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Herpesvirus Trans-Activation of Human Immunodeficiency Virus Type-1

  • Joseph D. Mosca
Conference paper

Abstract

In humans, HIV-1 infection is characterized by a period of latency followed by progression to acquired immunodeficiency syndrome (AIDS) and AIDS-related complex in some cases (Blattner et al. 1985). Factors that influence HIV-1 latency are poorly understood. Several models have been proposed that might explain. how HIV-1, when persisting in the latent form, can be induced by physiochemical stimuli and expressed as infectious virus particles (Folks et al. 1986). These models include transcriptional repression of integrated proviral DNA by DNA-binding proteins, chromatin conformation, and DNA hypermethylation. To understand these processes, permanent cell lines were constructed that contained as a reporter gene the bacterial chloramphenicol acetyltransferase (CAT) gene coding region fused to the HIV-1-LTR (pU3R-III-CAT) or human T leukemia virus (HTLV) type I (HTLV-I)-LTR (pU3R-I-CAT) promoter sequences. In these permanent cell lines HIV-1-LTR but not HTLV-I-LTR expression was suppressed when integrated into the host chromatin (Mosca et al. 1987a). We have provided evidence that the suppression of HIV-1-LTR expression is accompanied by methylation of LTR sequences (Bednarik et al. 1987). Using these permanent cell lines as a model system that appears to mimic the latent integrated HIV-1 provirus, we showed that reactivation of the reporter CAT gene initiated from the HIV-1-LTR can be induced by either treatment with a protein synthesis inhibitor (cycloheximide) or infection with herpesviruses (Mosca et al. 1987a). For herpes simplex virus I (HSV-1), we have identified the 5’ upstream sequence within the HIV-1-LTR that appears to contain a specific recognition site necessary for the activation by HSV-1 and by the HSV-1 encoded IE110 (ICPO) regulatory protein (Mosca et al. 1987b). However, for reactivation of the HIV-1-LTR by cytomegalovirus (CMV), no specific recognition sequence within the HIV-1-LTR could be found, indicating that different molecular mechanisms exist for HIV-1-LTR activation by HSV-1 and CMV.

Keywords

Human Immunodeficiency Virus Herpes Simplex Virus Type Permanent Cell Line IE175 Protein Specific Recognition Site 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1989

Authors and Affiliations

  • Joseph D. Mosca
    • 1
    • 2
  1. 1.Henry M. Jackson FoundationRockvilleUSA
  2. 2.Department of Immunology and Infectious DiseasesThe Johns Hopkins University School of Public HealthBaltimoreUSA

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