@article{womble_weingart_may_garner_luff_2024, title={A putatively novel papillomavirus associated with cutaneous plaques and squamous cell carcinoma in captive North American snow leopards (<i>Panthera uncia</i>)}, ISSN={["1544-2217"]}, DOI={10.1177/03009858241254340}, abstractNote={Cutaneous plaques and squamous cell carcinoma (SCC) are common in captive North American snow leopards (SLs) (}, journal={VETERINARY PATHOLOGY}, author={Womble, Mandy and Weingart, Shaina and May, Susan and Garner, Michael and Luff, Jennifer}, year={2024}, month={May} }
 @article{luff_weingart_may_murphy_2023, title={A subset of equine oral squamous cell carcinomas is associated with Equus caballus papillomavirus 2 infection}, volume={205}, ISSN={["1532-3129"]}, DOI={10.1016/j.jcpa.2023.06.003}, abstractNote={The aetiology of oral squamous cell carcinoma (SCC) in horses is unknown, but papillomavirus infection as well as chronic periodontal disease are suspected to play a pathogenic role. In humans, some oropharyngeal cancers develop in association with human papillomaviruses. Equus caballus papillomavirus 2 (EcPV2) is suspected to play a causal role in the development of equine genital SCC. Given that association, we hypothesized that EcPV2 is associated with the development of oral SCC in horses. We performed standard polymerase chain reaction (PCR) and in-situ hybridization (ISH) for EcPV2 on 31 formalin-fixed paraffin-embedded equine oral SCCs (lingual, gingival, palate) and 10 equine non-SCC oral samples. PCR for EcPV2 was positive in 10/31 (32%) oral SCCs while all non-SCC oral samples were negative. Intense hybridization signals for EcPV2 nucleic acid were detected by ISH within neoplastic epithelial cells in 8/31 (26%) oral SCCs but not in the adjacent normal oral mucosa. No hybridization signals were detected within control samples. This study provides additional support for a pathogenic association of EcPV2 in oral SCC in horses.}, journal={JOURNAL OF COMPARATIVE PATHOLOGY}, author={Luff, Jennifer and Weingart, Shaina and May, Susan and Murphy, Brian}, year={2023}, month={Aug}, pages={1–6} }
 @article{resendes_trainor_bera_cheng_luff_2023, title={Claw bed inverted squamous papilloma associated with canine papillomavirus type 2 in a dog}, ISSN={["1365-3164"]}, DOI={10.1111/vde.13208}, abstractNote={AbstractA claw bed inverted squamous papilloma (ISP) presented clinically as a swollen digit in a dog. Canine papillomavirus (CPV) type 2 was amplified by PCR and localised to the papilloma's epidermis using in situ hybridisation. This is the first report demonstrating a claw bed ISP caused by CPV.}, journal={VETERINARY DERMATOLOGY}, author={Resendes, Ana R. and Trainor, Karen E. and Bera, Monali and Cheng, Ryan Chuang Fu and Luff, Jennifer}, year={2023}, month={Oct} }
 @misc{munday_knight_luff_2022, title={Papillomaviral skin diseases of humans, dogs, cats and horses: A comparative review. Part 1: Papillomavirus biology and hyperplastic lesions}, volume={288}, ISSN={["1532-2971"]}, DOI={10.1016/j.tvjl.2022.105897}, abstractNote={Papillomaviruses (PVs) cause disease in humans, dogs, cats, and horses. While there are some differences, many aspects of the pathogenesis, presentation, and treatment of these diseases are similar between the four species. In this review, the PV-induced diseases of humans are compared to the similar diseases that develop in the companion animal species. By comparing with the human diseases, it is possible to make assumptions about some of the less common and less well-studied diseases in the veterinary species. In the first part of this review, the PV lifecycle is discussed along with the classification of PVs and the immune response to PV infection. The hyperplastic diseases caused by PVs are then discussed; including PV-induced cutaneous, anogenital, and oral warts within the four species.}, journal={VETERINARY JOURNAL}, author={Munday, John S. and Knight, Cameron G. and Luff, Jennifer A.}, year={2022}, month={Oct} }
