title: Herpes Simplex Virus 1 Suppresses the Function of Lung Dendritic Cells via Caveolin-1.
abstract: Caveolin-1 (Cav-1), the principal structural protein of caveolae, has been implicated as a regulator of virus-host interactions. Several viruses exploit caveolae to facilitate viral infections. However, the roles of Cav-1 in herpes simplex virus 1 (HSV-1) infection have not fully been elucidated. Here, we report that Cav-1 downregulates the expression of inducible nitric oxide synthase (iNOS) and the production of nitric oxide (NO) in dendritic cells (DCs) during HSV-1 infection. As a result, Cav-1 deficiency led to an accelerated elimination of virus and less lung pathological change following HSV-1 infection. This protection was dependent on iNOS and NO production in DCs. Adoptive transfer of DCs with Cav-1 knockdown was sufficient to confer the protection to wild-type (WT) mice. In addition, Cav-1 knockout (KO) (Cav-1(-/-)) mice treated with an iNOS inhibitor exhibited significantly reduced survival compared to that of the nontreated controls. We found that Cav-1 colocalized with iNOS and HSV-1 in caveolae in HSV-1-infected DCs, suggesting their interaction. Taken together, our results identified Cav-1 as a novel regulator utilized by HSV-1 to evade the host antiviral response mediated by NO production. Therefore, Cav-1 might be a valuable target for therapeutic approaches against herpesvirus infections.
authors.affiliation: State Key Laboratory for Agro-Biotechnology, College of Biological Science, China Agricultural University, Beijing, People's Republic of China.
authors.forename: Bing
authors.initials: B
authors.lastname: Wu
authors.affiliation: Key Laboratory of Medical Molecular Virology of MOH and MOE, Fudan University Shanghai Medical College, Shanghai, People's Republic of China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Geng
authors.affiliation: State Key Laboratory for Agro-Biotechnology, College of Biological Science, China Agricultural University, Beijing, People's Republic of China.
authors.forename: Yanmin
authors.initials: Y
authors.lastname: Bi
authors.affiliation: State Key Laboratory for Agro-Biotechnology, College of Biological Science, China Agricultural University, Beijing, People's Republic of China.
authors.forename: Hu
authors.initials: H
authors.lastname: Liu
authors.affiliation: College of Veterinary Medicine, China Agricultural University, Beijing, People's Republic of China.
authors.forename: Yanxin
authors.initials: Y
authors.lastname: Hu
authors.affiliation: State Key Laboratory for Agro-Biotechnology, College of Biological Science, China Agricultural University, Beijing, People's Republic of China.
authors.forename: Xinqiang
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory for Agro-Biotechnology, College of Biological Science, China Agricultural University, Beijing, People's Republic of China.
authors.forename: Yizhi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Medical Molecular Virology of MOH and MOE, Fudan University Shanghai Medical College, Shanghai, People's Republic of China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, University of Illinois, Chicago, Illinois, USA.
authors.forename: Guoxing
authors.initials: G
authors.lastname: Zheng
authors.affiliation: Department of Microbiology and Immunology, College of Medicine, University of Illinois, Chicago, Illinois, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: He
authors.affiliation: State Key Laboratory for Agro-Biotechnology, College of Biological Science, China Agricultural University, Beijing, People's Republic of China Key Laboratory of Medical Molecular Virology of MOH and MOE, Fudan University Shanghai Medical College, Shanghai, People's Republic of China bwang3@fudan.edu.cn.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
mesh_terms: D000818:Animals; D051242:Caveolin 1 / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D018259:Herpesvirus 1, Human / Q000276:immunology*; D054884:Host-Pathogen Interactions; D007108:Immune Tolerance; D008168:Lung / Q000276:immunology*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D016019:Survival Analysis
chemical_list: D051242:Caveolin 1; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse