1887

Abstract

Dynamin2 is a large GTPase that regulates vesicle trafficking, and the GTPase activity of dynamin2 is required for the multistep process of adenovirus infection. Activity of dynamin2 may be regulated by post-translational phosphorylation and -nitrosylation modifications. In this study, we demonstrate a role for dynamin2 -nitrosylation in adenovirus infection of epithelial cells. We show that adenovirus serotype 5 (Ad5) infection augments production of nitric oxide (NO) in epithelial cells and causes the -nitrosylation of dynamin2, mainly on cysteine 86 (C86) and 607 (C607) residues. Forced overexpression of dynamin2 bearing C86A and/or C607A mutations decreases Ad5 infection. Diminishing NO synthesis by RNAi-induced knockdown of endogenous endothelial NO synthase (eNOS) expression attenuates virus infection of target cells. Ad5 infection promotes the kinetically dynamic -nitrosylation of dynamin2 and eNOS: there is a rapid decrease in eNOS -nitrosylation and a concomitant increase in the dynamin2 -nitrosylation. These results support the hypothesis that dynamin2 -nitrosylation following eNOS activation facilitates adenovirus infection of host epithelial cells.

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2012-10-01
2019-12-05
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