Transcriptional Regulation of Latent Feline Immunodeficiency Virus in Peripheral CD4+ T-lymphocytes

Feline immunodeficiency virus (FIV), the lentivirus of domestic cats responsible for feline AIDS, establishes a latent infection<strong> </strong>in peripheral blood CD4+ T-cells approximately eight months after experimental inoculation. In this study, cats experimentally...

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Main Authors: Brian G. Murphy, Samantha J. McDonnel, Ellen E. Sparger, Paul A. Luciw
Format: Article
Language:English
Published: MDPI AG 2012-05-01
Series:Viruses
Subjects:
Online Access:http://www.mdpi.com/1999-4915/4/5/878
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author Brian G. Murphy
Samantha J. McDonnel
Ellen E. Sparger
Paul A. Luciw
author_facet Brian G. Murphy
Samantha J. McDonnel
Ellen E. Sparger
Paul A. Luciw
author_sort Brian G. Murphy
collection DOAJ
description Feline immunodeficiency virus (FIV), the lentivirus of domestic cats responsible for feline AIDS, establishes a latent infection<strong> </strong>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 10<sup>3</sup> 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 <em>in vitro</em> studies. Thus, the FIV/cat model may offer insights into <em>in vivo</em> mechanisms of HIV latency and provides a unique opportunity to test novel therapeutic interventions aimed at eradicating latent virus.
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spelling doaj.art-e064e4a2aa5146d7bd4539b60a8e6e392022-12-21T19:10:33ZengMDPI AGViruses1999-49152012-05-014587888810.3390/v4050878Transcriptional Regulation of Latent Feline Immunodeficiency Virus in Peripheral CD4+ T-lymphocytesBrian G. MurphySamantha J. McDonnelEllen E. SpargerPaul A. LuciwFeline immunodeficiency virus (FIV), the lentivirus of domestic cats responsible for feline AIDS, establishes a latent infection<strong> </strong>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 10<sup>3</sup> 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 <em>in vitro</em> studies. Thus, the FIV/cat model may offer insights into <em>in vivo</em> mechanisms of HIV latency and provides a unique opportunity to test novel therapeutic interventions aimed at eradicating latent virus.http://www.mdpi.com/1999-4915/4/5/878FIVlatencylentiviruschromatintranscriptionCD4 T-cells
spellingShingle Brian G. Murphy
Samantha J. McDonnel
Ellen E. Sparger
Paul A. Luciw
Transcriptional Regulation of Latent Feline Immunodeficiency Virus in Peripheral CD4+ T-lymphocytes
Viruses
FIV
latency
lentivirus
chromatin
transcription
CD4 T-cells
title Transcriptional Regulation of Latent Feline Immunodeficiency Virus in Peripheral CD4+ T-lymphocytes
title_full Transcriptional Regulation of Latent Feline Immunodeficiency Virus in Peripheral CD4+ T-lymphocytes
title_fullStr Transcriptional Regulation of Latent Feline Immunodeficiency Virus in Peripheral CD4+ T-lymphocytes
title_full_unstemmed Transcriptional Regulation of Latent Feline Immunodeficiency Virus in Peripheral CD4+ T-lymphocytes
title_short Transcriptional Regulation of Latent Feline Immunodeficiency Virus in Peripheral CD4+ T-lymphocytes
title_sort transcriptional regulation of latent feline immunodeficiency virus in peripheral cd4 t lymphocytes
topic FIV
latency
lentivirus
chromatin
transcription
CD4 T-cells
url http://www.mdpi.com/1999-4915/4/5/878
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