemical traits with HIV-1 and causes similar immunologic and clinical perturbations, most notably CD4+ cell loss, impaired cell-mediated immunity and increased susceptibility to opportunistic pathogens. Previous reports have shown that FIV is transmitted horizontally by biting and vertically in utero and through nursing. Our objective was to determine whether FIV could be venereally transmitted in domestic cats. In the first experiment, susceptibility of the female reproductive tract to mucosal transmission of the FIV isolate, NCSU1, was demonstrated via intravaginal inoculation with infected cultured cells. We next identified virus in electroejaculates from asymptomatic, chronically FIV-NCSU1-infected, adult males. A fragment of FIV gag provirus DNA was detected by nested polymerase chain reaction (PCR) in nonfractionated seminal cells and in swim-up sperm preparations. Additionally, replication-competent virus was isolated from cell-free seminal plasma and seminal cells by co-cultivation with a feline CD4+ T-cell line. In the third study, queens were artificially inseminated via an intrauterine laparoscopic technique with electroejaculates from FIV-NCSU1-infected males. Of six inseminations carried out with fresh semen, three resulted in infection of queens. Lastly, immunohistochemical studies identified potential virus target cell populations in normal female reproductive tissues. In conclusion, these experiments indicate that FIV infection in domestic cats may provide a unique small animal model of sexual transmission of HIV-1.}, number={1-2}, journal={Journal of Reproductive Immunology}, author={Jordan, H. L. and Howard, J. G. and Bucci, J. G. and Butterworth, J. L. and English, R. and Kennedy-Stoskopf, S. and Tompkins, M. B. and Tompkins, W. A.}, year={1998}, pages={341–357} }
 @inbook{ritchey_tompkins_1998, title={Immunology of the cat: Nonspecific immunity in the cat}, booktitle={Handbook of vertebrate immunology}, publisher={San Diego: Academic Press}, author={Ritchey, J. W. and Tompkins, W. A. F.}, year={1998} }
 @article{elder_dean_hoover_hoxie_malim_mathes_neil_north_sparger_tompkins_et al._1998, title={Lessons from the cat: Feline immunodeficiency virus as a tool to develop intervention strategies against human immunodeficiency virus type 1}, volume={14}, ISSN={["0889-2229"]}, DOI={10.1089/aid.1998.14.797}, abstractNote={AIDS Research and Human RetrovirusesVol. 14, No. 9 Workshop Summary: Lessons from the Cat: Feline Immunodeficiency Virus as a Tool to Develop Intervention Strategies against Human Immunodeficiency Virus Type 1JOHN H. ELDER, GREGG A. DEAN, EDWARD A. HOOVER, JAMES A. HOXIE, MICHAEL H. MALIM, LAWRENCE MATHES, JAMES C. NEIL, THOMAS W. NORTH, ELLEN SPARGER, MARY B. TOMPKINS, WAYNE A.F. TOMPKINS, JANET YAMAMOTO, NAOYA YUHKI, NEILS C. PEDERSEN, and ROGER H. MILLERJOHN H. ELDERSearch for more papers by this author, GREGG A. DEANSearch for more papers by this author, EDWARD A. HOOVERSearch for more papers by this author, JAMES A. HOXIESearch for more papers by this author, MICHAEL H. MALIMSearch for more papers by this author, LAWRENCE MATHESSearch for more papers by this author, JAMES C. NEILSearch for more papers by this author, THOMAS W. NORTHSearch for more papers by this author, ELLEN SPARGERSearch for more papers by this author, MARY B. TOMPKINSSearch for more papers by this author, WAYNE A.F. TOMPKINSSearch for more papers by this author, JANET YAMAMOTOSearch for more papers by this author, NAOYA YUHKISearch for more papers by this author, NEILS C. PEDERSENSearch for more papers by this author, and ROGER H. MILLERSearch for more papers by this authorPublished Online:15 Mar 2009https://doi.org/10.1089/aid.1998.14.797AboutSectionsPDF/EPUB ToolsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail FiguresReferencesRelatedDetailsCited ByEqual contributions of feline immunodeficiency virus and coinfections to morbidity in African lionsInternational Journal for Parasitology: Parasites and Wildlife, Vol. 16Pathogenesis of oral FIV infection21 September 2017 | PLOS ONE, Vol. 12, No. 9Structural features of the C8 antiviral peptide in a membrane-mimicking environmentBiochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 1838, No. 3Accessory Genes Confer a High Replication Rate to Virulent Feline Immunodeficiency VirusJournal of Virology, Vol. 87, No. 14In Vivo Assessment of Natural Killer Cell Responses during Chronic Feline Immunodeficiency Virus Infection31 May 2012 | PLoS ONE, Vol. 7, No. 5FIV diversity: FIVPle 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Immunodeficiency Virus Molecular Clone FIV-PPR DNA InoculationJAIDS Journal of Acquired Immune Deficiency Syndromes, Vol. 23, No. 1Site-specific Incorporation of Nucleoside Analogs by HIV-1 Reverse Transcriptase and the Template Grip Mutant P157SJournal of Biological Chemistry, Vol. 