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PMID: 8892923 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

A mechanism of restricted human immunodeficiency virus type 1 expression in human glial cells.

Journal of virology ·Vol. 70 ·No. 11 ·1996-11-00 ·Pages 7992-8002

Shahabuddin M, Bentsman G, Volsky B, Rodriguez I, Volsky DJ

Abstract

We characterized in detail the life cycle of human immunodeficiency virus type 1 (HIV-1) in human glioma H4/CD4 cells which stably express transfected CD4 DNA (B. Volsky, K. Sakai, M. Reddy, and D. J. Volsky, Virology 186:303-308, 1992). Infection of cloned H4/CD4 cells with the N1T strain of cell-free HIV-1 (HIV-1/N1T) was rapid and highly productive as measured by the initial expression of viral DNA, RNA, and protein, but all viral products declined to low levels by 14 days after infection. Chronically infected, virus-producing H4/CD4 cells could be obtained by cell cloning, indicating that HIV-1 DNA can integrate and remain expressed in these cells. The HIV-1 produced in H4/CD4 cells was noninfectious to glial cells, but it could be transmitted with low efficiency to CEM cells. Examination of viral protein composition by immunoprecipitation with AIDS serum or anti-gp120 antibody revealed that HIV-1/N1T-infected H4/CD4 cells produced all major viral proteins including gp160, but not gp120. Deglycosylation experiments with three different glycosidases determined that the absence of gp120 was not due to aberrant glycosylation of gp160, indicating a defect in gp160 proteolytic processing. Similar results were obtained in acutely and chronically infected H4/CD4 cells. To determine the generality of this HIV-1 replication phenotype in H4/CD4 cells, nine different viral clones were tested for replication in H4/CD4 cells by transfection. Eight were transiently productive like N1T, but one clone, NL4-3, established a long-lived productive infection in H4/CD4 cells, produced infectious progeny virus, and produced both gp160 and gp120. We conclude that for most HIV-1 strains tested, HIV-1 infection of H4/CD4 is restricted to a single cycle because of the defective processing of gp160, resulting in the absence of gp120 on progeny virus.

MeSH Terms
Binding Sites CD4 Antigens/genetics,metabolism Cell Line Cell Line, Transformed Cell Survival DNA, Viral/metabolism HIV Core Protein p24/metabolism HIV Envelope Protein gp120/metabolism HIV Envelope Protein gp160/metabolism HIV Envelope Protein gp41/metabolism HIV-1/genetics,metabolism,physiology Humans Neuroglia/cytology,metabolism,virology RNA, Viral/metabolism Tumor Cells, Cultured Virus Replication
Chemicals
CD4 Antigens DNA, Viral HIV Core Protein p24 HIV Envelope Protein gp120 HIV Envelope Protein gp160 HIV Envelope Protein gp41 RNA, Viral
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Shahabuddin M
Molecular Virology Laboratory, St. Luke's-Roosevelt Hospital Center, New York, New York 10019, USA.
Bentsman G
Volsky B
Rodriguez I
Volsky D J
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.70.11.7992-8002.1996
Published
1996-11-00
Pages
7992-8002
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC190872
Subset
IM
Grants
NINDS NIH HHS · P01 NS031492 · United States
NINDS NIH HHS · NS PO1-31492 · United States
External Links
PubMed source DOI: 10.1128/JVI.70.11.7992-8002.1996 PMC Full Text View journal details
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