Herpes Simplex Virus 1.pdf (4.13 MB)
Herpes Simplex Virus 1 Suppresses the Function of Lung Dendritic Cells via Caveolin-1.
journal contribution
posted on 2016-07-29, 00:00 authored by B. Wu, S. Geng, Y. Bi, H. Liu, X. Li, Y. Zhang, X. Zhou, G Zheng, B. He, B. WangCaveolin-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.
Funding
This work was supported in part by the National Science Foundation of China (31430027 and 30930068), MOST national 863 project of China (2012AA02A407), and the National Science and Technology Major Program of Infectious Diseases (2013ZX10002001) to Bin Wang
History
Publisher Statement
This is the copy of an article published in Clinical and Vaccine Immunology © 2013 American Society for Microbiology Publications.Publisher
American Society for Microbiologyissn
1556-6811Issue date
2015-08-01Usage metrics
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