Venezuelan Equine Encephalitis Virus Antagonizes the cGAS-STING Pathway.
| Title: | Venezuelan Equine Encephalitis Virus Antagonizes the cGAS-STING Pathway. |
|---|---|
| Authors: | Heath BN; Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.; Center for Emerging, Zoonotic, and Arthropod-Borne Pathogens, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.; Akhrymuk M; Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.; Jamiu AT; Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.; Center for Emerging, Zoonotic, and Arthropod-Borne Pathogens, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.; Akhrymuk I; Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.; Pickrell AM; School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.; Kehn-Hall K; Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.; Center for Emerging, Zoonotic, and Arthropod-Borne Pathogens, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. |
| Source: | Cells [Cells] 2026 Feb 10; Vol. 15 (4). Date of Electronic Publication: 2026 Feb 10. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: MDPI Country of Publication: Switzerland NLM ID: 101600052 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4409 (Electronic) Linking ISSN: 20734409 NLM ISO Abbreviation: Cells Subsets: MEDLINE; In Process |
| Imprint Name(s): | Original Publication: Basel, Switzerland : MDPI |
| Abstract: | Venezuelan equine encephalitis virus (VEEV) is a mosquito-borne pathogen causing low mortality but high morbidity in humans, with 4-14% cases exhibiting neurological complications. While the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway is canonically associated with double-stranded DNA (dsDNA) detection, it has been shown to respond to RNA viruses and subsequently limit viral pathogenesis. Several viruses antagonize this signaling cascade, underscoring the importance that cGAS-STING plays in host immunity. Previous studies regarding single-stranded RNA viruses revealed that cGAS-STING limits viral replication in Old World alphavirus chikungunya virus infections, but little is known about New World alphaviruses such as VEEV. Here, we investigate the impact that STING activation has on VEEV infection as a potential prophylactic and therapeutic intervention. VEEV infection alone did not induce STING phosphorylation at Ser366, but interferon-stimulated genes (ISGs) were upregulated during the late phase of infection. Loss of STING through siRNA showed a partial dependency on STING for ISG transcription, suggesting that STING activation may occur through a noncanonical process. Priming of the STING pathway prior to infection was found to be critical in limiting viral replication; however, targeting STING activation post-infection abrogated the antiviral effects that dsDNA had on VEEV. VEEV suppressed STING phosphorylation in a multiplicity of infection (MOI)-dependent manner with the most robust pSTING (Ser366) inhibition observed at an MOI of 10. Collectively, our results suggest that VEEV antagonizes canonical STING activation. |
| Grant Information: | 7004199 United States Department of Agriculture; None Fralin Life Science Institute - Neurotrauma Research Program |
| Contributed Indexing: | Keywords: EEEV; Type I interferon; VEEV; alphavirus; cGAS-STING |
| Entry Date(s): | Date Created: 20260226 Latest Revision: 20260228 |
| Update Code: | 20260228 |
| PubMed Central ID: | PMC12939000 |
| DOI: | 10.3390/cells15040327 |
| PMID: | 41744770 |
| Database: | MEDLINE |
Journal Article