Role of nitric oxide in murine cytomegalovirus (MCMV) infection

  • Kazuo Tanaka
  • S. Noda
Keywords: cytomegalovirus, nitric oxide, inducible NO synthase (iNOS), iNOS-gene knock out mouse


Cytomegalovirus (CMV) is a typical pathogen of an opportunistic infection. In this review article, various roles of nitric oxide (NO) in murine CMV (MCMV) infections, including acute, persistent and latent infections, are discussed. In the acute phase of MCMV infection, NO plays a protective role against MCMV infection. In contrast, NO has been proven to act as a pathogenic factor in a model of MCMV pneumonitis. In MCMV persistent infection, when MCMV was detected only in the salivary gland, T cells of mice were modified to produce a massive amount of such cytokines as TNF-a and IFN-y upon in vivo stimulation with anti-CD3. These cytokines then induced mRNA for inducible NO synthase (iNOS), thus resulting in the production of a large amount of NO. A histochemical study demonstrated that NO damaged bronchial epithelial cells, and thereby apparently inducing pneumonitis. In the case of a latent infection, when viral DNA was detected in the host in spite of the absence of any infectious particle, NO increased the amount of persistently-infected MCMV-DNA. As a result, NO was found to act as "a double edged sword" in the CMV-host relationship.