Antiviral effect of nitric oxide during Japanese encephalitis virus infection

Abstract

The ability of Japanese encephalitis virus (JEV) and JEV-induced macrophage derived neutrophil chemotactic factor (MDF) to produce nitric oxide (NO), and the possible antiviral effect of NO during JEV infection, was investigated. Splenic macrophages of JEV infected mice produced maximum NO in vivo at day 7 post infection, and in vitro at 24 h after JEV stimulation. MDF-induced NO production was dose dependent and maximal at 60 min after MDF treatment. The response was sensitive to anti-MDF antibody treatment and the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA). Pretreatment of mice with L-NMMA increased the mortality to 100% in JEV infected mice in vivo and inhibited NO production in vitro, while MDF stimulated macrophages inhibited virus replication with high levels of NO production. MDF treatment increased the survival rate of JEV infected mice. The findings thus demonstrate that MDF induces production of NO during JEV infection, which has an antiviral effect. This may be one of the important mechanisms of natural immunity in controlling the initial stages of JEV infection.

Gamma Interferon Plays a Crucial Early Antiviral Role in Protection against West Nile Virus Infection

“…Increased MVEV burden was detected in the serum and spleen at day 4 after infection in IFN-␥ Ϫ/Ϫ mice, and brain titers at day 8 were indistinguishable from wild-type mice, results that are consistent with our findings. Interestingly, higher mortality after MVEV infection was also observed in mice deficient in inducible nitric oxide synthase-2, an effector molecule downstream of IFN-␥ that has been reported to affect outcome after infection with JEV (56,57) and other RNA viruses (14,40). Surprisingly, our virologic data suggest that IFN-␥ has a less significant antiviral role in the CNS.…”

Trend of Japanese encephalitis in North India: evidence from thirty-eight acute encephalitis cases and appraisal of niceties

“…In CSF the elevated level of cells and alteration of protein level indicates penetration of the blood-brain barrier. The migration of neutrophils at the site of injury may be attributed to the production of soluble macrophage-derived factor (MDF), which is one of the key mediators in the host-innate immune response during JEV infection [17]. The mild anaemia may be because a result of MDF-induced hyperferretimia in serum [18].…”

Immunobiology of Japanese Encephalitis Virus

“…An in vitro study has demonstrated the antiviral activity of IFN-against JEV (Hasegawa et al, 1990) and we have confirmed a critical role of IFN-in recovery from JEV infection using IFN--/-mice, which demonstrate significantly increased mortality relative to wild-type mice (Larena and Lobigs, unpublished). IFN-mediates its antiviral effect, at least in part, through induction of nitric oxide (NO) synthase (Karupiah et al, 1993) and an inhibitory effect of NO on JEV growth has been documented (Lin et al, 1997;Saxena et al, 2000). IFN-, derived from / T cells is necessary for the early control of dissemination of WNV, which is closely related to JEV (Wang et al, 2003a).…”