Affiliation:
1. AIDS Vaccine Program1 and
2. Intramural Research Support Program,2SAIC-Frederick, National Cancer Institute at Frederick, Frederick, Maryland 21702-1201
Abstract
ABSTRACT
Human immunodeficiency virus (HIV) infection results in a functional impairment of CD4
+
T cells long before a quantitative decline in circulating CD4
+
T cells is evident. The mechanism(s) responsible for this functional unresponsiveness and eventual depletion of CD4
+
T cells remains unclear. Both direct effects of cytopathic infection of CD4
+
cells and indirect effects in which uninfected “bystander” cells are functionally compromised or killed have been implicated as contributing to the immunopathogenesis of HIV infection. Because T-cell receptor engagement of major histocompatibility complex (MHC) molecules in the absence of costimulation mediated via CD28 binding to CD80 (B7-1) or CD86 (B7-2) can lead to anergy or apoptosis, we determined whether HIV type 1 (HIV-1) virions incorporated MHC class I (MHC-I), MHC-II, CD80, or CD86. Microvesicles produced from matched uninfected cells were also evaluated. HIV infection increased MHC-II expression on T- and B-cell lines, macrophages, and peripheral blood mononclear cells (PBMC) but did not significantly alter the expression of CD80 or CD86. HIV virions derived from all MHC-II-positive cell types incorporated high levels of MHC-II, and both virions and microvesicles preferentially incorporated CD86 compared to CD80. CD45, expressed at high levels on cells, was identified as a protein present at high levels on microvesicles but was not detected on HIV-1 virions. Virion-associated, host cell-derived molecules impacted the ability of noninfectious HIV virions to trigger death in freshly isolated PBMC. These results demonstrate the preferential incorporation or exclusion of host cell proteins by budding HIV-1 virions and suggest that host cell proteins present on HIV-1 virions may contribute to the overall pathogenesis of HIV-1 infection.
Publisher
American Society for Microbiology
Subject
Virology,Insect Science,Immunology,Microbiology
Reference49 articles.
1. Chemical inactivation of retroviral infectivity by targeting nucleocapsid protein zinc fingers: a candidate SIV vaccine;Arthur L. O.;AIDS Res. Hum. Retrovir.,1998
2. Cellular proteins bound to immunodeficiency viruses: implications for pathogenesis and vaccines;Arthur L. O.;Science,1992
3. Barclay
N. A.
The leucocyte antigen facts book
2nd ed.
1997
Academic Press
London England
4. Host cell-dependent alterations in envelope components of human immunodeficiency virus type 1 virions
5. Microvesicles are a source of contaminating cellular proteins found in purified HIV-1 preparations;Bess J. W.;Virology,1997
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