THE PRESENCE OF HOST-DERIVED HLA-DR1 ON HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INCREASES VIRAL INFECTIVITY

Human immunodeficiency virus type 1 (HIV-1) incorporates several host cell components when budding out of the infected cell. One of the most abundant host-derived molecules acquired by HIV-1 is the HLA-DR deter minant of the major histocompatibility complex class II (MHC-II) molec ules. The fact that CD4 is the natural ligand of MHC-II prompted us to determine if such virally embedded cellular components can affect the biology of the virus. Herein, we report for the first time that the i ncorporation of cellular HLA-DR1 within HIV-1 enhances its infectivity . This observation was made possible with virions bearing or not beari ng on their surfaces host-derived HLA-DR1 glycoproteins. Such virus st ocks were prepared by a transient-expression system based on transfect ion of 293T cells with a recombinant luciferase-encoding HIV-1 molecul ar clone along with plasmids encoding the alpha and beta chains of HLA -DR1. Cell-free virions recovered from transfected cells were shown to have efficiently incorporated host-derived HLA-DR1 glycoproteins. Inf ectivity was increased by a factor of 1.6 to 2.3 for virions bearing o n their surfaces host-derived HLA-DRL. The observed enhancement of HIV -I infectivity was independent of the virus stocks used and was seen I n several T-lymphoid cell lines, in a premonocytoid cell line, and in primary peripheral blood mononuclear cells. Finally we determined that the presence of virion-bound cellular HLA-DR1 is associated with fast er kinetics of virus infection. Taken together, these results suggest that HLA-DR-1-bearing HIV-1 particles had a greater infectivity per pi cogram of viral p24 protein than HLA-DR1-free virions.