RNA-Seq-based investigation of interferon-mediated antiviral activity of chlorophyll a from Tetraselmis sp.

<i>Tetraselmis</i> sp., a marine microalga amenable to mass cultivation, possesses antiviral properties, partly attributed to chlorophyll a. However, the underlying antiviral mechanisms remain poorly characterized. In this study, we investigated the antiviral activity and mode of action of chlorophyll a derived from <i>Tetraselmis</i> sp. by performing transcriptomic analyses on three experimental groups: untreated, uninfected cells; Zika virus (ZIKV)-infected cells; and chlorophyll a-treated, ZIKV-infected cells. Treatment with 5 µM chlorophyll a induced differential expression of genes associated with interferon-inducible antiviral responses. Gene ontology analysis revealed significant enrichment of biological processes such as "response to external stimulus" and "response to biotic stimulus." Notably, Venn diagram analysis of 130 differentially expressed genes (DEGs) demonstrated restoration of key interferon-stimulated genes, including interferon-induced protein with tetratricopeptide repeats (IFIT)1, IFIT2, IFIT3, and IFIT5, which was further validated by quantitative PCR and immunocytochemistry. These findings suggest that chlorophyll a from <i>Tetraselmis</i> sp. exerts antiviral effects primarily through modulation of interferon-mediated pathways. See also the graphical abstract(Fig. 1).