TRPC1 participates in the HSV-1 infection process by facilitating viral entry

Mammalian transient receptor potential (TRP) channels are major components of Ca2+ signaling pathways and control a diversity of physiological functions. Here, we report a specific role for TRPC1 in the entry of herpes simplex virus type 1 (HSV-1) into cells. HSV-1-induced Ca2+ release and entry were dependent on Orai1, STIM1, and TRPC1. Inhibition of Ca2+ entry or knockdown of these proteins attenuated viral entry and infection. HSV-1 glycoprotein D interacted with the third ectodomain of TRPC1, and this interaction facilitated viral entry. Knockout of TRPC1 attenuated HSV-1-induced ocular abnormality and morbidity in vivo in TRPC1−/− mice. There was a strong correlation between HSV-1 infection and plasma membrane localization of TRPC1 in epithelial cells within oral lesions in buccal biopsies from HSV-1-infected patients. Together, our findings demonstrate a critical role for TRPC1 in HSV-1 infection and suggest the channel as a potential target for anti-HSV therapy.Fil: He, DongXu. Jiangnan University; ChinaFil: Mao, AiQin. Jiangnan University; ChinaFil: Li, YouRan. Jiangnan University; ChinaFil: Tam, SiuCheung. Chinese University Of Hong Kong; Hong KongFil: Zheng, YongTang. Kunming Institute Of Zoology Chinese Academy Of Sciences; ChinaFil: Yao, XiaoQiang. Chinese University Of Hong Kong; Hong KongFil: Birnbaumer, Lutz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Ambudkar, Indu S.. National Institute Of Dental And Craniofacial Research ; Estados UnidosFil: Ma, Xin. Jiangnan University; Chin