The acquisition of host-derived major histocompatibility complex class II glycoproteins by human immunodeficiency virus type 1 accelerates the process of virus entry and infection in human T-lymphoid cells.
Infection by human immunodeficiency virus type 1 (HIV-1) results in a progressive depletion of CD4+ T lymphocytes, leading to fatal immunodeficiency. The mechanisms causing the marked loss of CD4+ T lymphocytes are incompletely understood. However, several lines of evidence indicate that direct cytopathology mediated by HIV-1 is a key element in such CD4+ T-cell depletion. In this study, we investigated whether the previously reported incorporation of host-derived major histocompatibility class II glycoproteins (MHC-II) on HIV-1 can alter its replicative capacity. To achieve this goal, virus stocks were produced in parental MHC-II-expressing RAJI cells and in MHC-II-negative RAJI mutants (RM3), both of which have been stably transfected with human CD4 cDNA to allow productive infection with HIV-1. An enhancement of the rate/efficiency of virus entry was seen after infection with normalized amounts of virions carrying host-derived MHC-II on their surface as compared with inoculation with virions devoid of cellular MHC-II. Data from time-course and infectivity experiments showed that the kinetics of infection were more rapid for virions bearing host-derived MHC-II glycoproteins than for MHC-II-free HIV-1 particles. These results suggest that virally embedded cellular MHC-II glycoproteins are functional and can have a positive effect on early events in the virus replicative cycle. Therefore, we show that the acquisition of cellular MHC-II glycoproteins by HIV-1 can modify its biologic properties and might, consequently, influence the pathogenesis of this retroviral disease.
Cantin
R
R
Centre Hospitalier Universitaire de Québec, Pavillon CHUL, and the Département de Microbiologie, Faculté de Médecine, Université Laval, Ste-Foy, Canada.
Fortin
J F
JF
Lamontagne
G
G
Tremblay
M
M
D001402:B-Lymphocytes / Q000821:virology; D002051:Burkitt Lymphoma / Q000276:immunology / Q000473:pathology; D015704:CD4 Antigens / Q000235:genetics / Q000276:immunology; D004198:Disease Susceptibility; D005802:Genes, MHC Class II; D015497:HIV-1 / Q000737:chemistry / Q000276:immunology* / Q000502:physiology; D006681:HLA-D Antigens / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008562:Membrane Glycoproteins / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000821:virology*; D014162:Transfection; D014407:Tumor Cells, Cultured; D014771:Virion / Q000737:chemistry / Q000276:immunology*; D014779:Virus Replication
D015704:CD4 Antigens; D006681:HLA-D Antigens; D008562:Membrane Glycoproteins; D011993:Recombinant Fusion Proteins