FIV establishes a latent infection in feline peripheral blood CD4+ T lymphocytes in vivo during the asymptomatic phase of infection

In an approximately 2 year-long experimental infection study, cats infected with a biological isolate of FIV clade C demonstrated undetectable plasma viral loads from 10 months post-infection onward. Viral DNA was detected in CD4+CD25+ and CD4+CD25- T cells isolated from infected cats whereas viral RNA was not detected at multiple time points during the early chronic phase of infection. Viral transcription could be reactivated in latently infected CD4+ T cells ex vivo as demonstrated by detectable FIV gag RNA and 2-long terminal repeat (LTR) circle junctions. Viral LTR and gag sequences amplified from peripheral blood mononuclear cells during early and chronic stages of infection demonstrated minimal to no viral sequence variation.Collectively, these findings are consistent with FIV latency in peripheral blood CD4+ T cells isolated from chronically infected cats. The ability to isolate latently FIV-infected CD4+ T lymphocytes from FIV-infected cats provides a platform for the study of in vivo mechanisms of lentiviral latency.Feline immunodeficiency virus (FIV) infection of cats is an important animal model of human immunodeficiency virus-1 (HIV-1) pathogenesis [1-3]. These two viruses are phylogenetically related [4], and both infect na？ve and activated CD4+ T cell subsets as well as monocytes in the susceptible host [2,5,6]. FIV-infected cats develop an acute infection syndrome followed by a prolonged asymptomatic period during which the CD4/CD8 T cell ratio is inverted [5,7]. The asymptomatic phase of infection is generally followed by a terminal immunodeficiency phase of disease termed feline acquired immunodeficiency syndrome (FAIDS), akin to AIDS [7-9].Latently infected resting CD4+ T cells are the best characterized reservoir for HIV-1 [10]. Such cells are viral DNA-positive and viral RNA-negative and are therefore effectively invisible to pharmacologic therapy and immunological surveillance. The maintenance of latent HIV infection in resting T cells of patien