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Liposomes modulate human immunodeficiency virus infectivity
K Konopka1, B R Davis, C E Larsen
1Cancer Research Institute, University of California, San Francisco 94143-0128.
Insights
Liposome fusion with human immunodeficiency virus type 1 (HIV-1) significantly alters viral infectivity. Certain liposomes enhance HIV-1 production and cell entry, while others inhibit it, impacting HIV-1
Area of Science:
- Virology
- Biotechnology
- Cell Biology
Background:
- Human immunodeficiency virus type 1 (HIV-1) infects CD4+ cells.
- Liposomes are lipid vesicles used in drug delivery and research.
- Understanding HIV-1-liposome interactions is crucial for therapeutic strategies.
Purpose of the Study:
- To investigate how liposome fusion affects HIV-1 infectivity.
- To determine the impact of different liposome compositions on HIV-1 infection.
- To explore liposome-mediated modulation of HIV-1 entry into target cells.
Main Methods:
- Fusion assays using fluorescence dequenching to assess HIV-1 and liposome interaction.
- Measuring HIV-1 production via p24 gag antigen quantification.
- Infectivity assays using CD4+ (A3.01, H9) and CD4- (K562) cell lines.
Main Results:
- HIV-1 fused with cardiolipin (CL) and N-[2,3-(dioleyloxy) propyl]-N,N,N-trimethyl ammonium chloride (DOTMA) liposomes, but not dioleoylphosphatidylcholine (DOPC) liposomes.
- DOTMA liposomes enhanced HIV-1 production and infectivity in CD4+ cells by up to 90-fold.
- CL liposomes inhibited HIV-1 infection in a concentration-dependent manner.
- DOPC liposomes had no significant effect on HIV-1 infectivity.
Conclusions:
- Liposome fusion with HIV-1 can significantly alter its infectivity.
- Specific liposome compositions, like DOTMA, can enhance HIV-1 infection.
- Other liposomes, like CL, can inhibit HIV-1 infection.
- These findings highlight the potential for liposomes to modulate HIV-1-host cell interactions.
Abstract:
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.