Liposomes modulate human immunodeficiency virus infectivity.
We have investigated the effects of the fusion of liposomes with human immunodeficiency virus type 1 (HIV-1LVA) on the ability of the virus to infect CD4+ and CD4- cells. Fluorescence dequenching measurements indicated that HIV-1 fuses with liposomes composed of either cardiolipin (CL) or N-[2,3-(dioleyloxy) propyl]-N,N,N-trimethyl ammonium chloride (DOTMA) but not appreciably with dioleoylphosphatidylcholine (DOPC) liposomes. Pre-incubation of HIV-1 with DOTMA liposomes enhanced virus production (measured by p24 gag antigen production in the culture medium and in situ) in CD4+ A3.01 and H9 cells in a concentration-dependent manner, but did not mediate the infection of the CD4- cell line, K562. Preincubation of HIV-1 with between 10 and 30 microM-DOTMA liposomes, and subsequent incubation with A3.01 cells, resulted in the production of about 30-fold greater levels of virus than controls. The presence of DOTMA liposomes during the incubation of A3.01 cells with HIV-1 enhanced the infectivity of the virus up to 90-fold compared to controls. Conversely, preincubation of HIV-1 with CL liposomes inhibited infection of A3.01 cells, dependent on the concentration of liposomes; DOPC liposomes did not alter the infectivity of the virus under any of the incubation conditions. Our results thus indicate that fusion of HIV-1 with liposomes alters the ability of the virus to infect its target cells.
Konopka
K
K
Cancer Research Institute, University of California, San Francisco 94143-0128.
Davis
B R
BR
Larsen
C E
CE
Alford
D R
DR
Debs
R J
RJ
Düzgüneş
N
N
D015704:CD4 Antigens / Q000276:immunology*; D002308:Cardiolipins / Q000494:pharmacology; D002460:Cell Line; D004279:DNA, Viral / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D008081:Liposomes; D008561:Membrane Fusion; D010713:Phosphatidylcholines / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects*
D015704:CD4 Antigens; D002308:Cardiolipins; D004279:DNA, Viral; D008081:Liposomes; D010713:Phosphatidylcholines; D000644:Quaternary Ammonium Compounds; C054005:N-(1-(2,3-dioleyloxy)propyl)-N,N,N-trimethylammonium; C017251:1,2-oleoylphosphatidylcholine