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...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-11-01
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| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1002395&type=printable |
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| author | Nathan M Sherer Chad M Swanson Stéphane Hué Roland G Roberts Julien R C Bergeron Michael H Malim |
| author_facet | Nathan M Sherer Chad M Swanson Stéphane Hué Roland G Roberts Julien R C Bergeron Michael H Malim |
| author_sort | Nathan M Sherer |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-bf378b1154e44d0d9d60f786ff92681c |
| institution | Kabale University |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2011-11-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-bf378b1154e44d0d9d60f786ff92681c2025-08-20T03:46:05ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742011-11-01711e100239510.1371/journal.ppat.1002395Evolution of a species-specific determinant within human CRM1 that regulates the post-transcriptional phases of HIV-1 replication.Nathan M ShererChad M SwansonStéphane HuéRoland G RobertsJulien R C BergeronMichael H MalimThe 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.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1002395&type=printable |
| spellingShingle | Nathan M Sherer Chad M Swanson Stéphane Hué Roland G Roberts Julien R C Bergeron Michael H Malim Evolution of a species-specific determinant within human CRM1 that regulates the post-transcriptional phases of HIV-1 replication. PLoS Pathogens |
| title | Evolution of a species-specific determinant within human CRM1 that regulates the post-transcriptional phases of HIV-1 replication. |
| title_full | Evolution of a species-specific determinant within human CRM1 that regulates the post-transcriptional phases of HIV-1 replication. |
| title_fullStr | Evolution of a species-specific determinant within human CRM1 that regulates the post-transcriptional phases of HIV-1 replication. |
| title_full_unstemmed | Evolution of a species-specific determinant within human CRM1 that regulates the post-transcriptional phases of HIV-1 replication. |
| title_short | Evolution of a species-specific determinant within human CRM1 that regulates the post-transcriptional phases of HIV-1 replication. |
| title_sort | evolution of a species specific determinant within human crm1 that regulates the post transcriptional phases of hiv 1 replication |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1002395&type=printable |
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