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ADP-ribosylation factor 1 in HIV-1 assembly and release

Tuesday, October 09, 2012 — Poster Session I

1:00 p.m. – 3:00 p.m

Natcher Conference Center, Building 45




  • PR Tedbury
  • N Kuruppu
  • EO Freed


HIV-1 budding is driven by the Gag polyprotein precursor and requires homotypic interactions between Gag molecules and interactions between Gag and host-cell components. It is known that Gag localizes to membranes enriched with phosphatidylinositol-4,5-bisphosphate (PIP2). However, the precise mechanism of Gag trafficking to these sites remains obscure. Work in this lab has previously described ADP ribosylation factors (Arfs) as host factors affecting the release of HIV-1. A panel of Arf mutants was generated to determine the specificity of the requirement of HIV for Arf proteins in over-expression experiments. Only Arf1 DN inhibited virus release without affecting cell viability. Metabolic labelling of Gag showed perturbation of Gag processing and potentially membrane binding, however there is no apparent effect on PIP2. Chimera-based experiments exploiting the near-identity between Arf1 and Arf3 suggested Arf1-guanidine exchange factors (GEFs) interactions as critical to the inhibition of HIV release; these have been further examined by silencing of known Arf1 GEFs. Direct interactions between Gag and Arf1 and Arf3 are also being investigated both via incorporation into particles and two-hybrid experiments. These approaches are revealing novel insights into the interactions between HIV-1 and the host cell, Gag trafficking and the distinct cellular functions of Arf proteins.

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