Price, AJ;
Fletcher, AJ;
Schaller, T;
Elliott, T;
Lee, K;
KewalRamani, VN;
Chin, JW;
... James, LC; + view all
(2012)
CPSF6 Defines a Conserved Capsid Interface that Modulates HIV-1 Replication.
PLOS PATHOGENS
, 8
(8)
, Article e1002896. 10.1371/journal.ppat.1002896.
![[thumbnail of 1370448.pdf]](https://discovery.ucl.ac.uk/style/images/fileicons/application_pdf.png) Preview |
PDF
1370448.pdf Download (4MB) |
Abstract
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.
| Type: | Article |
|---|---|
| Title: | CPSF6 Defines a Conserved Capsid Interface that Modulates HIV-1 Replication |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.ppat.1002896 |
| Publisher version: | http://dx.doi.org/10.1371/journal.ppat.1002896 |
| Language: | English |
| Additional information: | This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. Funding: Funding was provided by: Medical Research Council (U105181010: AJP, AJF, TS, TE, JWC, GJT, LCJ); European Research Council (ERC 281627 - IAI); Wellcome Trust; National Institute for Health Research UCL/UCLH Comprehensive Biomedical Research Centre; Emmanuel College, Cambridge; National Cancer Institute's intramural Center for Cancer Research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. |
| 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 UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1370448 |
Archive Staff Only
 |
View Item |
