Nitric oxide-induced nitrative stress involved in microbial pathogenesis

The pathogenic mechanism of infections is a complicated but important scientific theme that is now attracting great attention because of its association with host-derived as well as microbial factors. Recent advances in free radical research revealed that reactive oxygen and nitrogen oxide species such as superoxide (O₂^-) and nitric oxide (NO) play a leading role in the pathogenesis of infections caused by viral pathogens including influenza virus and other RNA viruses. Although NO and O ₂^- have antimicrobial activity against bacteria, fungi, and parasites, in some viral infections they have an opposite effect. This exacerbation caused by NO and O₂^- is mediated by reactive nitrogen oxides, for example, peroxynitrite (ONOO^-), generated by reaction of NO with O₂^-. These nitrogen oxides have strong oxidation and nitration potential and can modify biological molecules, thereby creating oxidative and nitrative stress that contributes to pathogenic processes during viral infection. Nitrative stress-mediated 8-nitroguanosine formation during influenza or Sendai virus infection has been the focus of enormous interest because it involves unique biochemical and pharmacological properties such as redox activity and mutagenic potential. In this review, we discuss the nature and impact of nitrative stress in viral infection, with emphasis on nitrative stress-mediated viral pathogenesis, which we have recently been investigating.