Rab7A is required for efficient production of infectious HIV-1.

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.

• Authors: Marina Caillet, Katy Janvier, Annegret Pelchen-Matthews, Delphine Delcroix-Genête, Grégory Camus, Mark Marsh, Clarisse Berlioz-Torrent
• Journal: PLoS pathogens (PLoS Pathog) Vol. 7 Issue 11 Pg. e1002347 (Nov 2011) ISSN: 1553-7374 [Electronic] United States
• PMID: 22072966 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD
• BST2 protein, human
• GPI-Linked Proteins
• Human Immunodeficiency Virus Proteins
• RNA, Small Interfering
• Viral Regulatory and Accessory Proteins
• env Gene Products, Human Immunodeficiency Virus
• rab7 GTP-Binding Proteins
• vpu protein, Human immunodeficiency virus 1
• rab GTP-Binding Proteins

Topics

• Antigens, CD (biosynthesis, metabolism)
• Cell Membrane (metabolism, virology)
• Endosomes (metabolism)
• GPI-Linked Proteins (biosynthesis, metabolism)
• HEK293 Cells
• HIV-1 (genetics, growth & development, metabolism)
• HeLa Cells
• Human Immunodeficiency Virus Proteins (metabolism)
• Humans
• Protein Transport
• RNA Interference
• RNA, Small Interfering
• Viral Regulatory and Accessory Proteins (metabolism)
• Virus Release
• env Gene Products, Human Immunodeficiency Virus (biosynthesis, metabolism)
• rab GTP-Binding Proteins (genetics, metabolism)
• rab7 GTP-Binding Proteins