Association between nitric oxide synthesis and vaccination-acquired resistance to murine hepatitis virus by spf mice

Murine hepatitis virus strain 3 (MHV-3) produces a strain-dependent pattern of disease, with A/J and BALB/c mice being considered models of resistance and susceptibility, respectively. A role for nitric oxide in controlling infection remains debatable; thus, we monitored nitric oxide levels in blood and liver of immunized and nonimmunized spf mice during infection by electron paramagnetic resonance. In parallel, liver histology, virus titers, and plasma alanine aminotransferase (ALT) activity were monitored. Nitric oxide synthesis was barely detectable in BALB/c mice, which showed a progressive increase in virus titers and ALT activity. These animals died with a shorter survival time than A/J mice. The latter displayed a less severe infection and presented detectable levels of nitric oxide as nitrosyl complexes in blood and liver at 72 hpi. Immunized mice from both strains became resistant to MHV-3 and showed comparable levels of nitrosyl complexes in blood and liver at an early time (24 hpi). Thereafter, nitric oxide levels decreased but remained detectable in blood up to 96 hpi. Immunized mice were capable of clearing the virus and clearance was inhibited by administration of a nitric oxide synthase inhibitor. Overall, the results support a role for nitric oxide in controlling MHV-3 infection.