Journal article
TRIM5α restricts poxviruses and is antagonized by CypA and viral protein C6
- Abstract:
- Human tripartite motif protein 5a (TRIM5α) is a well-characterised restriction factor for some RNA viruses including HIV, but against DNA viruses reports are limited. Here, we demonstrate TRIM5α also restricts orthopoxviruses and, via its SPRY domain, binds the orthopoxvirus capsid protein L3 to diminish virus replication and activate innate immunity. In response, several orthopoxviruses, including vaccinia, rabbitpox, cowpox, monkeypox, camelpox and variola viruses, deploy countermeasures. First, protein C6 binds to TRIM5 via the RING domain to induce its proteasome-dependent degradation. Second, cyclophilin A (CypA) is recruited via interaction with capsid protein L3 to virus factories and virions to antagonise TRIM5α, and this interaction is prevented by cyclosporine A (CsA) and non-immunosuppressive derivatives alisporivir and NIM811. Both the proviral effect of CypA and antiviral effect of CsA are TRIM5α-dependent. CsA, alisporivir and NIM811 have antiviral activity against orthopoxviruses and since these drugs target a cellular protein, CypA, emergence of virus drug resistance is difficult. These results warrant testing of CsA derivatives against orthopoxviruses including monkeypox and variola.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
Actions
Access Document
- Files:
-
-
(Preview, Version of record, pdf, 10.4MB, Terms of use)
-
- Publisher copy:
- 10.1038/s41586-023-06401-0
Authors
- Publisher:
- Springer Nature
- Journal:
- Nature More from this journal
- Volume:
- 620
- Pages:
- 873-880
- Publication date:
- 2023-08-09
- Acceptance date:
- 2023-07-04
- DOI:
- EISSN:
-
1476-4687
- ISSN:
-
0028-0836
- Language:
-
English
- Keywords:
- Pubs id:
-
1495351
- Local pid:
-
pubs:1495351
- Deposit date:
-
2023-07-24
Terms of use
- Copyright holder:
- Zhao et al.
- Copyright date:
- 2023
- Rights statement:
- Copyright © 2023, The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
- Licence:
- CC Attribution (CC BY)
If you are the owner of this record, you can report an update to it here: Report update to this record