奥普提神经蛋白（Optineurin）通过促进干扰素介导的JAK/STAT信号通路来抑制寨卡病毒（ZIKV）的复制。

Abstract

Optineurin (OPTN) is a multifunctional adapter protein involved in several inflammatory and anti-viral signaling pathways. However, its role in Zika virus (ZIKV) infection remains unclear. This study aims to investigate the effect of OPTN on ZIKV replication and to elucidate the underlying molecular mechanisms. Differential expressions of OPTN during ZIKV infection were analyzed in both A549 and U251-MG cells. OPTN was overexpressed using an EGFP-OPTN plasmid, with an empty EGFP-N1 vector as a control. ZIKV NS5 mRNA and NS1 protein levels were quantified in A549 cells following ZIKV infection by qRT–PCR and Western blotting, respectively, while ZIKV capsid protein expression in U251-MG cells was assessed by immunofluorescence. The expression of type I interferons (IFNs), components of the JAK/STAT signaling pathway, and downstream interferon-stimulated genes (ISGs) were examined following OPTN overexpression during ZIKV infection. Interferon-stimulated response element (ISRE) activity was evaluated using a dual-luciferase reporter assay. And P-STAT1 was assessed by Western blotting. OPTN mRNA expression was significantly upregulated in both A549 and U251-MG cells in a dose-dependent manner following ZIKV infection. Overexpression of OPTN markedly inhibited ZIKV replication in both cell lines. Mechanistically, OPTN enhanced antiviral activity by inducing type I IFN expression, promoting STAT1 phosphorylation, and increasing ISRE activity. In addition, OPTN upregulated several antiviral ISGs, including MxA, IFIT1, and viperin. These findings identify OPTN as a critical host restricting factor to suppress ZIKV replication by promoting type I IFN-mediated JAK/STAT signaling pathway.