Context-dependent phenotype of a human immunodeficiency virus type 1 nucleocapsid mutation

The human immunodeficiency virus type 1 (HIV-1) nucleocapsid mutation R10A/ K11A abolishes viral replication when present in proviral clone HIV-1(HXB-2 ), but it was found to have minimal effect on replication of the closely re lated HIV-1(NL4-3). Functional mapping demonstrated that a nonconservative amino acid change at nucleocapsid residue 24 (threonine in HIV-1(HXB-2) iso leucine in HIV-1(NL4-3)) is the major determinant of the different R10A/K11 A phenotypes in these two proviruses, Threonine-isoleucine exchanges appear to modify the R10A/K11A phenotype via effects on virion RNA-packaging effi ciency. The improved packaging seen with hydrophobic isoleucine is consiste nt with solution structures localizing this residue to a hydrophobic pocket that contacts guanosine bases in viral genomic RNA stem-loops critical for packaging.