Regulated expression of human immunodeficiency virus type 1 in human glial cells: induction of dormant virus.

Important note: Information in this article was accurate in 1993. The state of the art may have changed since the publication date.

Regulated expression of human immunodeficiency virus type 1 in human glial cells: induction of dormant virus.

Pathobiology. 1992;60(4):195-205. Unique Identifier : AIDSLINE MED/93000463
Shahabuddin M; Volsky B; Kim H; Sakai K; Volsky DJ; Molecular Virology Laboratory, St. Luke's/Roosevelt Hospital; Center and College of Physicians & Surgeons, Columbia University,; New York, N.Y. 10019.

Abstract: Human neural cells are susceptible to infection with human immunodeficiency virus type 1 (HIV-1) in vitro; however, virus replication in these cells is strongly restricted. To understand the mechanism of this restriction, we examined the regulation of HIV-1 expression in glial cell cultures expressing high levels of HIV-1 after transfection of infectious viral DNA and selection. In all cases, high HIV-1 expression declined to low basal levels within 4-8 weeks of cultivation. The decrease in HIV-1 protein production wa paralleled by the decline in the relative levels of the 9.2-, 4.3- and 1.8-kilobase HIV-1 transcripts, but not by significant loss of HIV-1 DNA. Analysis of one long-term cell culture revealed 5 full-length unrearranged HIV-1 DNA copies per cell, but no viral transcripts on Northern blots, and minimal production of infectious virus. HIV-1 replication in these cells was markedly augmented by treatment with sodium butyrate (Na But) and to a lesser extent by 5-azacytidine, dibutyryl AMP and human herpes virus type 6. The virus induced by Na But was infectious. Transient expression assays revealed that Na But was more effective than phorbol myristate acetate in increasing the HIV-1 promoter activity in glial cells. Thus, one phase where glial cells can limit HIV infection is the expression of viral RNA from stable HIV provirus. However, such provirus remains responsive to inductive signals and may be activated to produce infectious HIV.

Keywords: Cells, Cultured DNA, Viral/GENETICS Gene Expression Human HIV-1/DRUG EFFECTS/*GROWTH & DEVELOPMENT/GENETICS Neuroglia/*MICROBIOLOGY RNA, Viral/GENETICS Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. Time Factors Virus Replication/DRUG EFFECTS JOURNAL ARTICLE
930130
M9311115

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