 @misc{munday_knight_luff_2022, title={Papillomaviral skin diseases of humans, dogs, cats and horses: A comparative review. Part 2: Pre-neoplastic and neoplastic diseases}, volume={288}, ISSN={["1532-2971"]}, DOI={10.1016/j.tvjl.2022.105898}, abstractNote={Papillomaviruses (PVs) are well recognized to cause pre-neoplastic and neoplastic diseases in humans. Similarly, there is increasing evidence that PVs play a significant role in the development of pre-neoplastic and neoplastic diseases of the haired skin of dogs and cats, and the mucosa of horses. As the mechanisms by which PVs cause neoplasia are well studied in humans, it is valuable to compare the PV-induced neoplasms of humans with similar PV-associated neoplasms in the companion animal species. In the second part of this comparative review, the pre-neoplastic and neoplastic diseases thought to be caused by PVs in humans, dogs, cats, and horses are described. This includes PV-induced cutaneous plaques, cutaneous squamous cell carcinomas (SCCs) and mucosal SCCs within the four species. The review concludes with a discussion about the potential use of vaccines to prevent PV-induced diseases of dogs, cats, and horses.}, journal={VETERINARY JOURNAL}, author={Munday, John S. and Knight, Cameron G. and Luff, Jennifer A.}, year={2022}, month={Oct} }
 @article{quinlan_may_weeks_yuan_luff_2021, title={Canine Papillomavirus 2 E6 Does Not Interfere With UVB-Induced Upregulation of p53 and p53-Regulated Genes}, volume={8}, ISSN={["2297-1769"]}, DOI={10.3389/fvets.2021.570982}, abstractNote={Cutaneous papillomaviruses are oncogenic viruses that cause severe, persistent infections that can develop into skin cancers within ultraviolet (UV)-exposed skin of immunodeficient individuals, such as those with X-linked severe combined immunodeficiency (XSCID). A canine research model of XSCID exhibits a similar phenotype; these dogs develop severe canine papillomavirus 2 (CPV2) infections that often progress to cancer. Thus, the dog is a natural, spontaneous model to investigate cutaneous papillomavirus infections in immunodeficient patients. The human papillomavirus oncogene E6 contributes to cancer development, in part, by initiating degradation of the tumor suppressor protein p53, or by inhibiting upregulation of p53-dependent genes required within the cell growth arrest and apoptotic pathways, thereby leading to an accumulation of DNA damage required for oncogenesis. Currently, little is known about CPV2, and how it promotes cancer development. The aim of this study was to determine if CPV2 oncogene E6 similarly affects p53 upon activation by UV radiation, as well as the downstream p53-regulated genes necessary to control growth arrest and apoptosis. We determined that cutaneous CPV2 E6 does not degrade p53, or interfere with the upregulation of p53-regulated genes p21, Bax, Bak, or lncRNA-p21, suggesting that CPV2 may use a p53-independent mechanism to contribute to oncogenesis.}, journal={FRONTIERS IN VETERINARY SCIENCE}, author={Quinlan, Sarah and May, Susan and Weeks, Ryan and Yuan, Hang and Luff, Jennifer}, year={2021}, month={Mar} }
 @article{stewart_schaaf_luff_freund_becker_tufts_robertson_gonzalez_2021, title={HOPX+ injury-resistant intestinal stem cells drive epithelial recovery after severe intestinal ischemia}, volume={321}, ISSN={["1522-1547"]}, url={https://doi.org/10.1152/ajpgi.00165.2021}, DOI={10.1152/ajpgi.00165.2021}, abstractNote={ This paper supports that rISCs are resistant to ischemic injury and likely an important source of cellular renewal following near-complete epithelial loss. Furthermore, we have evidence that HOPX controls ISC activity state and may be a critical signaling pathway during ISC-mediated repair. Finally, we use multiple novel methods to evaluate ISCs in a translationally relevant large animal model of severe intestinal injury and provide evidence for the potential role of rISCs as therapeutic targets. }, number={5}, journal={AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY}, publisher={American Physiological Society}, author={Stewart, Amy Stieler and Schaaf, Cecilia Renee and Luff, Jennifer A. and Freund, John M. and Becker, Thomas C. and Tufts, Sara R. and Robertson, James B. and Gonzalez, Liara M.}, year={2021}, month={Oct}, pages={G588–G602} }
