Characterization of novel mutations in the HIV-1 Env glycoprotein that enhance cell-to-cell viral transfer

Tuesday, September 23, 2014 — Poster Session III
12:00 p.m. – 2:00 p.m.	FAES Academic Center	NCI	VIROL-9

Authors

• R Van Duyne
• L Kuo
• K Fujii
• E.O. Freed

Abstract

Infectious HIV-1 particle production is driven by the expression of the Gag polyprotein precursor that acts to recruit host cell factors to assist in viral budding. The p6 domain of HIV-1 Gag contains a YPXnL motif that interacts directly with the endosomal-associated protein Alix. Upon passaging in culture, replication-defective Alix-binding site mutants revert to viruses with near-wild-type replication kinetics. Sequencing of these viruses revealed novel mutations in the HIV-1 Env gene, Y61H, P81S, A556T, I744V, and R786K, which not only exhibit a full rescue of the original Gag mutants, but also exhibit replication kinetics faster than those of wild-type HIV-1 in Jurkat T-cells. To explain this phenomenon, we recently determined that these Env mutants exhibit no effect on the processing of Gag, the incorporation of Env, or virus release efficiency, some decrease fusogenicity and all decrease single-cycle infectivity. We concluded that these Env mutations have no effect on cell-free infectivity and instead propose that these mutations enhance cell-to-cell viral transmission. Cell-to-cell HIV-1 transmission occurs more efficiently and rapidly than infection by cell-free viruses, supporting the relevance of this mode of viral dissemination. Further characterization of these mutants will provide key insights into the role of Env in cell-cell virus transfer.

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