This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Khan, M. A. Articles by Strebel, K. Search for Related Content PubMed PubMed Citation Articles by Khan, M. A. Articles by Strebel, K.

 Previous Article  |  Next Article 

Journal of Virology, September 2002, p. 9112-9123, Vol. 76, No. 18
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.18.9112-9123.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Intravirion Processing of the Human Immunodeficiency Virus Type 1 Vif Protein by the Viral Protease May Be Correlated with Vif Function

Mohammad A. Khan,^1,2 Hirofumi Akari,^1,2 Sandra Kao,^1,2 Claudia Aberham,^1, David Davis,³ Alicia Buckler-White,¹ and Klaus Strebel^1,2*

Laboratory of Molecular Microbiology,¹ Viral Biochemistry Section, National Institute of Allergy and Infectious Diseases,² HIV Malignancy Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892³

Received 4 April 2002/ Accepted 12 June 2002

The human immunodeficiency virus type 1 (HIV-1) Vif protein is specifically packaged into virus particles through an interaction with viral genomic RNA in which it associates with the viral nucleoprotein complex. We now demonstrate for the first time that virus-associated Vif is subject to proteolytic processing by the viral protease (Pr). Pr-dependent processing of Vif was observed both in vivo and in vitro. In vivo processing of Vif was cell type independent and evident by the appearance of a 7-kDa processing product, which was restricted to cell-free virus preparations. Processing of Vif required an active viral Pr and was sensitive to Pr inhibitors such as ritonavir. The processing site in Vif was characterized both in vivo and in vitro and mapped to Ala₁₅₀. Interestingly, the Vif processing site is located in a domain that is highly conserved among HIV-1, HIV-2, and simian immunodeficiency virus Vif isolates. Mutations at or near the processing site did not affect protein stability or packaging efficiency but had dramatic effects on Vif processing. In general, mutations that markedly increased or decreased the sensitivity of Vif to proteolytic processing severely impaired or completely abolished Vif function. In contrast, mutations at the same site that had little or no effect on processing efficiency also did not influence Vif function. None of the mutants affected the ability of the virus to replicate in permissive cell lines. Our data suggest that mutations in Vif that cause a profound change in the sensitivity to Pr-dependent processing also severely impaired Vif function, suggesting that intravirion processing of Vif is important for the production of infectious viruses.

Present address: Baxter AG, PC/Molecular Biology, A-1220 Vienna, Austria.

This article has been cited by other articles:

• Rue, S. M., Roos, J. W., Tarwater, P. M., Clements, J. E., Barber, S. A. (2005). Phosphorylation and Proteolytic Cleavage of Gag Proteins in Budded Simian Immunodeficiency Virus. J. Virol. 79: 2484-2492 [Abstract] [Full Text]  
• Feng, F., Davis, A., Lake, J.-A., Carr, J., Xia, W., Burrell, C., Li, P. (2004). Ring Finger Protein ZIN Interacts with Human Immunodeficiency Virus Type 1 Vif. J. Virol. 78: 10574-10581 [Abstract] [Full Text]  
• Akari, H., Fujita, M., Kao, S., Khan, M. A., Shehu-Xhilaga, M., Adachi, A., Strebel, K. (2004). High Level Expression of Human Immunodeficiency Virus Type-1 Vif Inhibits Viral Infectivity by Modulating Proteolytic Processing of the Gag Precursor at the p2/Nucleocapsid Processing Site. J. Biol. Chem. 279: 12355-12362 [Abstract] [Full Text]  
• Kao, S., Khan, M. A., Miyagi, E., Plishka, R., Buckler-White, A., Strebel, K. (2003). The Human Immunodeficiency Virus Type 1 Vif Protein Reduces Intracellular Expression and Inhibits Packaging of APOBEC3G (CEM15), a Cellular Inhibitor of Virus Infectivity. J. Virol. 77: 11398-11407 [Abstract] [Full Text]  
• Kao, S., Akari, H., Khan, M. A., Dettenhofer, M., Yu, X.-F., Strebel, K. (2002). Human Immunodeficiency Virus Type 1 Vif Is Efficiently Packaged into Virions during Productive but Not Chronic Infection. J. Virol. 77: 1131-1140 [Abstract] [Full Text]