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Journal of Virology, August 2001, p. 7252-7265, Vol. 75, No. 16
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.16.7252-7265.2001

Human Immunodeficiency Virus Type 1 Vif Protein Is Packaged into the Nucleoprotein Complex through an Interaction with Viral Genomic RNA

Mohammad A. Khan,1 Claudia Aberham,1,dagger Sandra Kao,1 Hirofumi Akari,1 Robert Gorelick,2 Stephan Bour,1 and Klaus Strebel1,*

Laboratory of Molecular Microbiology, Viral Biochemistry Section, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland 20892-0460,1 and AIDS Vaccine Program, SAIC Frederick, National Cancer Institute at Frederick, Frederick, Maryland 21702-12012

Received 26 January 2001/Accepted 15 May 2001

The human immunodeficiency virus type 1 (HIV-1) Vif protein plays a critical role in the production of infectious virions. Previous studies have demonstrated the presence of small amounts of Vif in virus particles. However, Vif packaging was assumed to be nonspecific, and its functional significance has been questioned. We now report that packaging of Vif is dependent on the packaging of viral genomic RNA in both permissive and restrictive HIV-1 target cells. Mutations in the nucleocapsid zinc finger domains that abrogate packaging of viral genomic RNA abolished packaging of Vif. Additionally, an RNA packaging-defective virus exhibited significantly reduced packaging of Vif. Finally, deletion of a putative RNA-interacting domain in Vif abolished packaging of Vif into virions. Virion-associated Vif was resistant to detergent extraction and copurified with components of the viral nucleoprotein complex and functional reverse transcription complexes. Thus, Vif is specifically packaged into virions as a component of the viral nucleoprotein complex. Our data suggest that the specific association of Vif with the viral nucleoprotein complex might be functionally significant and could be a critical requirement for infectivity of viruses produced from restrictive host cells.

* Corresponding author. Mailing address: NIH, NIAID, 4/312, 4 Center Dr., MSC 0460, Bethesda, MD 20892-0460. Phone: (301) 496-3132. Fax: (301) 402-0226. E-mail: kstrebel{at}nih.gov.

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

Journal of Virology, August 2001, p. 7252-7265, Vol. 75, No. 16
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.16.7252-7265.2001


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