Basic residues in human immunodeficiency virus type 1 nucleocapsid promotevirion assembly via interaction with RNA

Retroviral Gag polyproteins drive virion assembly by polymerizing to form a spherical shell that lines the inner membrane of nascent virions. Deletion of the nucleocapsid (NC) domain of the Gag polyprotein disrupts assembly p resumably because NC is required for polymerization. Human immunodeficiency virus type I NC possesses two zinc finger motifs that are required for spe cific recognition and packaging of viral genomic RNA. Though essential, zin c fingers and genomic RNA are not required for virion assembly. NC promiscu ously associates with cellular RNAs, many of which are incorporated into vi rions. It has been hypothesized that Gag polymerization and virion assembly are promoted by nonspecific interaction of NC with RNA. Consistent with th is model, we found an inverse relationship between the number of NC basic r esidues replaced with alanine and NCs nonspecific RNA-binding activity, Gag 's ability to polymerize in vitro and in vivo, and Gag's capacity to assemb le virions. In contrast, mutation of NC's zinc fingers had only minor effec ts on these properties.