CPSF6 defines a conserved capsid interface that modulates HIV-1 replication.
The HIV-1 genome enters cells inside a shell comprised of capsid (CA) protein. Variation in CA sequence alters HIV-1 infectivity and escape from host restriction factors. However, apart from the Cyclophilin A-binding loop, CA has no known interfaces with which to interact with cellular cofactors. He...
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| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1002896&type=printable |
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| _version_ | 1849434143420579840 |
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| author | Amanda J Price Adam J Fletcher Torsten Schaller Tom Elliott KyeongEun Lee Vineet N KewalRamani Jason W Chin Greg J Towers Leo C James |
| author_facet | Amanda J Price Adam J Fletcher Torsten Schaller Tom Elliott KyeongEun Lee Vineet N KewalRamani Jason W Chin Greg J Towers Leo C James |
| author_sort | Amanda J Price |
| collection | DOAJ |
| description | The HIV-1 genome enters cells inside a shell comprised of capsid (CA) protein. Variation in CA sequence alters HIV-1 infectivity and escape from host restriction factors. However, apart from the Cyclophilin A-binding loop, CA has no known interfaces with which to interact with cellular cofactors. Here we describe a novel protein-protein interface in the N-terminal domain of HIV-1 CA, determined by X-ray crystallography, which mediates both viral restriction and host cofactor dependence. The interface is highly conserved across lentiviruses and is accessible in the context of a hexameric lattice. Mutation of the interface prevents binding to and restriction by CPSF6-358, a truncated cytosolic form of the RNA processing factor, cleavage and polyadenylation specific factor 6 (CPSF6). Furthermore, mutations that prevent CPSF6 binding also relieve dependence on nuclear entry cofactors TNPO3 and RanBP2. These results suggest that the HIV-1 capsid mediates direct host cofactor interactions to facilitate viral infection. |
| format | Article |
| id | doaj-art-7ebe256ec2ca4132a1a8a19a34467a08 |
| institution | Kabale University |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-7ebe256ec2ca4132a1a8a19a34467a082025-08-20T03:26:47ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742012-01-0188e100289610.1371/journal.ppat.1002896CPSF6 defines a conserved capsid interface that modulates HIV-1 replication.Amanda J PriceAdam J FletcherTorsten SchallerTom ElliottKyeongEun LeeVineet N KewalRamaniJason W ChinGreg J TowersLeo C JamesThe HIV-1 genome enters cells inside a shell comprised of capsid (CA) protein. Variation in CA sequence alters HIV-1 infectivity and escape from host restriction factors. However, apart from the Cyclophilin A-binding loop, CA has no known interfaces with which to interact with cellular cofactors. Here we describe a novel protein-protein interface in the N-terminal domain of HIV-1 CA, determined by X-ray crystallography, which mediates both viral restriction and host cofactor dependence. The interface is highly conserved across lentiviruses and is accessible in the context of a hexameric lattice. Mutation of the interface prevents binding to and restriction by CPSF6-358, a truncated cytosolic form of the RNA processing factor, cleavage and polyadenylation specific factor 6 (CPSF6). Furthermore, mutations that prevent CPSF6 binding also relieve dependence on nuclear entry cofactors TNPO3 and RanBP2. These results suggest that the HIV-1 capsid mediates direct host cofactor interactions to facilitate viral infection.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1002896&type=printable |
| spellingShingle | Amanda J Price Adam J Fletcher Torsten Schaller Tom Elliott KyeongEun Lee Vineet N KewalRamani Jason W Chin Greg J Towers Leo C James CPSF6 defines a conserved capsid interface that modulates HIV-1 replication. PLoS Pathogens |
| title | CPSF6 defines a conserved capsid interface that modulates HIV-1 replication. |
| title_full | CPSF6 defines a conserved capsid interface that modulates HIV-1 replication. |
| title_fullStr | CPSF6 defines a conserved capsid interface that modulates HIV-1 replication. |
| title_full_unstemmed | CPSF6 defines a conserved capsid interface that modulates HIV-1 replication. |
| title_short | CPSF6 defines a conserved capsid interface that modulates HIV-1 replication. |
| title_sort | cpsf6 defines a conserved capsid interface that modulates hiv 1 replication |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1002896&type=printable |
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