Sequence-specific interaction between HIV-1 matrix protein and viral genomic RNA revealed by in vitro genetic selection

The human immunodeficiency virus type-1 matrix protein (HIV-1 MA) is a mult ifunctional structural protein synthesized as part of the Pr55 gag polyprot ein, We have used in vitro genetic selection to identify an RNA consensus s equence that specifically interacts with MA (K-d = 5 x 10(-7) M), This 13-n t MA binding consensus sequence bears a high degree of homology (77%) to a region (nt 1433-1446) within the POL open reading frame of the HIV-1 genome (consensus sequence from 38 HIV-1 strains). Chemical interference experime nts identified the nucleotides within the MA binding consensus sequence inv olved in direct contact with MA. We further demonstrate that this RNA-prote in interaction is mediated through a stretch of basic amino acids within MA . Mutations that disrupt the interaction between MA and its RNA binding sit e within the HIV-1 genome resulted in a measurable decrease in viral replic ation.