Nasal symbiont Staphylococcus epidermidis restricts influenza A virus replication via the creation of a polyamine-deficient cellular environment

鼻腔共生菌表皮葡萄球菌通过创造缺乏多胺的细胞环境来限制甲型流感病毒的复制

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作者:Ara Jo #, Kyeong-Seog Kim #, Jina Won, Haeun Shin, Sujin Kim, Bora Kim, Da Jung Kim, Joo-Youn Cho #, Hyun Jik Kim #

Abstract

Studies on the immune-regulatory roles played by the commensal microbes residing in the nasal mucosa consider the contribution of antiviral immune responses. Here, we sought to identify the nasal microbiome, Staphylococcus epidermidis-regulated antiviral immune responses and the alteration of polyamine metabolites in nasal epithelium. We found that polyamines were required for the life cycle of influenza A virus (IAV) and depletion of polyamines disturbed IAV replication in normal human nasal epithelial (NHNE) cells. Inoculation of S. epidermidis also suppressed IAV infection and the concentration of polyamines including putrescine, spermidine, and spermine was completely attenuated in S. epidermidis-inoculated NHNE cells. S. epidermidis activated the enzyme involved in the production of ornithine from arginine and downregulated the activity of the enzyme involved in the production of putrescine from ornithine in nasal epithelium. S. epidermidis also induced the activation of enzymes that promote the extracellular export of spermine and spermidine in NHNE cells. Our findings demonstrate that S. epidermidis is shown to be able of creating an intracellular environment lacking polyamines in the nasal epithelium and promote the balance of cellular polyamines in favor of the host to restrict influenza virus replication.

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