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PLoS Pathog. 2011 Nov;7(11):e1002395. doi: 10.1371/journal.ppat.1002395. Epub 2011 Nov 17.

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

Author information

1
Department of Infectious Diseases, King's College London School of Medicine, London, United Kingdom.

Abstract

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.

PMID:
22114565
PMCID:
PMC3219727
DOI:
10.1371/journal.ppat.1002395
[Indexed for MEDLINE]
Free PMC Article

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