Human immunodeficiency virus type I Vif protein is packaged into the nucleoprotein complex through an interaction with viral genomic RNA

The human immunodeficiency virus type 1 (HIV-1) Vif protein plays a critica l role in the production of infectious virions. Previous studies have demon strated the presence of small amounts of Vif in virus particles. However, V if packaging was assumed to be nonspecific, and its functional significance has been questioned. We now report that packaging of Vif is dependent on t he packaging of viral genomic RNA in both permissive and restrictive HIV-1 target cells. Mutations in the nucleocapsid zinc finger domains that abroga te 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 abol ished packaging of Vif into virions. Virion-associated Vif was resistant to detergent extraction and copurified with components of the viral nucleopro tein complex and functional reverse transcription complexes. Thus, Vif is s pecifically packaged into virions as a component of the viral nucleoprotein complex. Our data suggest that the specific association of Vif with the vi ral nucleoprotein complex might be functionally significant and could be a critical requirement for infectivity of viruses produced from restrictive h ost cells.