Antibody-dependent enhancement of Murray Valley encephalitis virus virulence in mice.

Enhancement of flavivirus infection in vitro in the presence of subneutralizing concentrations of homologous or heterologous antiserum has been well described. However, the importance of this phenomenon in the enhancement of flavivirus infection in vivo has not been established. In order to study antibody-mediated enhancement of flavivirus infection in vivo, we investigated the effect of passive immunization of mice with Japanese encephalitis virus (JE) antiserum on the outcome of infection with Murray Valley encephalitis virus (MVE). We show that prior treatment of mice with subneutralizing concentrations of heterologous JE antiserum resulted in an increase in viraemia titres and in mortality following challenge with wild-type MVE. Our findings support the hypothesis that subneutralizing concentrations of antibody may enhance flavivirus infection and virulence in vivo. These findings are of potential importance for the design of JE vaccination programs in geographic areas in which MVE co-circulates. Should subneutralizing concentrations of antibody remain in the population following JE vaccination, it is possible that enhanced disease may be observed during MVE epidemics.

Morphological features of Murray Valley encephalitis virus infection in the central nervous system of Swiss mice.

We have examined the histological and ultrastructural features of CNS infection with Murray Valley encephalitis (MVE) virus in mice inoculated with a virulent parental strain (BH3479). Light microscopic examination revealed neuronal necrosis in the olfactory bulb and hippocampus of MVE-infected brains by 5 days post-infection (pi). Electron microscopy of these regions showed endoplasmic reticulum membrane proliferation, and tubular and spherical structures in the cisternae of the endoplasmic reticulum, Golgi complex and nuclear envelope. At seven to eight days pi, infected neurones exhibited chromatin condensation and extrusion, nuclear fragmentation, loss of segments of the nuclear envelope, reduced surface contact with adjacent cells and loss of cytoplasmic organelles. This cell injury was particularly noticeable in the proximal CA3 and distal CA1 regions of the hippocampus. The inflammatory cell profile consisted of macrophages, lymphocytes and especially neutrophils, and many of these inflammatory cells were apoptotic. High mortality rates in the BH3479-infected population of mice correlated with the intense polymorphonuclear and mononuclear leucocyte inflammatory infiltrate in the CNS.

C-reactive protein in CNS infection.

Serum and CSF levels of CRP were measured by radial immunoassay in 99 subjects consisting of 20 controls, 34 pyogenic meningitis (PM), 21 tuberculous meningitis (TBM) and 24 viral encephalitis (VE). There was significant difference in the CRP levels (p less than 0.01) depending on the type of disease in both serum and CSF. The initial serum and CSF levels of CRP in patients with TBM was intermediate between those of PM and VE and were found to be significantly (p less than 0.001) low when compared with three days post treatment levels in children with PM. Both serum and CSF-CRP levels were significantly high (p less than 0.001) in patients succumbing to death than those who survived. Measurement of CRP in serum and CSF is a useful parameter in differentiating partially treated PM from TBM.

Effect of anti-mu-chain-specific immunosuppression on Chikungunya virus encephalitis of mice.

Mice neonatally immunosuppressed with anti-mu antiserum failed to produce circulating antibodies to sheep erythrocytes and showed a marked decrease in circulating immunoglobulins. However, when they were intracerebrally infected with Chikungunya virus (a group A togavirus), they showed a mortality rate consistently lower than non-immunosuppressed control mice. Several possible explanations for this finding are discussed.