Three newly recognized encephalitogenic zoonotic viruses spread from fruit bats of the genus Pteropus (order Chiroptera, suborder Megachiroptera) have been recognised over the past decade. These are: Hendra virus, formerly named equine morbillivirus, which was responsible for an outbreak of disease in horses and humans in Brisbane, Australia, in 1994; Australian bat lyssavirus, the cause of a severe acute encephalitis, in 1996; and Nipah virus, the cause of a major outbreak of encephalitis and pulmonary disease in domestic pigs and people in peninsula Malaysia in 1999. Hendra and Nipah viruses have been shown to be the first two members of a new genus, Henipavirus, in the family Paramyxoviridae, subfamily Paramyxovirinae, whereas Australian bat lyssavirus is closely related antigenically to classical rabies virus in the genus Lyssavirus, family Rhabdoviridae, although it can be distinguished on genetic grounds. Hendra and Nipah viruses have neurological and pneumonic tropisms. The first humans and equids with Hendra virus infections died from acute respiratory disease, whereas the second human patient died from an encephalitis. With Nipah virus, the predominant clinical syndrome in humans was encephalitic rather than respiratory, whereas in pigs, the infection was characterised by acute fever with respiratory involvement with or without neurological signs. Two human infections with Australian bat lyssavirus have been reported, the clinical signs of which were consistent with classical rabies infection and included a diffuse, non-suppurative encephalitis. Many important questions remain to be answered regarding modes of transmission, pathogenesis, and geographic range of these viruses.
Japanese encephalitis virus (JEV) and West Nile virus (WNV) provide some of the most important examples of emerging zoonotic viral encephalitides. For these flaviviruses, only a small proportion of those infected develop clinical features, and these may range from a non-specific flu-like illness to a severe fatal meningoencephalitis, often with Parkinsonian features, or a poliomyelitis-like flaccid paralysis. The factors governing the clinical presentations, and outcome of flavivirus infections are poorly understood, but studies have looked at viral virulence determinants and the host immune response. Previous studies on JEV have suggested that the distribution of the four genotypes across Asia may relate to the differing clinical epidemiology (epidemic disease in the north, endemic disease in the south). However, new data based on the complete nucleotide sequence of a virus representing one of the oldest lineages, and phylogenetic analyses of all JEV strains for which genetic data are available, suggest that the distribution is best explained in terms of the virus' origin in the Indonesia-Malaysia region (where all genotypes have been found), and the spread of the more recent genotypes to new geographical areas. Clinical studies have shown that innate immunity, as manifested by interferon alpha levels, is important in JEV and other flaviviruses, but treatment with interferon alpha did not improve the outcome. A failure of the humoral immune response, is associated with death from encephalitis caused by JEV and WNV. Cellular immunity has been less well characterized, but CD8+ and CD4+ T cells are thought to be important.