Academic Journal
Restraint of Powassan virus replication by TRIM5α facilitates viral avoidance of antiviral immunity.
| Τίτλος: | Restraint of Powassan virus replication by TRIM5α facilitates viral avoidance of antiviral immunity. |
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| Συγγραφείς: | Broeckel RM; Laboratory of Virology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.; Dispatch Biotherapeutics, Philadelphia, PA, USA., Fitzmeyer EA; Laboratory of Virology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.; Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA., Chebishev E; Laboratory of Virology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA., Shannon JG; Innate Immunity and Pathogenesis Section, Laboratory of Neurological Infections and Immunity, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA., Shue B; Innate Immunity and Pathogenesis Section, Laboratory of Neurological Infections and Immunity, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA., Hage A; Innate Immunity and Pathogenesis Section, Laboratory of Neurological Infections and Immunity, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA., Spada S; Innate Immunity and Pathogenesis Section, Laboratory of Neurological Infections and Immunity, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.; Molecular Parasitology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Artikis E; TSE/Prion Biochemistry Section, Laboratory of Neurological Infections and Immunity, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA., Chiramel AI; Laboratory of Virology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.; Boehringer Ingelheim, Biberach, Germany., McNally KL; Laboratory of Virology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA., Larson CL; Innate Immunity and Pathogenesis Section, Laboratory of Neurological Infections and Immunity, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA., von Kutzleben M; Innate Immunity and Pathogenesis Section, Laboratory of Neurological Infections and Immunity, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA., Robertson SJ; Innate Immunity and Pathogenesis Section, Laboratory of Neurological Infections and Immunity, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA., Offerdahl DK; Biology of Vector-Borne Viruses Section, Laboratory of Virology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA., Lakin HA; Innate Immunity and Pathogenesis Section, Laboratory of Neurological Infections and Immunity, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA., Bloom ME; Biology of Vector-Borne Viruses Section, Laboratory of Virology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA., Kuhn S; Integrated Data Sciences Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Nair V; Reserch Technologies Section, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA., Eyre NS; School of Biological Sciences, University of Adelaide, Adelaide, SA, Australia.; College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia., Beard MR; School of Biological Sciences, University of Adelaide, Adelaide, SA, Australia., Grigg ME; Molecular Parasitology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Bouamr F; Molecular Parasitology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Best SM; Innate Immunity and Pathogenesis Section, Laboratory of Neurological Infections and Immunity, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA. sbest@niaid.nih.gov. |
| Πηγή: | Communications biology [Commun Biol] 2026 Jul 07. Date of Electronic Publication: 2026 Jul 07. |
| Publication Model: | Ahead of Print |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Nature Publishing Group UK Country of Publication: England NLM ID: 101719179 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2399-3642 (Electronic) Linking ISSN: 23993642 NLM ISO Abbreviation: Commun Biol Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: London, United Kingdom : Nature Publishing Group UK, [2018]- |
| Περίληψη: | TRIpartite Motif (TRIM) protein 5 alpha (TRIM5α) is a well-characterized cellular inhibitor of lentivirus replication that limits transmission of related viruses between primates. We previously reported that TRIM5α derived from humans and rhesus macaques inhibits replication of orthoflaviviruses belonging to the tick-borne encephalitis virus (TBEV) serocomplex, including TBEV, Kyasanur forest disease virus and Langat virus (LGTV), but interestingly not the tick-borne Powassan virus (POWV). To further characterize the primate TRIM5α and orthoflavivirus interface, we screened TRIM5α variants from representative old- and new-world primates for restriction capacity. TRIM5α from old-world African green monkey, De Brazza's monkey and chimpanzee demonstrated virus-specific restriction of tick-borne orthoflaviviruses. Efforts to determine why TRIM5α fails to inhibit POWV revealed that our lab stock had acquired a non-synonymous mutation in NS3 that, when introduced into a POWV molecular clone, facilitated virus replication in the presence of all inhibitory primate TRIM5α proteins. Infection of human dendritic cells with TRIM5α-resistant POWV resulted in high early replication and strong induction of interferon responses that limited replication compared with the wild-type virus. Thus, primate TRIM5α functions as a potent cellular barrier to infection with tick-borne orthoflaviviruses that restrains replication to a level that may help avoid early innate immune recognition. (© 2026. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.) |
| Competing Interests: | Competing interests: The authors declare no competing interests. |
| Σχόλια: | Update of: bioRxiv. 2026 Mar 16:2026.03.15.711935. doi: 10.64898/2026.03.15.711935.. (PMID: 42051304) |
| Entry Date(s): | Date Created: 20260706 Latest Revision: 20260714 |
| Update Code: | 20260714 |
| DOI: | 10.1038/s42003-026-10613-1 |
| PMID: | 42410041 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 2399-3642 |
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| DOI: | 10.1038/s42003-026-10613-1 |