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 determinant of the major histocompatibility complex class II (MHC-II) molecules. 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 incorporation of cellular HLA-DR1 within HIV-1 enhances its infectivity. This observation was made possible with virions bearing or not bearing on their surfaces host-derived HLA-DR1 glycoproteins. Such virus stocks were prepared by a transient-expression system based on transfection of 293T cells with a recombinant luciferase-encoding HIV-1 molecular 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. Infectivity was increased by a factor of 1.6 to 2.3 for virions bearing on their surfaces host-derived HLA-DR1. The observed enhancement of HIV-1 infectivity was independent of the virus stocks used and was seen in 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 faster kinetics of virus infection. Taken together, these results suggest that HLA-DR-1-bearing HIV-1 particles had a greater infectivity per picogram of viral p24 protein than HLA-DR1-free virions.
Cantin
R
R
Département de Microbiologie, Faculté de Médecine, Université Laval, Québec, Canada.
Fortin
J F
JF
Lamontagne
G
G
Tremblay
M
M
D002460:Cell Line; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D016655:HIV Core Protein p24 / Q000032:analysis; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D015798:HLA-DR1 Antigen / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000821:virology; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014771:Virion
D016655:HIV Core Protein p24; D015798:HLA-DR1 Antigen; D008156:Luciferases