 @article{deming_wellehan_colegrove_hall_luff_lowenstine_duignan_cortes-hinojosa_gulland_2021, title={Unlocking the Role of a Genital Herpesvirus, Otarine Herpesvirus 1, in California Sea Lion Cervical Cancer}, volume={11}, ISSN={["2076-2615"]}, DOI={10.3390/ani11020491}, abstractNote={Urogenital carcinoma in California sea lions (Zalophus californianus) is the most common cancer of marine mammals. Primary tumors occur in the cervix, vagina, penis, or prepuce and aggressively metastasize resulting in death. This cancer has been strongly associated with a sexually transmitted herpesvirus, otarine herpesvirus 1 (OtHV1), but the virus has been detected in genital tracts of sea lions without cancer and a causative link has not been established. To determine if OtHV1 has a role in causing urogenital carcinoma we sequenced the viral genome, quantified viral load from cervical tissue from sea lions with (n = 95) and without (n = 163) urogenital carcinoma, and measured viral mRNA expression using in situ mRNA hybridization (Basescope®) to quantify and identify the location of OtHV1 mRNA expression. Of the 95 sea lions diagnosed with urogenital carcinoma, 100% were qPCR positive for OtHV1, and 36% of the sea lions with a normal cervix were positive for the virus. The non-cancer OtHV1 positive cases had significantly lower viral loads in their cervix compared to the cervices from sea lions with urogenital carcinoma. The OtHV1 genome had several genes similar to the known oncogenes, and RNA in situ hybridization demonstrated high OtHV1 mRNA expression within the carcinoma lesions but not in normal cervical epithelium. The high viral loads, high mRNA expression of OtHV1 in the cervical tumors, and the presence of suspected OtHV1 oncogenes support the hypothesis that OtHV1 plays a significant role in the development of sea lion urogenital carcinoma.}, number={2}, journal={ANIMALS}, author={Deming, Alissa C. and Wellehan, James F. X. and Colegrove, Kathleen M. and Hall, Ailsa and Luff, Jennifer and Lowenstine, Linda and Duignan, Padraig and Cortes-Hinojosa, Galaxia and Gulland, Frances M. D.}, year={2021}, month={Feb} }
 @article{alloway_linder_may_rose_delay_bender_tucker_luff_2020, title={A Subset of Equine Gastric Squamous Cell Carcinomas Is Associated With Equus Caballus Papillomavirus-2 Infection}, volume={57}, ISSN={["1544-2217"]}, DOI={10.1177/0300985820908797}, abstractNote={ Squamous cell carcinoma (SCC) is the most common neoplasm of the equine stomach. However, the mechanisms underlying malignant transformation are unknown. As Equus caballus papillomavirus–2 (EcPV-2) is a likely cause of some genital SCCs, we hypothesized that EcPV-2 is associated with a subset of equine gastric SCCs. To this aim, we performed polymerase chain reaction (PCR) and in situ hybridization (ISH) for EcPV-2 E6/ E7 oncogenes on 11 gastric SCCs and on gastric samples from 15 control horses with no SCC. PCR for EcPV-2 was positive in 7/11 (64%) gastric SCCs; non-SCC gastric samples were all negative. Intense hybridization signals for EcPV-2 E6/E7 nucleic acid were detected by ISH within tumor cells in 5/11 (45%) gastric SCCs, including distant metastases. No hybridization signals were detected within any of the non-SCC gastric cases. This study provides support for a potential association between EcPV-2 infection and a subset of equine gastric SCC. }, number={3}, journal={VETERINARY PATHOLOGY}, author={Alloway, Elizabeth and Linder, Keith and May, Susan and Rose, Trevor and DeLay, Josepha and Bender, Susan and Tucker, Alison and Luff, Jennifer}, year={2020}, month={May}, pages={427–431} }
