Teetering on the Edge: The Critical Role of RNA Processing Control During HIV-1 Replication

Abstract Regulation of RNA processing plays a central role in the replication of multiple mammalian viruses, in particular HIV-1. From a single 9 kb transcript, HIV-1 generates over 40 mRNAs through alternative RNA splicingto allow expression of its full coding capacity. Control of the amount of individual viral mRNAs produced is achieved through the combined effects of multiple host cell factors, most belonging to the heterogeneous nuclear ribonucleoproteinand serine–arginine protein familiesof splicing regulatory factors, interacting with positive or negative splicing regulatory sequenceswithin the HIV-1 genome. Understanding how such regulation is achieved offers promise of new insights into controlling this infection as disruption of select events has been found to have profound negative effects on its replication. In this review, we summarize the current state of knowledge of the factors involved in modulating HIV-1 RNA splicingand detail more recent description of small molecules that alter select events within this pathway to suppress replication of the virus.