Endocytosis and Nuclear Trafficking of Adeno-Associated Virus Type 2 Are Controlled by Rac1 and Phosphatidylinositol-3 Kinase Activation

Salih Sanlioglu; Peter K Benson; Jusan Yang; E. Morrey Atkinson; Thomas Reynolds; John F Engelhardt

doi:10.1128/JVI.74.19.9184-9196.2000

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Endocytosis and Nuclear Trafficking of Adeno-Associated Virus Type 2 Are Controlled by Rac1 and Phosphatidylinositol-3 Kinase Activation

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Endocytosis and Nuclear Trafficking of Adeno-Associated Virus Type 2 Are Controlled by Rac1 and Phosphatidylinositol-3 Kinase Activation

Salih Sanlioglu, Peter K Benson, Jusan Yang, E. Morrey Atkinson, Thomas Reynolds and John F Engelhardt

Journal of virology, Vol.74(19), pp.9184-9196

10/2000

DOI: 10.1128/JVI.74.19.9184-9196.2000

PMCID: PMC102117

PMID: 10982365

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Abstract

Adeno-associated virus (AAV) is a single-stranded DNA parvovirus that causes no currently known pathology in humans. Despite the fact that this virus is of increasing interest to molecular medicine as a vector for gene delivery, relatively little is known about the cellular mechanisms controlling infection. In this study, we have examined endocytic and intracellular trafficking of AAV-2 using fluorescent (Cy3)-conjugated viral particles and molecular techniques. Our results demonstrate that internalization of heparan sulfate proteoglycan-bound AAV-2 requires αVβ5 integrin and activation of the small GTP-binding protein Rac1. Following endocytosis, activation of a phosphatidylinositol-3 (PI3) kinase pathway was necessary to initiate intracellular movement of AAV-2 to the nucleus via both microfilaments and microtubules. Inhibition of Rac1 using a dominant N17Rac1 mutant led to a decrease in AAV-2-mediated PI3 kinase activation, indicating that Rac1 may act proximal to PI3 kinase during AAV-2 infection. In summary, our results indicate that αVβ5 integrin-mediated endocytosis of AAV-2 occurs through a Rac1 and PI3 kinase activation cascade, which directs viral movement along the cytoskeletal network to the nucleus.

Virus-Cell Interactions

Details

Title: Subtitle: Endocytosis and Nuclear Trafficking of Adeno-Associated Virus Type 2 Are Controlled by Rac1 and Phosphatidylinositol-3 Kinase Activation
Creators: Salih Sanlioglu - Department of Anatomy and Cell Biology and Center for Gene Therapy
Peter K Benson - Department of Anatomy and Cell Biology and Center for Gene Therapy
Jusan Yang - Department of Anatomy and Cell Biology and Center for Gene Therapy
E. Morrey Atkinson - Department of Anatomy and Cell Biology and Center for Gene Therapy
Thomas Reynolds - Department of Anatomy and Cell Biology and Center for Gene Therapy
John F Engelhardt - Department of Anatomy and Cell Biology and Center for Gene Therapy
Resource Type: Journal article
Publication Details: Journal of virology, Vol.74(19), pp.9184-9196
DOI: 10.1128/JVI.74.19.9184-9196.2000
PMID: 10982365
PMCID: PMC102117
NLM abbreviation: J Virol
ISSN: 0022-538X
eISSN: 1098-5514
Publisher: American Society for Microbiology
Language: English
Date published: 10/2000
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Anatomy and Cell Biology; Radiation Oncology; Internal Medicine
Record Identifier: 9984025440202771

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