Dynamin2 S-nitrosylation regulates adenovirus type 5 infection of epithelial cells.
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 S-nitrosylation modifications. In this study, we demonstrate a role for dynamin2 S-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 S-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 S-nitrosylation of dynamin2 and eNOS: there is a rapid decrease in eNOS S-nitrosylation and a concomitant increase in the dynamin2 S-nitrosylation. These results support the hypothesis that dynamin2 S-nitrosylation following eNOS activation facilitates adenovirus infection of host epithelial cells.
Department of Urology and Prostate Disease Center, University of Florida, Gainesville, FL 32610, USA.
Zhimin
Z
Wang
Department of Urology and Prostate Disease Center, University of Florida, Gainesville, FL 32610, USA.
Jae Il
JI
Kim
Department of Pathology, Georgia Health Sciences University, Augusta, GA 30912, USA.
Nicole
N
Frilot
Department of Anatomy and Cell Biology, University of Florida, Gainesville, FL 32610, USA.|Department of Urology and Prostate Disease Center, University of Florida, Gainesville, FL 32610, USA.
Yehia
Y
Daaka
D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D000257:Adenoviridae Infections / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000821:virology; D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D003545:Cysteine / Q000235:genetics / Q000378:metabolism; D034285:Dynamin II / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000201:enzymology / Q000378:metabolism / Q000821:virology*; D055785:Gene Knockdown Techniques; D006801:Humans; D009154:Mutation; D009569:Nitric Oxide / Q000235:genetics / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism
D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D051057:Proto-Oncogene Proteins c-akt; D034285:Dynamin II; D003545:Cysteine