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Volume 17
Issue 5
10.3390/v17050644
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Identification of TRIM21 and TRIM14 as Antiviral Factors Against Langat and Zika Viruses

by
Pham-Tue-Hung Tran
1,†,
Mir Himayet Kabir
2,†,
Naveed Asghar
1,
Matthew R. Hathaway
2,
Assim Hayderi
1,
Roger Karlsson
3,4,
Anders Karlsson
5,
Travis Taylor
2,
Wessam Melik
1 and
Magnus Johansson
1,*
1
School of Medical Science, Faculty of Medicine and Health, Örebro University, SE-70362 Örebro, Sweden
2
Department of Medical Microbiology and Immunology, College of Medicine and Life Sciences, University of Toledo, Toledo, OH 43612, USA
3
Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy of the University of Gothenburg, SE-40234 Gothenburg, Sweden
4
Department of Clinical Microbiology, Sahlgrenska University Hospital, SE-41346 Gothenburg, Sweden
5
Nanoxis Consulting AB, SE-40016 Gothenburg, Sweden
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Viruses 2025, 17(5), 644; https://doi.org/10.3390/v17050644 (registering DOI)
Submission received: 19 February 2025 / Revised: 16 April 2025 / Accepted: 18 April 2025 / Published: 29 April 2025
(This article belongs to the Special Issue Advances in Alphavirus and Flavivirus Research, 2nd Edition)
Versions Notes

Abstract

Flaviviruses are usually transmitted to humans via mosquito or tick bites, whose infections may lead to severe diseases and fatality. During intracellular infection, they remodel the endoplasmic reticulum (ER) membrane to generate compartments scaffolding the replication complex (RC) where replication of the viral genome takes place. In this study, we purified the ER membrane fraction of virus infected cells to identify the proteins that were enriched during flavivirus infection. We found that tripartite motif-containing proteins (TRIMs) including TRIM38, TRIM21, and TRIM14 were significantly enriched during infection with mosquito-borne (West Nile virus strain Kunjin and Zika virus (ZIKV)) and tick-borne (Langat virus (LGTV)) flaviviruses. Further characterizations showed that TRIM21 and TRIM14 act as restriction factors against ZIKV and LGTV, while TRIM38 hinders ZIKV infection. These TRIMs worked as interferon-stimulated genes to mediate IFN-I response against LGTV and ZIKV infections. Restriction of ZIKV by TRIM14 and TRIM38 coincides with their colocalization with ZIKV NS3. TRIM14-mediated LGTV restriction coincides with its colocalization with LGTV NS3 and NS5 proteins. However, TRIM21 did not colocalize with ZIKV and LGTV NS3 or NS5 protein suggesting its antiviral activity is not dependent on direct targeting the viral enzyme. Finally, we demonstrated that overexpression of TRIM21 and TRIM14 restricted LGTV replication.
Keywords: flavivirus; antiviral host factor; TRIM14; TRIM21; TRIM38; ZIKV; LGTV; WNV; NS3; NS5 flavivirus; antiviral host factor; TRIM14; TRIM21; TRIM38; ZIKV; LGTV; WNV; NS3; NS5

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MDPI and ACS Style

Tran, P.-T.-H.; Kabir, M.H.; Asghar, N.; Hathaway, M.R.; Hayderi, A.; Karlsson, R.; Karlsson, A.; Taylor, T.; Melik, W.; Johansson, M. Identification of TRIM21 and TRIM14 as Antiviral Factors Against Langat and Zika Viruses. Viruses 2025, 17, 644. https://doi.org/10.3390/v17050644

AMA Style

Tran P-T-H, Kabir MH, Asghar N, Hathaway MR, Hayderi A, Karlsson R, Karlsson A, Taylor T, Melik W, Johansson M. Identification of TRIM21 and TRIM14 as Antiviral Factors Against Langat and Zika Viruses. Viruses. 2025; 17(5):644. https://doi.org/10.3390/v17050644

Chicago/Turabian Style

Tran, Pham-Tue-Hung, Mir Himayet Kabir, Naveed Asghar, Matthew R. Hathaway, Assim Hayderi, Roger Karlsson, Anders Karlsson, Travis Taylor, Wessam Melik, and Magnus Johansson. 2025. "Identification of TRIM21 and TRIM14 as Antiviral Factors Against Langat and Zika Viruses" Viruses 17, no. 5: 644. https://doi.org/10.3390/v17050644

APA Style

Tran, P.-T.-H., Kabir, M. H., Asghar, N., Hathaway, M. R., Hayderi, A., Karlsson, R., Karlsson, A., Taylor, T., Melik, W., & Johansson, M. (2025). Identification of TRIM21 and TRIM14 as Antiviral Factors Against Langat and Zika Viruses. Viruses, 17(5), 644. https://doi.org/10.3390/v17050644

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