Enhancement of human immunodeficiency virus type 1 infection by cationic liposomes: the role of CD4, serum and liposome-cell interactions.
We have reported previously the enhancement of the infectivity of human immunodeficiency virus type 1 (HIV-1) by liposomes composed of the cationic lipid N-[2,3-(dioleyloxy) propyl]-N,N,N-trimethylammonium chloride (DOTMA). To determine the mechanism by which this process occurs, we have investigated the role of CD4, serum concentration and liposome-cell interactions in the DOTMA-mediated stimulation of HIV-1 infection of A3.01 cells. Serum alone significantly inhibited the binding and infectivity of HIV-1, but DOTMA-mediated enhancement of infectivity was more pronounced in the presence of serum than in its absence. HIV-1 binding to cells was increased in the presence of DOTMA liposomes, DEAE-dextran and polybrene, all of which also enhanced infectivity to a similar extent at comparable concentrations. Fluorescence dequenching measurements indicated that DOTMA liposomes fused with HIV-1, but not with cell membranes, in the presence of serum. The enhancing effect of DOTMA liposomes on HIV-1 infectivity was CD4-dependent, and appeared to involve virus-liposome fusion and liposome binding to the cell surface. DOTMA liposomes did not mediate infection of the CD4-K562 and Raji cell lines.
Konopka
K
K
Cancer Research Institute, University of California, San Francisco 94143-0128.
Stamatatos
L
L
Larsen
C E
CE
Davis
B R
BR
Düzgüneş
N
N
D000911:Antibodies, Monoclonal; D001769:Blood; D015704:CD4 Antigens / Q000502:physiology*; D002460:Cell Line; D003637:DEAE-Dextran / Q000494:pharmacology; D015726:Giant Cells / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects / Q000472:pathogenicity*; D006583:Hexadimethrine Bromide / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008081:Liposomes; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014779:Virus Replication
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D008081:Liposomes; D000644:Quaternary Ammonium Compounds; C054005:N-(1-(2,3-dioleyloxy)propyl)-N,N,N-trimethylammonium; D006583:Hexadimethrine Bromide; D003637:DEAE-Dextran