Abstract
The human immunodeficiency virus type-1 matrix protein
(HIV-1 MA) is a multifunctional structural protein synthesized
as part of the Pr55 gag polyprotein. We have used in vitro
genetic selection to identify an RNA consensus sequence that
specifically interacts with MA (Kd
= 5 × 10−7 M). This 13-nt 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 experiments identified
the nucleotides within the MA binding consensus sequence
involved in direct contact with MA. We further demonstrate
that this RNA–protein interaction is mediated through
a stretch of basic amino acids within MA. Mutations that
disrupt the interaction between MA and its RNA binding
site within the HIV-1 genome resulted in a measurable decrease
in viral replication.
