Pathology of acute henipavirus infection in humans and animals

Abstract

Zoonoses as causes of human infections have been increasingly reported, and many of these are viruses that cause central nervous system infections. This paper focuses on the henipaviruses (family Paramyxoviridae, genus henipavirus) that have recently emerged to cause severe encephalitis and systemic infection in humans and animals in the Asia-Pacific region. The pathological features in the human infections comprise vasculopathy (vasculitis, endothelial multinucleated syncytia, thrombosis, etc.) and parenchymal cell infection in the central nervous system, lung, kidney, and other major organs. Most animals naturally or experimentally infected show more or less similar features confirming the dual pathogenetic mechanism of vasculopathy-associated microinfarction and direct extravascular parenchymal cell infection as causes of tissue injury. The most promising animal models include the hamster, ferret, squirrel monkey, and African green monkey. With increasing evidence of infection in the natural hosts, the pteropid bats and, hence, probable future outbreaks in many more countries, a greater awareness of henipavirus infection in both humans and animals is imperative.

Figure 1

Pathology of human and hamster henipavirus infection. (a) Vasculitis and associated intravascular thrombosis in human brain. (b) In an uninflamed meningeal vessel, a multinucleated giant cell (arrow) with viral inclusion arises from the endothelial surface. (c) Neuronal viral antigens in human Nipah infection. (d) Neuronal viral RNA in human Hendra infection. (e) Glomerulus in human Nipah infection with thrombosis, necrosis, and peripheral multinucleated giant cell formation (arrowhead). (f) Mild vasculitis (arrows) and encephalitis in Nipah-infected hamster brain. (g) Viral inclusions in neurons (arrowheads) and the rare neuronal syncytia (arrow) in Nipah-infected hamster brain. (h) Nipah viral antigens in neurons and ependymal cells in infected hamster. (h and e) stains (a, b, e, f, g), immunoperoxidase stains (c, h), in situ hybridisation (d). Magnification, objective ×20 (a, c, f, h), ×40 (b, d, e, g).

Figure 2

Pathology of dog and pig henipavirus infection. (a) Pulmonary vasculitis (arrow) and oedema in the Nipah-infected dog lung. (b) Glomerular (arrow) and tubular necrosis in the dog kidney. (c) Nipah viral RNA in dog glomerulus (arrow). Intra-alveolar multinucleated giant cell containing Nipah viral inclusions (d) (arrow) and viral RNA (e) (arrow). Bronchiolar syncytia (f) (arrow), viral antigens (g) (arrow) and RNA (h) (arrow) in Nipah-infected pig lung. Endothelial giant cell in pig pulmonary vessel (i) (arrows). (h and e) stains (a, b, d, f), immunoperoxidase stains (g, i), in situ hybridisation (c, e, h). Magnification, objective ×4 (a), ×10 (b), ×20 (c), ×40 (d-i).