Evolution of a species-specific determinant within human CRM1 that regulates the post-transcriptional phases of HIV-1 replication

The human immunodeficiency virus type-1 (hiv-1) rev protein regulates the nuclear export of intron-containing viral rnas by recruiting the crm1 nuclear export receptor. here,we employed a combination of functional and phylogenetic analyses to identify and characterize a species-specific determinant within human crm1 (hcrm1) that largely overcomes established defects in murine cells to the post-transcriptional stages of the hiv-1 life cycle. hcrm1 expression in murine cells promotes the cytoplasmic accumulation of intron-containing viral rnas,resulting in a substantial stimulation of the net production of infectious hiv-1 particles. these stimulatory effects require a novel surface-exposed element within heat repeats 9a and 10a,discrete from the binding cleft previously shown to engage rev's leucine-rich nuclear export signal. moreover,we show that this element is a unique feature of higher primate crm1 proteins,and discuss how this sequence has evolved from a non-functional,ancestral sequence. © 2011 sherer et al.