Format

Send to:

Choose Destination

See 1 citation found by title matching your search:

See comment in PubMed Commons below
Cell Host Microbe. 2011 Dec 15;10(6):563-76. doi: 10.1016/j.chom.2011.10.014.

Adeno-associated virus 2 infection requires endocytosis through the CLIC/GEEC pathway.

Author information

  • 1Cardiovascular Research Center, Mount Sinai School of Medicine, New York, NY 10029, USA.

Abstract

Adeno-associated viruses (AAVs) are nonpathogenic, nonenveloped, single-stranded DNA viruses in development as gene therapy vectors. AAV internalization was postulated to proceed via a dynamin-dependent endocytic mechanism. Revisiting this, we find that infectious endocytosis of the prototypical AAV, AAV2, is independent of clathrin, caveolin, and dynamin. AAV2 infection is sensitive to EIPA, a fluid-phase uptake inhibitor, but is unaffected by Rac1 mutants or other macropinocytosis inhibitors. In contrast, AAV2 infection requires actin cytoskeleton remodeling and membrane cholesterol and is sensitive to inhibition of Cdc42, Arf1, and GRAF1, factors known to be involved in the formation of clathrin-independent carriers (CLIC). AAV2 virions are internalized in the detergent-resistant GPI-anchored-protein-enriched endosomal compartment (GEEC) and translocated to the Golgi apparatus, similarly to the CLIC/GEEC marker cholera toxin B. Our results indicate that-unlike the viral entry mechanisms described so far-AAV2 uses the pleiomorphic CLIC/GEEC pathway as its major endocytic infection route.

Copyright © 2011 Elsevier Inc. All rights reserved.

PMID:
22177561
[PubMed - indexed for MEDLINE]
PMCID:
PMC3257174
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk