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Transcriptional Regulation of Latent Feline Immunodeficiency Virus in Peripheral CD4+ T-lymphocytes
Department of Pathology, Microbiology & Immunology, School of Veterinary Medicine, University of California, Davis, 4206 Vet Med 3A, Davis, CA 95616, USA
Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, 3115 Tupper Hall, Davis, CA 95616, USA
Department of Pathology and Laboratory Medicine, Center for Comparative Medicine, University of California, Davis, County Road 98 and Hutchison Drive, Davis, CA 95616, USA
* Author to whom correspondence should be addressed.
Received: 23 April 2012; in revised form: 12 May 2012 / Accepted: 15 May 2012 / Published: 23 May 2012
Abstract: Feline immunodeficiency virus (FIV), the lentivirus of domestic cats responsible for feline AIDS, establishes a latent infection in 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.
Keywords: FIV; latency; lentivirus; chromatin; transcription; CD4 T-cells
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McDonnel, S.J.; Sparger, E.E.; Luciw, P.A.; Murphy, B.G. Transcriptional Regulation of Latent Feline Immunodeficiency Virus in Peripheral CD4+ T-lymphocytes. Viruses 2012, 4, 878-888.
McDonnel SJ, Sparger EE, Luciw PA, Murphy BG. Transcriptional Regulation of Latent Feline Immunodeficiency Virus in Peripheral CD4+ T-lymphocytes. Viruses. 2012; 4(5):878-888.
McDonnel, Samantha J.; Sparger, Ellen E.; Luciw, Paul A.; Murphy, Brian G. 2012. "Transcriptional Regulation of Latent Feline Immunodeficiency Virus in Peripheral CD4+ T-lymphocytes." Viruses 4, no. 5: 878-888.