Despite highly effective anti-retroviral therapy, HIV is thought to persist in patients within long-lived cellular reservoirs in the form of a transcriptionally inactive (latent) integrated provirus. Lentiviral latency has therefore come to the forefront of the discussion on the possibility of a cure for HIV infection in humans. Animal models of lentiviral latency provide an essential tool to study mechanisms of latency and therapeutic manipulation. Of the three animal models that have been described, the feline immunodeficiency virus (FIV)-infected cat is the most recent and least characterized. However, several aspects of this model make it attractive for latency research, and it may be complementary to other model systems. This article reviews what is known about FIV latency and chronic FIV infection and how it compares with that of other lentiviruses. It thereby offers a framework for the usefulness of this model in future research aimed at lentiviral eradication.
Feline immunodeficiency virus (FIV), the lentivirus of domestic cats responsible for feline AIDS, establishes a latent infectionin peripheral blood CD4+ T-cells approximately eight months after experimental inoculation. In this study, cats experimentally infected with the FIV-C strain in the asymptomatic phase demonstrated an estimated viral load of 1 infected cell per approximately 103 CD4+ T-cells, with about 1 copy of viral DNA per cell. Approximately 1 in 10 proviral copies was capable of transcription in the asymptomatic phase. The latent FIV proviral promoter was associated with deacetylated, methylated histones, which is consistent with a condensed chromatin structure. In contrast, the transcriptionally active FIV promoter was associated with histone acetylation and demethylation. In addition, RNA polymerase II appeared to be paused on the latent viral promoter, and short promoter-proximal transcripts were detected. Our findings for the FIV promoter in infected cats are similar to results obtained in studies of human immunodeficiency virus (HIV)-1 latent proviruses in cell culture in vitro studies. Thus, the FIV/cat model may offer insights into in vivo mechanisms of HIV latency and provides a unique opportunity to test novel therapeutic interventions aimed at eradicating latent virus.