ArticleMicrobiology spectrum2025
STING-mediated antiviral response: insights into MVA replication control in avian cells.
Article in Microbiology spectrum, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
The safety-tested Modified Vaccinia virus Ankara (MVA) is a well-characterized mutant virus widely used in fundamental research to elucidate the functions of Poxvirus host-interaction factors. Beyond its safety profile, MVA is an attractive viral vector for vaccine development due to its genetic stability and ability to efficiently infect antigen-presenting cells, such as dendritic cells and tumor cells. In this report, we investigated the interplay between MVA and the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) antiviral pathway in chicken fibroblast cell lines (wild-type DF-1 and knock-out STING) to verify whether manipulation of the STING axis could impact MVA replication and cell responses. Our findings demonstrate that STING-mediated signaling plays a role in contrasting the replication of MVA. Upon MVA infection, the loss of STING hampered the expression of type I interferons (IFNs) and, in turn, interferon-stimulated gene 15 (ISG15) and interferon-induced transmembrane protein 3 (IFITM3). In line with these results, the expression of early and late MVA genes was enhanced, and DNA replication occurred earlier and was more abundant. Interferon regulatory factor 1 (IRF1) and myeloid differentiation primary response 88 (MyD88) were significantly induced by MVA infection in STING-KO cells, indicating that their responses to MVA infection are independent of the cGAS/STING axis. Collectively, these results refine our knowledge of MVA-host interaction in chicken fibroblasts and offer insights to guide strategies for enhancing Poxvirus vaccine vector production.IMPORTANCEGiven the context-dependent nature of STING antiviral activity, it is critical to broaden the investigation in order to clarify the virus-host response mechanisms across different species, particularly in chicken fibroblasts, to provide insights into MVA-based vaccine production improvements.
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