Plos Pathogens paper for the Marsh Group

Rab7A is required for efficient production of infectious HIV-1

Authors

Caillet, M., Javier, K., Pelchen-Matthews, A., Delcroix-Genete, D., Camus, G., Marsh, M., and Berlioz-Torrent, C.

Abstract

Retroviruses
take advantage of cellular trafficking machineries to assemble and
release new infectious particles. Rab proteins regulate specific steps
in intracellular membrane trafficking by recruiting tethering, docking
and fusion factors, as well as the actin- and microtubule-based motor
proteins that facilitate vesicle traffic. Using virological tests and
RNA interference targeting Rab proteins, we demonstrate that the late
endosome-associated Rab7A is required for HIV-1 propagation. Analysis of
the late steps of the HIV infection cycle shows that Rab7A regulates
Env processing, the incorporation of mature Env glycoproteins into viral
particles and HIV-1 infectivity. We also show that siRNA-mediated Rab7A
depletion induces a BST2/Tetherin phenotype on HIV-1 release.
BST2/Tetherin is a restriction factor that impedes HIV-1 release by
tethering mature virus particles to the plasma membrane. Our results
suggest that Rab7A contributes to the mechanism by which Vpu counteracts
the restriction factor BST2/Tetherin and rescues HIV-1 release.
Altogether, our results highlight new roles for a major regulator of the
late endocytic pathway, Rab7A, in the late stages of the HIV-1
replication cycle.