Herpesvirus Trans-Activation of Human Immunodeficiency Virus Type-1
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.
KeywordsHuman Immunodeficiency Virus Herpes Simplex Virus Type Permanent Cell Line IE175 Protein Specific Recognition Site
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- Campbell MEM, Palfreyman JW, Preston C (1984) Identification of herpes simplex virus DNA sequences which encode a trans-acting polypeptide responsible for stimulation of immediate early transcription. J MolGoogle Scholar
- Doerfler W (1983) DNA methylation and gene activity. Ann Rev BiochemGoogle Scholar
- Jones PA (1985) Altering gene expression with 5-azacytidine. Cell 40:485Keshet I, Hurwitz-Lieman J, Cedar H (1986) DNA methylation affects the formation of active chromatin. Cell 44: 535–543.Google Scholar
- Kirchner H (1982) Immunobiology of infections with herpes simplex virus. In: Melnick JL (ed), Monogram Virology Vol 13, pp 1–104.Google Scholar
- Mosca JD, Bednarik DP, Raj NBK, Rosen CA, Sodroski JG, Haseltine WA, Hayward GS, Pitha PM (1987b) Activation of human immunodeficiency virus by herpes virus infection: Identification of a region within the long terminal repeat that responds to a transacting factor encoded by herpes simplex virus 1. Proc Natl Acad Sci USA 84: 7408–7412.PubMedCrossRefGoogle Scholar
- O’Hare P, Hayward GS (1984) Expression of recombinant genes containing herpes simplex virus delayed-early and immediate-early regulatory regions and transactivation by herpesvirus infection. J Virol 52: 522531.Google Scholar
- Quinn TC, Piot P, McCormick JB, Feinsod FM, Taelman H, Kapita B, Stevens W, Fauci AS (1987) Serologic and immunologic studies in patients with AIDS in North American and African. The potential role of infectious agents as cofactors in human immunodeficiency virus infection. JAMAGoogle Scholar
- Rosen CA, Sodroski JB, Haseltine WA (1985) The location of cis-acting regulatory sequences in the human T-cell lymphotropic virus type III ( HTLV-III/LAV) long terminal repeat. Cell 41: 813–823.Google Scholar