How ABCB4 Affects HIV Infectivity
Author Information
Author(s): Niek P van Til, Kirstin M Heutinck, Roos van der Rijt, Coen C Paulusma, Michel van Wijland, David M Markusic, Ronald PJ Oude Elferink, Jurgen Seppen
Primary Institution: AMC Liver Center, Amsterdam, the Netherlands
Hypothesis
The low viral titers were caused by ABCB4 mediated changes in the phospholipid composition of the lentiviral membrane.
Conclusion
Increasing the phosphatidylcholine content of HIV particles reduces their infectivity.
Supporting Evidence
- Virus generated in the presence of ABCB4 was enriched in phosphatidylcholine and cholesterol but contained less sphingomyelin.
- Viral titers were reduced 5.9 fold when ABCB4 was expressed.
- The presence of an inactive ABCB4 mutant did not affect viral titers.
- The ABC transport inhibitor verapamil abolished the effect of ABCB4 expression on viral titers.
Takeaway
This study found that changing the fats in the HIV virus can make it less able to infect cells.
Methodology
The study involved expressing wild type and mutant ABCB4 during viral vector production and measuring the effects on viral titers and lipid composition.
Limitations
The study was performed with VSVg pseudotyped HIV particles, which may not fully represent wild type HIV.
Statistical Information
P-Value
p<0.01
Statistical Significance
p<0.01
Digital Object Identifier (DOI)
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