Peroxynitrite inhibition of Coxsackievirus infection by prevention of viral RNA entry.
Although peroxynitrite is harmful to the host, the beneficial effects of peroxynitrite are less well understood. We explored the role of peroxynitrite in the host immune response to Coxsackievirus infection. Peroxynitrite inhibits viral replication in vitro, in part by inhibiting viral RNA entry into the host cell. Nitrotyrosine, a marker for peroxynitrite production, is colocalized with viral antigens in the hearts of infected mice but not control mice. Nitrotyrosine coprecipitates with the viral polypeptide VP1 as well. Guanidinoethyl disulfide, a scavenger of peroxynitrite, blocks peroxynitrite inhibition of viral replication in vitro and permits an increase in viral replication in vivo. These data suggest that peroxynitrite is an endogenous effector of the immune response to viruses.
Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Elizaveta
E
Padalko
Tomokazu
T
Ohnishi
Kenji
K
Matsushita
Henry
H
Sun
Karen
K
Fox-Talbot
Clare
C
Bao
William M
WM
Baldwin
Charles J
CJ
Lowenstein
D000818:Animals; D003384:Coxsackievirus Infections / Q000276:immunology / Q000517:prevention & control*; D029822:Enterovirus B, Human / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D007109:Immunity; D051379:Mice; D008809:Mice, Inbred C3H; D030421:Peroxynitrous Acid / Q000276:immunology / Q000494:pharmacology*; D012367:RNA, Viral / Q000187:drug effects* / Q000493:pharmacokinetics; D014162:Transfection; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000032:analysis; D015678:Viral Structural Proteins; D014779:Virus Replication / Q000187:drug effects
D012367:RNA, Viral; D015678:Viral Structural Proteins; D030421:Peroxynitrous Acid; C002744:3-nitrotyrosine; D014443:Tyrosine