 @article{quinlan_may_weeks_yuan_luff_2020, title={Abrogation of Constitutive and Induced Type I and Type III Interferons and Interferon-Stimulated Genes in Keratinocytes by Canine Papillomavirus 2 E6 and E7}, volume={12}, ISSN={["1999-4915"]}, DOI={10.3390/v12060677}, abstractNote={Cutaneous papillomaviruses can cause severe, persistent infections and skin cancer in immunodeficient patients, including people with X-linked severe combined immunodeficiency (XSCID). A similar phenotype is observed in a canine model of XSCID; these dogs acquire severe cutaneous papillomavirus infections that can progress to cancer in association with canine papillomavirus type 2 (CPV2). This canine model system provides a natural spontaneous animal model for investigation of papillomavirus infections in immunodeficient patients. Currently, it is unknown if CPV2 can subvert the innate immune system and interfere with its ability to express antiviral cytokines, which are critical in the host defense against viral pathogens. The aim of the current study was to determine if the oncogenes E6 and E7 from CPV2 interfere with expression of antiviral cytokines in keratinocytes, the target cells of papillomavirus infections. We determined that E6 but not E7 interferes with the constitutive expression of some antiviral cytokines, including interferon (IFN)-β and the IFN-stimulated gene IFIT1. Both E6 and E7 interfere with the transcriptional upregulation of the antiviral cytokines in response to stimulation with the dsDNA Poly(dA:dT). In contrast, while E6 also interferes with the transcriptional upregulation of antiviral cytokines in response to stimulation with the dsRNA Poly(I:C), E7 interferes with only a subset of these antiviral cytokines. Finally, we demonstrated that E7 but not E6 abrogates signaling through the type I IFN receptor. Taken together, CPV2 E6 and E7 both impact expression of antiviral cytokines in canine keratinocytes, albeit likely through different mechanisms.}, number={6}, journal={VIRUSES-BASEL}, author={Quinlan, Sarah and May, Susan and Weeks, Ryan and Yuan, Hang and Luff, Jennifer A.}, year={2020}, month={Jun} }
 @article{baja_lewbart_luff_nolan_2020, title={Unexpected but transient tumour enlargement preceded complete regression and long-term control after irradiation of squamous cell carcinoma in a red-eared slider (Trachemys scripta elegans)}, volume={8}, ISSN={["2052-6121"]}, DOI={10.1136/vetreccr-2019-001039}, abstractNote={A red‐eared slider with a chronic non‐healing ulcerative shell lesion was diagnosed with cutaneous squamous cell carcinoma (SCC). The animal underwent surgical debulking and adjuvant hypofractionated radiation therapy. The lesion initially responded, with near‐complete tumour regression, but then began growing again just a few months after finishing radiotherapy. Then, after several months with no additional tumour‐directed therapy, the lesion again regressed. Five years post‐irradiation and with no further treatment, the turtle now remains tumour‐free. This unusual pattern of disease regression, followed by transient growth and then long‐term local tumour control, suggests either a spontaneous remission or a pseudoprogression‐like phenomenon. Careful clinical follow‐up and reporting of future cases will aid in determining whether this pseudoprogression‐like event was random, versus being a common component of the chelonian response to irradiation of cutaneous SCC.}, number={2}, journal={VETERINARY RECORD CASE REPORTS}, author={Baja, Alexie J. and Lewbart, Gregory A. and Luff, Jennifer A. and Nolan, Michael W.}, year={2020}, month={Jun} }
 @article{luff_mader_rowland_britton_fass_yuan_2019, title={Viral genome integration of canine papillomavirus 16}, volume={7}, ISSN={["2405-8521"]}, DOI={10.1016/j.pvr.2019.02.002}, abstractNote={Papillomaviruses infect humans and animals, most often causing benign proliferations on skin or mucosal surfaces. Rarely, these infections persist and progress to cancer. In humans, this transformation most often occurs with high-risk papillomaviruses, where viral integration is a critical event in carcinogenesis. The first aim of this study was to sequence the viral genome of canine papillomavirus (CPV) 16 from a pigmented viral plaque that progressed to metastatic squamous cell carcinoma in a dog. The second aim was to characterize multiple viral genomic deletions and translocations as well as host integration sites. The full viral genome was identified using a combination of PCR and high throughput sequencing. CPV16 is most closely related to chipapillomaviruses CPV4, CPV9, and CPV12 and we propose CPV16 be classified as a chipapillomavirus. Assembly of the full viral genome enabled identification of deletion of portions of the E1 and E2/E4 genes and two viral translocations within the squamous cell carcinoma. Genome walking was performed which identified four sites of viral integration into the host genome. This is the first description of integration of a canine papillomavirus into the host genome, raising the possibility that CPV16 may be a potential canine high-risk papillomavirus type.}, journal={PAPILLOMAVIRUS RESEARCH}, author={Luff, Jennifer and Mader, Michelle and Rowland, Peter and Britton, Monica and Fass, Joseph and Yuan, Hang}, year={2019}, month={Jun}, pages={88–96} }
 @article{luff_burns_mader_priest_tuttle_2018, title={Cutaneous squamous cell carcinoma associated with Zalophus californianus papillomavirus 1 in a California sea lion}, volume={30}, ISSN={["1943-4936"]}, DOI={10.1177/1040638718769702}, abstractNote={ Papillomaviruses (PVs) are found in many species and infect epithelial cells at both mucosal and cutaneous sites. PVs are generally species-specific and cause benign epithelial proliferations, often forming papillomas or plaques. Rarely, these infections can persist, allowing progression to in situ and invasive cancers. We describe herein a case of multiple cutaneous pigmented plaques from a California sea lion ( Zalophus californianus) that progressed to in situ and invasive squamous cell carcinoma (SCC). The lesions were characterized by epithelial hyperplasia, hyperkeratosis, and hypergranulosis that bordered more dysplastic areas, and, at one site, bordered an invasive SCC. Immunohistochemistry for papillomavirus antigen revealed strong nuclear immunoreactivity within keratinocytes in the hyperplastic epidermis. PCR was performed using degenerate and specific primers to detect papillomavirus DNA. Specific primers were used to amplify Zalophus californianus papillomavirus 1 (ZcPV-1), the only sea lion papillomavirus known to date. We detected ZcPV-1 DNA within the pigmented plaque, and in both in situ and invasive SCC samples. }, number={4}, journal={JOURNAL OF VETERINARY DIAGNOSTIC INVESTIGATION}, author={Luff, Jennifer A. and Burns, Rachel E. and Mader, Michelle and Priest, Kara D. and Tuttle, Allison D.}, year={2018}, month={Jul}, pages={572–575} }
 @article{linder_bizikova_luff_zhou_yuan_breuhaus_nelson_mackay_2018, title={Generalized papillomatosis in three horses associated with a novel equine papillomavirus (EcPV8)}, volume={29}, number={1}, journal={Veterinary Dermatology}, author={Linder, K. E. and Bizikova, P. and Luff, J. and Zhou, D. and Yuan, H. and Breuhaus, B. and Nelson, E. and Mackay, R.}, year={2018} }
 @article{hoggard_munday_luff_2018, title={Localization of Felis catus Papillomavirus Type 2 E6 and E7 RNA in Feline Cutaneous Squamous Cell Carcinoma}, volume={55}, ISSN={["1544-2217"]}, DOI={10.1177/0300985817750456}, abstractNote={ Findings from polymerase chain reaction–based methods have suggested a role of Felis catus papillomavirus 2 (FcaPV-2) in the development of feline cutaneous squamous cell carcinoma (SCC). However, because polymerase chain reaction cannot localize deoxyribonucleic acid or ribonucleic acid within the lesion, it is difficult to differentiate a coincidental FcaPV-2 infection and a causative association. Given that a key event in the pathogenesis of human papillomavirus–induced cancer is the expression of viral E6 and E7 oncogenes, localization of FcaPV-2 E6 and E7 transcription within neoplastic cells in feline SCCs would support a causative role for this papillomavirus. Therefore, RNAscope in situ hybridization was used to localize FcaPV-2 E6 and E7 transcripts in 18 formalin-fixed paraffin-embedded samples of cutaneous SCC. Positive signals were present within 5 of 9 samples (56%) from ultraviolet-protected sites and 0 of 9 samples from ultraviolet-exposed sites. In the 4 in situ hybridization–positive samples that contained adjacent hyperplastic skin, hybridization patterns in these regions were characterized by intense nuclear signals within the superficial epidermis and punctate signals within the basal epithelial layers. However, within the 5 SCCs, punctate signals were present within all layers of the epidermis, with progressive loss of intense nuclear signals within the superficial epidermis. This hybridization pattern is consistent with unregulated E6 and E7 transcription and decreased viral replication and is similar to the pattern observed in human papillomavirus–induced cancers as they progress from hyperplastic lesions containing productive infections to nonproductive neoplasms. These findings support a causative role for FcaPV-2 in the pathogenesis of feline SCC. }, number={3}, journal={VETERINARY PATHOLOGY}, author={Hoggard, Nathan and Munday, John S. and Luff, Jennifer}, year={2018}, month={May}, pages={409–416} }
 @article{alkhilaiwi_wang_zhou_raudsepp_ghosh_paul_palechor-ceron_brandt_luff_liu_et al._2018, title={Long-term expansion of primary equine keratinocytes that maintain the ability to differentiate into stratified epidermis}, volume={9}, ISSN={["1757-6512"]}, DOI={10.1186/s13287-018-0918-x}, abstractNote={Skin injuries in horses frequently lead to chronic wounds that lack a keratinocyte cover essential for healing. The limited proliferation of equine keratinocytes using current protocols has limited their use for regenerative medicine. Previously, equine induced pluripotent stem cells (eiPSCs) have been produced, and eiPSCs could be differentiated into equine keratinocytes suitable for stem cell-based skin constructs. However, the procedure is technically challenging and time-consuming. The present study was designed to evaluate whether conditional reprogramming (CR) could expand primary equine keratinocytes rapidly in an undifferentiated state but retain their ability to differentiate normally and form stratified epithelium.Conditional reprogramming was used to isolate and propagate two equine keratinocyte cultures. PCR and FISH were employed to evaluate the equine origin of the cells and karyotyping to perform a chromosomal count. FACS analysis and immunofluorescence were used to determine the purity of equine keratinocytes and their proliferative state. Three-dimensional air-liquid interphase method was used to test the ability of cells to differentiate and form stratified squamous epithelium.Conditional reprogramming was an efficient method to isolate and propagate two equine keratinocyte cultures. Cells were propagated at the rate of 2.39 days/doubling for more than 40 population doublings. A feeder-free culture method was also developed for long-term expansion. Rock-inhibitor is critical for both feeder and feeder-free conditions and for maintaining the proliferating cells in a stem-like state. PCR and FISH validated equine-specific markers in the cultures. Karyotyping showed normal equine 64, XY chromosomes. FACS using pan-cytokeratin antibodies showed a pure population of keratinocytes. When ROCK inhibitor was withdrawn and the cells were transferred to a three-dimensional air-liquid culture, they formed a well-differentiated stratified squamous epithelium, which was positive for terminal differentiation markers.Our results prove that conditional reprogramming is the first method that allows for the rapid and continued in vitro propagation of primary equine keratinocytes. These unlimited supplies of autologous cells could be used to generate transplants without the risk of immune rejection. This offers the opportunity for treating recalcitrant horse wounds using autologous transplantation.}, journal={STEM CELL RESEARCH & THERAPY}, author={Alkhilaiwi, Faris and Wang, Liqing and Zhou, Dan and Raudsepp, Terje and Ghosh, Sharmila and Paul, Siddartha and Palechor-Ceron, Nancy and Brandt, Sabine and Luff, Jennifer and Liu, Xuefeng and et al.}, year={2018}, month={Jul} }
