Peroxynitrite inhibition of Coxsackievirus infection by prevention of viral RNA entry

doi:10.1073/pnas.0400518101

Peroxynitrite inhibition of Coxsackievirus infection by prevention of viral RNA entry

Departments of ^*Medicine and ^†Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205

Edited by Louis J. Ignarro, University of California School of Medicine, Los Angeles, CA, and approved June 24, 2004 (received for review January 22, 2004)

Abstract

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.

Footnotes

↵ ‡ To whom correspondence should be addressed at: 950 Ross Building, 720 Rutland Avenue, The Johns Hopkins University School of Medicine, Baltimore, MD 21205. E-mail: clowenst{at}jhmi.edu.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations: CVB3, Coxsackievirus serotype B3; NOS, NO synthase; GED, guanidinoethyl disulfide; NAME, nitroarginine methyl ester, MOI, multiplicity of infection; pfu, plaque-forming units.