Downregulation of calcium-regulated heat stable protein 1 expression by low-temperature stimulation causes reduction of interferon-β expression and sensitivity to influenza viral infection

低温刺激下调钙调节热稳定蛋白1表达导致干扰素-β表达和对流感病毒感染的敏感性降低

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作者:Keisuke Nishioka, Tomo Daidoji, Takaaki Nakaya

Abstract

Influenza is prevalent in temperate countries during winter when the environment is dry and cold; however, in tropical and subtropical countries, it is prevalent during the hot, humid rainy season. Thus, temperature and humidity conditions affect influenza outbreaks in different climates. Although the reason for this may be related to host conditions and the conditions under which the virus can survive, it is difficult to analyze changes in host viral responses owing to environmental changes at the cellular level. In the current study, to find candidate genes related with temperature, we analyzed the effects of low-temperature stimulation on influenza virus infection using immortalized respiratory cell lines with the same genetic background established in our laboratory. Although two cell lines with different immune response strengths exhibited enhancement of influenza virus replication following low-temperature stimulation, the mechanisms and degrees were different. In cell lines that showed greater changes, promotion of viral replication was found to involve genes related to temperature, including TRPM2 and CARHSP1. In particular, CARHSP1 expression was decreased by low-temperature stimulation in several respiratory cell lines. In knockdown experiments, because reduction of interferon-β production and sensitivity were observed, the decline may create an environment in which the initial infection cannot be controlled. This procedure may be effective for identifying candidate genes related to the host/viral responses to changes in temperature, and these results can help elucidate the relationships of temperature, humidity, and host responses with viral infection.

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