Henipavirus Encephalitis: Recent Developments and Advances

Abstract

The genus Henipavirus within the family Paramyxoviridae includes the Hendra virus (HeV) and Nipah virus (NiV) which were discovered in the 1990s in Australia and Malaysia, respectively, after emerging to cause severe and often fatal outbreaks in humans and animals. While HeV is confined to Australia, more recent NiV outbreaks have been reported in Bangladesh, India and the Philippines. The clinical manifestations of both henipaviruses in humans appear similar, with a predominance of an acute encephalitic syndrome. Likewise, the pathological features are similar and characterized by disseminated, multi-organ vasculopathy comprising endothelial infection/ulceration, vasculitis, vasculitis-induced thrombosis/occlusion, parenchymal ischemia/microinfarction, and parenchymal cell infection in the central nervous system (CNS), lung, kidney and other major organs. This unique dual pathogenetic mechanism of vasculitis-induced microinfarction and neuronal infection causes severe tissue damage in the CNS. Both viruses can also cause relapsing encephalitis months and years after the acute infection. Many animal models studied to date have largely confirmed the pathology of henipavirus infection, and provided the means to test new therapeutic agents and vaccines. As the bat is the natural host of henipaviruses and has worldwide distribution, spillover events into human populations are expected to occur in the future.

Keywords: Hendra virus; Nipah virus; encephalitis; pathological.

Figure 1

Diagrammatic representation of the henipavirus virion with an outer, plasma membrane‐derived envelop through which the viral G and F glycoproteins protrude. The matrix protein is found under the envelop. The central core consists of the nucleocapsid, viral RNA, phosphoprotein and polymerase.

Figure 2

Pathology of henipavirus infection: vasculopathy in Nipah virus encephalitis showing vasculitis, thrombosis (A) and endothelial multinucleated syncytia with viral inclusion (B, arrow). There are numerous Nipah viral inclusions/antigens within neurons (C), especially around necrotic plaques (D). Necrotic plaques may also have evidence of adjacent vascular thrombo‐occlusion (D, arrow). Vasculitis in Hendra encephalitis may manifest as mild endotheliitis (G). Hendra viral inclusions (H), antigens (F,I) and RNA (E) can be demonstrated in neurons. Viral antigens may also localize to the ependyma (F, arrow). Hematoxylin and eosin stain (A,B,D,G, H). Immunohistochemistry with new fuchsin (C) and DAB (F,I) chromogens, hematoxylin counterstain. In situ hybridization with NBT/BCIP substrate, and hematoxylin counterstain. Original magnification: ×40 (A–I). Permissions were obtained from reference 133 for A and B; reference 136 for C and D; reference 134 for E–I.