title: Evolution of a species-specific determinant within human CRM1 that regulates the post-transcriptional phases of HIV-1 replication.
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.
authors: Department of Infectious Diseases, King's College London School of Medicine, London, United Kingdom.
authors: Nathan M
authors: NM
authors: Sherer
authors: Chad M
authors: CM
authors: Swanson
authors: Stéphane
authors: S
authors: Hué
authors: Roland G
authors: RG
authors: Roberts
authors: Julien R C
authors: JR
authors: Bergeron
authors: Michael H
authors: MH
authors: Malim
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019143:Evolution, Molecular; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D028884:Karyopherins / Q000737:chemistry / Q000235:genetics*; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D011323:Primates / Q000235:genetics; D017434:Protein Structure, Tertiary; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D016415:Sequence Alignment; D013045:Species Specificity; D014779:Virus Replication / Q000235:genetics*; D054321:rev Gene Products, Human Immunodeficiency Virus / Q000235:genetics*; D000097606:Exportin 1 Protein
chemical_list: D028884:Karyopherins; D018160:Receptors, Cytoplasmic and Nuclear; D054321:rev Gene Products, Human Immunodeficiency Virus; D000097606:Exportin 1 Protein; C514860:rev protein, Human Immunodeficiency Virus-1