@article{liu_hudson_tompkins_vahlenkamp_colby_rundle_meeker_2006, title={Cerebrospinal fluid is an efficient route for establishing brain infection with feline immunodeficiency virus and transfering infectious virus to the periphery}, volume={12}, ISSN={["1538-2443"]}, DOI={10.1080/13550280600889567}, abstractNote={Like human immunodeficiency virus (HIV), feline immunodeficiency virus (FIV) invades and infects the central nervous system (CNS) soon after peripheral infection. The appearance of viral RNA is particularly prominent in the cerebrospinal fluid (CSF), suggesting an efficient route of virus transfer across the blood-CSF barrier. This raises the concern whether this route can establish a stable viral reservoir and also be a source of virus capable of reseeding peripheral systems. To examine this possibility, 200 μl of cell-free NCSU1 FIV or FIV-infected choroid plexus macrophages (ChP-Mac) was directly injected into the right lateral ventricle of the brain. Negative controls were sham inoculated with uninfected ChP-Mac or virus-free culture supernatant and positive controls were infected systemically by intraperitoneal (i.p.) injection. Intracerebroventricular (i.c.v.) inoculation with cell-free FIV resulted in high levels of plasma FIV RNA detected as early as 1 to 2 weeks post inoculation in all cats. In each case, the plasma viremia preceded the detection of CSF viral RNA. Compared to i.p. cats, i.c.v. cats had 32-fold higher CSF viral loads, 8-fold higher ratios of CSF to plasma viral load, and a 23-fold greater content of FIV proviral DNA in the brain. No FIV RNA was detected in plasma or CSF from the cats inoculated with FIV-infected ChP-Mac but an acute inflammatory response and a slight suppression of the CD4+:CD8+ ratio were observed. These results indicate that free FIV circulating in the CSF promotes infection of the CNS and provides a highly efficient pathway for the transfer of infectious virus to the periphery.}, number={4}, journal={JOURNAL OF NEUROVIROLOGY}, author={Liu, Pinghuang and Hudson, Lola C. and Tompkins, Mary B. and Vahlenkamp, Thomas W. and Colby, Brenda and Rundle, Cyndi and Meeker, Rick B.}, year={2006}, month={Aug}, pages={294–306} }
 @article{liu_hudson_tompkins_vahlenkamp_meeker_2006, title={Compartmentalization and evolution of feline immunodeficiency virus between the central nervous system and periphery following intracerebroventricular or systemic inoculation}, volume={12}, ISSN={["1355-0284"]}, DOI={10.1080/13550280600889575}, abstractNote={The emergence of distinct neuropathogenic strains resulting from the adaptation and the unique evolution of human immunodeficiency virus (HIV) in the brain may contribute to the development of HIV-induced neurological diseases. In this study, the authors tracked early changes in virus evolution and compartmentalization between peripheral tissues and the central nervous system (CNS) after intracerebroventricular (i.c.v.) or intraperitoneal (i.p.) inoculation of animals with cell-free feline immunodeficiency virus (FIV). Using the FIV-NCSU1 envelope V3–V4 heteroduplex tracking assay (HTA), the authors observed a rapid compartmentalization of envelope variants between the CNS and periphery. Animals receiving the i.c.v. inoculation showed two peaks of viral RNA in the cerebrospinal fluid (CSF) with very different HTA patterns. Compared to the initial viral peak in CSF, the second peak showed an increased compartmentalization from plasma, reduced viral diversity, and more divergence from the proviral DNA in peripheral blood mononuclear cells (PBMCs) and the choroid plexus. In contrast, changes in plasma over the same time period were small. Different animals harbored different FIV DNA genotypes with varied regional compartmentalization within the brain. These results demonstrated that the virus within the CNS experienced a relatively independent but variable evolution from the periphery. Initial penetration of virus into the CSF facilitated the development of brain-specific reservoirs and viral diversification within the CNS.}, number={4}, journal={JOURNAL OF NEUROVIROLOGY}, author={Liu, Pinghuang and Hudson, Lola C. and Tompkins, Mary B. and Vahlenkamp, Thomas W. and Meeker, Rick B.}, year={2006}, month={Aug}, pages={307–321} }