 @misc{munday_thomson_luff_2017, title={Papillomaviruses in dogs and cats}, volume={225}, ISSN={["1532-2971"]}, DOI={10.1016/j.tvjl.2017.04.018}, abstractNote={Papillomaviruses (PVs) cause disease in both dogs and cats. In dogs, PVs are thought to cause oral papillomatosis, cutaneous papillomas and canine viral pigmented plaques, whereas PVs have been rarely associated with the development of oral and cutaneous squamous cell carcinomas in this species. In cats, PVs are currently thought to cause oral papillomas, feline viral plaques, Bowenoid in situ carcinomas and feline sarcoids. Furthermore, there is increasing evidence that PVs may also be a cause of cutaneous squamous cell carcinomas and basal cell carcinomas in cats. These diseases are discussed in this review. Additionally, there is a brief overview of PV biology, including how these viruses cause disease. Diagnostic techniques and possible methods to prevent PV infection are also discussed.}, journal={VETERINARY JOURNAL}, author={Munday, John S. and Thomson, Neroli A. and Luff, Jennifer A.}, year={2017}, month={Jul}, pages={23–31} }
 @article{luff_yuan_suter_müller_schlegel_moore_2013, title={Canine keratinocytes upregulate type I interferons and proinflammatory cytokines in response to poly(dA:dT) but not to canine papillomavirus}, volume={153}, ISSN={0165-2427}, url={http://dx.doi.org/10.1016/J.VETIMM.2013.02.001}, DOI={10.1016/J.VETIMM.2013.02.001}, abstractNote={Papillomaviruses (PV) are double stranded (ds) DNA viruses that infect epithelial cells within the skin or mucosa, most often causing benign neoplasms that spontaneously regress. The immune system plays a key role in the defense against PVs. Since these viruses infect keratinocytes, we wanted to investigate the role of the keratinocyte in initiating an immune response to canine papillomavirus-2 (CPV-2) in the dog. Keratinocytes express a variety of pattern recognition receptors (PRR) to distinguish different cutaneous pathogens and initiate an immune response. We examined the mRNA expression patterns for several recently described cytosolic nucleic acid sensing PRRs in canine monolayer keratinocyte cultures using quantitative reverse transcription-polymerase chain reaction. Unstimulated normal cells were found to express mRNA for melanoma differentiation associated gene 5 (MDA5), retinoic acid-inducible gene I (RIG-I), DNA-dependent activation of interferon regulatory factors, leucine rich repeat flightless interacting protein 1, and interferon inducible gene 16 (IFI16), as well as their adaptor molecules myeloid differentiation primary response gene 88, interferon-β promoter stimulator 1, and endoplasmic reticulum-resident transmembrane protein stimulator of interferon genes. When stimulated with synthetic dsDNA [poly(dA:dT)] or dsRNA [poly(I:C)], keratinocytes responded with increased mRNA expression levels for interleukin-6, tumor necrosis factor-α, interferon-β, RIG-I, IFI16, and MDA5. There was no detectable increase in mRNA expression, however, in keratinocytes infected with CPV-2. Furthermore, CPV-2-infected keratinocytes stimulated with poly(dA:dT) and poly(I:C) showed similar mRNA expression levels for these gene products when compared with expression levels in uninfected cells. These results suggest that although canine keratinocytes contain functional PRRs that can recognize and respond to dsDNA and dsRNA ligands, they do not appear to recognize or initiate a similar response to CPV-2.}, number={3-4}, journal={Veterinary Immunology and Immunopathology}, publisher={Elsevier BV}, author={Luff, Jennifer A. and Yuan, Hang and Suter, Maja M. and Müller, Eliane J. and Schlegel, Richard and Moore, Peter F.}, year={2013}, month={Jun}, pages={177–186} }