Evolution of a Species-Specific Determinant within Human CRM1 that Regulates the Post-transcriptional Phases of HIV-1 Replication

PLoS Pathogens

Julien R. C. Bergeron¹  Michael H. Malim²  Chad M. Swanson²  Nathan M. Sherer²  Roland G. Roberts³  Stéphane Hué⁴ 

[1] Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada;Department of Infectious Diseases, King's College London School of Medicine, London, United Kingdom;Department of Medical and Molecular Genetics, King's College London School of Medicine, London, United Kingdom;MRC/UCL Centre for Medical Molecular Virology, Division of Infection and Immunity, University College London, London, United Kingdom

关键词: HIV-1;    NIH 3T3 cells;    Primates;    Enzyme-linked immunoassays;    Cell membranes;    Rodents;    Protein sequencing;    Animal phylogenetics;   

DOI  :  10.1371/journal.ppat.1002395

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY