Elsevier

Virology

Volume 294, Issue 2, 15 March 2002, Pages 246-255
Virology

Regular Article
Interaction between Nef and Phosphatidylinositol-3-Kinase Leads to Activation of p21-Activated Kinase and Increased Production of HIV

https://doi.org/10.1006/viro.2002.1365Get rights and content
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Abstract

The negative factor (Nef) is one of six accessory proteins from primate lentiviruses (HIV-1, HIV-2, and SIV). It leads to high levels of viremia and the progression to AIDS in monkeys and humans. In this study, we demonstrated that Nef from HIV-1 binds to the regulatory subunit (p85) of phosphatidylinositol-3-kinase (PI3K). This interaction depended on the C-terminus of p85 and Nef. Moreover, PI3K was required to activate the Nef-associated p21-activated kinase (PAK). Finally, inhibition of PI3K blocked the activation of PAK and decreased the production of viral particles to levels observed with the Nef-deleted provirus. We conclude that Nef assembles a multiprotein signaling complex which is required for the optimal replication of HIV-1.

Keywords

HIV
SIV
Nef
accessory proteins
signal transduction
Vav
PI3K
Rac
Cdc42
PAK

Cited by (0)

1

Present address: Department of Otorhinolaryngology, Head and Neck Surgery, Philipps University Marburg, Deutschhausstrasse 3, D-35037 Marburg, Germany.

2

To whom correspondence and reprint requests should be addressed at Room N226, UCSF Cancer Center, Mt. Zion Research Building, 2340 Sutter Street, San Francisco, CA 94115. Fax: (415) 502-1901. E-mail: [email protected].