275, No. 1AIDS vaccination studies using feline immunodeficiency virus as a model: immunisation with inactivated whole virus suppresses viraemia levels following intravaginal challenge with infected cells but not following intravenous challenge with cell-free virusVaccine, Vol. 18, No. 1-2Cyanovirin-N Binds to gp120 To Interfere with CD4-Dependent Human Immunodeficiency Virus Type 1 Virion Binding, Fusion, and Infectivity but Does Not Affect the CD4 Binding Site on gp120 or Soluble CD4-Induced Conformational Changes in gp120Journal of Virology, Vol. 73, No. 5 Volume 14Issue 9Jun 1998 To cite this article:JOHN H. ELDER, GREGG A. DEAN, EDWARD A. HOOVER, JAMES A. HOXIE, MICHAEL H. MALIM, LAWRENCE MATHES, JAMES C. NEIL, THOMAS W. NORTH, ELLEN SPARGER, MARY B. TOMPKINS, WAYNE A.F. TOMPKINS, JANET YAMAMOTO, NAOYA YUHKI, NEILS C. PEDERSEN, and ROGER H. MILLER.Workshop Summary: Lessons from the Cat: Feline Immunodeficiency Virus as a Tool to Develop Intervention Strategies against Human Immunodeficiency Virus Type 1.AIDS Research and Human Retroviruses.Jun 1998.797-801.http://doi.org/10.1089/aid.1998.14.797Published in Volume: 14 Issue 9: March 15, 2009PDF download}, number={9}, journal={AIDS RESEARCH AND HUMAN RETROVIRUSES}, author={Elder, JH and Dean, GA and Hoover, EA and Hoxie, JA and Malim, MH and Mathes, L and Neil, JC and North, TW and Sparger, E and Tompkins, MB and et al.}, year={1998}, month={Jun}, pages={797–801} }
 @article{bucci_english_jordan_childers_tompkins_tompkins_1998, title={Mucosally transmitted feline immunodeficiency virus induces a CD8(+) antiviral response that correlates with reduction of cell-associated virus}, volume={177}, ISSN={["0022-1899"]}, DOI={10.1086/513822}, abstractNote={Intravaginal inoculation of cats with feline immunodeficiency virus (FIV) results in acute systemic infection accompanied by a strong CD8+ immune response that inhibits viral replication. CD8+ anti-FIV activity, revealed by increased FIV replication in peripheral blood mononuclear cells (PBMC) depleted of CD8+ lymphocytes, was detected by 6 weeks after inoculation and correlated with reduced PBMC-associated virus at 12, 16, and 32 weeks after inoculation. Some cats with strong CD8+ anti-FIV activity during acute infection did not seroconvert and yielded no evidence of FIV infection at later times. These data suggest that CD8+ immunity may play a major role in eliminating virus during primary transmucosal FIV infection and may down-regulate viral replication during asymptomatic infection.}, number={1}, journal={JOURNAL OF INFECTIOUS DISEASES}, author={Bucci, JG and English, RV and Jordan, HL and Childers, TA and Tompkins, MB and Tompkins, WAF}, year={1998}, month={Jan}, pages={18–25} }
 @article{bucci_gebhard_childers_english_tompkins_tompkins_1998, title={The CD8(+) cell phenotype mediating antiviral activity in feline immunodeficiency virus-infected cats is characterized by reduced surface expression of the CD8 beta chain}, volume={178}, ISSN={["0022-1899"]}, DOI={10.1086/515699}, abstractNote={The acute stage of feline immunodeficiency virus (FIV) infection is characterized by a CD8+ anti-FIV response that parallels the appearance of a CD8+ subpopulation with reduced expression of the beta chain (CD8 alpha + beta lo). The relationship between the CD8 alpha + beta lo phenotype and CD8+ anti-FIV activity was examined. Flow cytometric analysis of peripheral blood mononuclear cells with anti-CD8 beta chain monoclonal antibody 117 revealed that the CD8 alpha + beta lo phenotype expanded throughout the asymptomatic infection, constituting 80%-90% of the CD8 beta + cells in long-term-infected cats. Purified CD8 alpha + beta hi and CD8 alpha + beta lo subpopulations were analyzed for anti-FIV activity in an acute infection assay. Anti-FIV activity resided principally in the CD8 alpha + beta lo population and was demonstrated in acute FIV infections, as well as in long-term asymptomatic infections. These data suggest that a unique CD8 alpha + beta lo anti-FIV phenotype arises early in infection and may play a major role in eliminating virus and maintaining the asymptomatic infection.}, number={4}, journal={JOURNAL OF INFECTIOUS DISEASES}, author={Bucci, JG and Gebhard, DH and Childers, TA and English, RV and Tompkins, MB and Tompkins, WAF}, year={1998}, month={Oct}, pages={968–977} }
 @misc{tompkins_tompkins_1997, title={Feline immunodeficiency virus isolate NCSU.sub.1}, volume={5,665,592}, number={1997 Sept. 9}, publisher={Washington, DC: U.S. Patent and Trademark Office}, author={Tompkins, W. A. F. and Tompkins, M. B.}, year={1997} }
 @misc{tompkins_tompkins_1995, title={Feline immunodeficiency virus isolate NCSU.sub.1Lb}, volume={5413927}, publisher={Washington, DC: U.S. Patent and Trademark Office}, author={Tompkins, W. A. F. and Tompkins, M. B.}, year={1995} }