Herpes Simplex Virus 1 Suppresses the Function of Lung Dendritic Cells via Caveolin-1

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. He...

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Bibliographic Details
Published in:Clinical and vaccine immunology 2015-08, Vol.22 (8), p.883-895
Main Authors: Wu, Bing, Geng, Shuang, Bi, Yanmin, Liu, Hu, Hu, Yanxin, Li, Xinqiang, Zhang, Yizhi, Zhou, Xiaoyu, Zheng, Guoxing, He, Bin, Wang, Bin
Format: Article
Language:English
Subjects:
Animals
Caveolin 1 - metabolism
Clinical Immunology
Dendritic Cells - immunology
Female
Herpes simplex virus 1
Herpesvirus
Herpesvirus 1, Human - immunology
Host-Pathogen Interactions
Immune Tolerance
Lung - immunology
Mice, Inbred C57BL
Mice, Knockout
Nitric Oxide - metabolism
Nitric Oxide Synthase Type II - metabolism
Survival Analysis
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Summary: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.
ISSN:1556-6811
1556-679X
1556-679X
DOI:10.1128/CVI.00170-15