Related Experiment Video
Updated: Jun 14, 2026
Arbovirus Infections As Screening Tools for the Identification of Viral Immunomodulators and Host Antiviral Factors
Published on: September 13, 2018
Identification of TRIM21 and TRIM14 as Antiviral Factors Against Langat and Zika Viruses
Pham-Tue-Hung Tran1, Mir Himayet Kabir2, Naveed Asghar1
1School of Medical Science, Faculty of Medicine and Health, Örebro University, SE-70362 Örebro, Sweden.
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.
Insights
Tripartite motif-containing proteins (TRIMs) like TRIM21 and TRIM14 restrict flavivirus infections by mediating interferon responses. These TRIMs are crucial in controlling Zika virus and Langat virus replication.
Area of Science:
- Virology
- Immunology
- Cell Biology
Background:
- Flaviviruses cause severe human diseases transmitted by mosquitoes and ticks.
- Intracellularly, flaviviruses induce endoplasmic reticulum (ER) membrane remodeling for viral replication complex scaffolding.
Purpose of the Study:
- To identify host proteins enriched in ER membranes during flavivirus infection.
- To investigate the role of enriched tripartite motif-containing proteins (TRIMs) in flavivirus restriction.
Main Methods:
- Purification of ER membrane fractions from virus-infected cells.
- Proteomic analysis to identify enriched proteins.
- Characterization of TRIM protein function and localization during flavivirus infection.
- Interferon response assays and viral replication studies.
Main Results:
- TRIM38, TRIM21, and TRIM14 were significantly enriched during infection with mosquito-borne (West Nile virus, Zika virus) and tick-borne (Langat virus) flaviviruses.
- TRIM21 and TRIM14 restricted Zika virus (ZIKV) and Langat virus (LGTV) replication, while TRIM38 hindered ZIKV infection.
- These TRIMs function as interferon-stimulated genes, mediating the type I interferon (IFN-I) response against ZIKV and LGTV.
- TRIM14 and TRIM38 colocalized with ZIKV NS3, and TRIM14 with LGTV NS3 and NS5, suggesting targeted antiviral mechanisms.
- TRIM21's antiviral activity against ZIKV and LGTV did not depend on direct interaction with viral NS3 or NS5 proteins.
Conclusions:
- TRIM38, TRIM21, and TRIM14 are host restriction factors that limit flavivirus replication.
- TRIM proteins mediate antiviral immunity through IFN-I responses and potentially direct interactions with viral proteins.
- TRIM21 and TRIM14 show potential as therapeutic targets for flavivirus infections.
