Sherer, NM;
Swanson, CM;
Hué, S;
Roberts, RG;
Bergeron, JR;
Malim, MH;
(2011)
Evolution of a species-specific determinant within human CRM1 that regulates the post-transcriptional phases of HIV-1 replication.
PLoS Pathog
, 7
(11)
, Article e1002395. 10.1371/journal.ppat.1002395.
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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.
| Type: | Article |
|---|---|
| Title: | Evolution of a species-specific determinant within human CRM1 that regulates the post-transcriptional phases of HIV-1 replication. |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.ppat.1002395 |
| Publisher version: | http://dx.doi.org/10.1371/journal.ppat.1002395 |
| Language: | English |
| Additional information: | © 2011 Sherer et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by the U.K. Medical Research Council. N.M.S. is a Long-Term Fellow (ALTF 176–2007) of the European Molecular Biology Organization and C.M.S. is a Research Councils U.K. Academic Fellow. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. |
| Keywords: | Amino Acid Sequence, Animals, Evolution, Molecular, HIV-1, Humans, Karyopherins, Mice, Models, Molecular, Molecular Sequence Data, NIH 3T3 Cells, Primates, Protein Structure, Tertiary, Receptors, Cytoplasmic and Nuclear, Repetitive Sequences, Nucleic Acid, Sequence Alignment, Species Specificity, Virus Replication, rev Gene Products, Human Immunodeficiency Virus |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1337639 |
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