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- W2168227311 abstract "HIV-1 Gag assembles into virus particles predominantly at the plasma membrane (PM). Previously, we observed that phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P(2)] is essential for Gag binding to the plasma membrane and virus release in HeLa cells. In the current study, we found that PI(4,5)P(2) also facilitates Gag binding to the PM and efficient virus release in T cells. Notably, serial passage of HIV-1 in an A3.01 clone that expresses polyphosphoinositide 5-phosphatase IV (5ptaseIV), which depletes cellular PI(4,5)P(2), yielded an adapted mutant with a Leu-to-Arg change at matrix residue 74 (74LR). Virus replication in T cells expressing 5ptaseIV was accelerated by the 74LR mutation relative to replication of wild type HIV-1 (WT). This accelerated replication of the 74LR mutant was not due to improved virus release. In control T cells, the 74LR mutant releases virus less efficiently than does the WT, whereas in cells expressing 5ptaseIV, the WT and the 74LR mutant are similarly inefficient in virus release. Unexpectedly, we found that the 74LR mutation increased virus infectivity and compensated for the inefficient virus release. Altogether, these results indicate that PI(4,5)P(2) is essential for Gag-membrane binding, targeting of Gag to the PM, and efficient virus release in T cells, which in turn likely promotes efficient virus spread in T cell cultures. In T cells with low PI(4,5)P(2) levels, however, the reduced virus particle production can be compensated for by a mutation that enhances virus infectivity." @default.
- W2168227311 created "2016-06-24" @default.
- W2168227311 creator A5003159518 @default.
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- W2168227311 creator A5062424208 @default.
- W2168227311 date "2011-04-01" @default.
- W2168227311 modified "2023-09-24" @default.
- W2168227311 title "Assembly and Replication of HIV-1 in T Cells with Low Levels of Phosphatidylinositol-(4,5)-Bisphosphate" @default.
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- W2168227311 doi "https://doi.org/10.1128/jvi.02266-10" @default.
- W2168227311 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3067840" @default.
- W2168227311 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21270152" @default.
- W2168227311 hasPublicationYear "2011" @default.
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