Differential incorporation of CD45, CD80 (B7-1), CD86 (B7-2), and major histocompatibility complex class I and II molecules into human immunodeficiency virus type 1 virions and microvesicles: implications for viral pathogenesis and immune regulation

Human immunodeficiency virus (HIV) infection results in a functional impair ment of CD4(+) T cells long before a quantitative decline in circulating CD 4(+) T cells is evident. The mechanism(s) responsible for this functional u nresponsiveness and eventual depletion of CD4(+) T cells remains unclear. B oth direct effects of cytopathic infection of CD4' cells and indirect effec ts in which uninfected "bystander" cells are functionally compromised or ki lled have been implicated as contributing to the immunopathogenesis of HIV infection, Because T-cell receptor engagement of major histocompatibility c omplex (MHC) molecules in the absence of costimulation mediated via CD28 bi nding to CD80 (B7-1) or CD86 (B7-2) can Lead to anergy or apoptosis, we det ermined whether HIV type 1 (HIV-1) virions incorporated MHC class I (MHC-I) , MHC-II, CD80, or CD86. Microvesicles produced from matched uninfected cel ls were also evaluated. HIV infection increased MHC-II expression on T- and B-cell lines, macrophages, and peripheral blood mononclear cells (PBMC) bu t did not significantly alter the expression of CD80 or CD86. HIV virions d erived from all MHC-II-positive cell types incorporated high levels of MHC- II, and both virions and microvesicles preferentially incorporated CD86 com pared 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 HI V-1 virions. Virion-associated, host cell-derived molecules impacted the ab ility of noninfectious HIV virions to trigger death in freshly isolated PBM C, These results demonstrate the preferential incorporation or exclusion of host cell proteins by budding HIV-1 virions and suggest that host cell pro teins present on HIV-1 virions may contribute to the overall pathogenesis o f HIV-I infection.