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PMID: 9120023 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Preferential replication of HIV-1 in the CD45RO memory cell subset of primary CD4 lymphocytes in vitro.

The Journal of clinical investigation ·Vol. 99 ·No. 7 ·1997-04-01 ·Pages 1774-85

Spina CA, Prince HE, Richman DD

Abstract

The ability of HIV-1 to establish an infection and replicate to high copy number in CD4 lymphocytes is dependent on both the activation state of the cell and virus-encoded regulatory proteins that modulate viral gene expression. To study these required virus-cell interactions, we have used an in vitro cell model of acute HIV infection of quiescent, primary CD4 lymphocytes and subsequent induction of T cell activation and virus replication by lectin or CD3 receptor cross-linking. Experiments were done to determine if the capacity of HIV to establish infection and complete replication was impacted by the maturational state of the CD4 cell target or the specific signal induction pathway engaged during activation. Primary CD4 cells were FACS-sorted into the major phenotypic subsets representative of memory (CD45RO) and naive (CD45RA) cells. Levels of virus replication were compared between infection with wild-type NL4-3 virus and an isogenic mutant containing a deletion in nef regulatory gene. PHA mitogen stimulation was compared with anti-CD3, with and without anti-CD28 costimulation, for induction of cell proliferation and virus replication. In both infected and uninfected cells, the RA cell subset exhibited significantly greater response to CD3/CD28 stimulation than did the RO cell subset. In contrast, the majority of virus replication occurred consistently in the RO cell subset. Deletion of HIV nef function caused a severe reduction in viral replication, especially in the RA naive cell subset after CD3 induction. PCR analysis of viral DNA formation, during infection of quiescent cells, demonstrated that the observed differences in HIV replication capacity between RO and RA cell subsets were not due to inherent differences in cell susceptibility to infection. Our results indicate that HIV replication is enhanced selectively in CD45RO memory phenotype cells through the probable contribution of specialized cellular factors which are produced during CD3-initiated signal transduction.

MeSH Terms
CD4-Positive T-Lymphocytes/immunology,virology Cells, Cultured HIV-1/physiology Humans Immunologic Memory Leukocyte Common Antigens/analysis Lymphocyte Activation Virus Replication
Chemicals
Leukocyte Common Antigens
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Spina C A
The Veterans Affairs Medical Center, San Diego, California 92161, USA. [email protected]
Prince H E
Richman D D
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI119342
Email
[email protected]
Published
1997-04-01
Pages
1774-85
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC507999
Subset
IM
Grants
NIAID NIH HHS · AI 27670 · United States
NIAID NIH HHS · AI 29164 · United States
NIAID NIH HHS · AI 38858 · United States
External Links
PubMed source DOI: 10.1172/JCI119342 PMC Full Text View journal details
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