Abstract
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.
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The present address of Thomas W. Vahlenkamp is Friedrich-Loeffler-Institute, Federal Research Institute for Animal Health, Greifswald-Insel Riems, Germany.
This study was supported by National Institutes of Health grant MH63646.