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J. Biol. Chem., Vol. 280, Issue 1, 375-382, January 7, 2005

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Production of Infectious SIVagm from Human Cells Requires Functional Inactivation but Not Viral Exclusion of Human APOBEC3G^*

Hiroaki Takeuchi, Sandra Kao, Eri Miyagi, Mohammad A. Khan, Alicia Buckler-White, Ron Plishka, and Klaus Strebel

From the Laboratory of Molecular Microbiology, NIAID, National Institutes of Health, Bethesda, Maryland 20892-0460

The virus infectivity factor (Vif) is a protein encoded by most primate lentiviruses. Recent evidence suggests that HIV-1 Vif reduces the intracellular levels of the host cytidine deaminase APOBEC3G (Apo3G) and inhibits its packaging into virions. These functions of Vif are thought to be species-specific. Accordingly, HIV-1 Vif can target only human Apo3G (hApo3G), whereas, African green monkey simian immunodeficiency virus (SIVagm) Vif can inhibit African green monkey but not human Apo3G. Consistent with this, we found that SIVagm Vif does not affect the stability of exogenously and endogenously expressed hApo3G and does not prevent packaging of exogenous and endogenous hApo3G into SIVagm virions. Nevertheless, SIVagm Vif supported spreading infection of SIVagm virus in the hApo3G-positive human A3.01 T cell line and rescued infectivity of viruses produced from Apo3G-expressing HeLa cells. Sequence analysis verified that SIVagm Vif inhibited the accumulation of hApo3G-induced mutations, suggesting that SIVagm Vif is indeed active in human cells. Our data suggest that SIVagm Vif can inhibit hApo3G activity without inducing its intracellular degradation or preventing its packaging into virions.

Received for publication, August 5, 2004 , and in revised form, October 14, 2004.

^* This work was supported in part by a grant from the National Institutes of Health Intramural AIDS Targeted Antiviral Program (to K. S.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Fig. 1.

To whom correspondence should be addressed: Laboratory of Molecular Microbiology, NIAID, National Institutes of Health, Bldg. 4, Rm. 310, 4 Center Dr., MSC 0460; Bethesda, MD 20892-0460. Tel.: 301-496-3132; Fax: 301-402-0226; E-mail: kstrebel{at}nih.gov.

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