Henipavirus Immune Evasion and Pathogenesis Mechanisms: Lessons Learnt from Natural Infection and Animal Models

Abstract

Nipah henipavirus (NiV) and Hendra henipavirus (HeV) are zoonotic emerging paramyxoviruses causing severe disease outbreaks in humans and livestock, mostly in Australia, India, Malaysia, Singapore and Bangladesh. Both are bat-borne viruses and in humans, their mortality rates can reach 60% in the case of HeV and 92% for NiV, thus being two of the deadliest viruses known for humans. Several factors, including a large cellular tropism and a wide zoonotic potential, con-tribute to their high pathogenicity. This review provides an overview of HeV and NiV pathogenicity mechanisms and provides a summary of their interactions with the immune systems of their different host species, including their natural hosts bats, spillover-hosts pigs, horses, and humans, as well as in experimental animal models. A better understanding of the interactions between henipaviruses and their hosts could facilitate the development of new therapeutic strategies and vaccine measures against these re-emerging viruses.

Host–Pathogen Interactions Influencing Zoonotic Spillover Potential and Transmission in Humans

“…From this perspective, it is interesting to compare MeV and RSV and the highly pathogenic, re-emerging NiV, for which transmissibility among humans appears to be much less efficient. NiV is a highly pathogenic member of the genus Henipavirus within the family Paramyxoviridae that first emerged from fruit bats in Malaysia and Singapore in 1999 during an outbreak of severe respiratory disease in pigs and fatal encephalitis in humans [ 30 , 32 , 60 , 61 ]. Since 2001, smaller outbreaks of NiV infections in India and Bangladesh have regularly occurred, with reports of human-to-human transmission being an important hallmark in many of these later outbreaks [ 11 , 62 , 63 , 64 ].…”

“…All three of the viral infections caused by MeV, NiV and RSV are thought to originate in the airways after infection through the oronasopharyngeal route. From here, both MeV and NiV are able to spread from their initial infection of immune cells to associated lymphoid organs and the bloodstream before establishing systemic infection of other tissues, including the submucosa, tongue, buccal mucosa, trachea, nose and skin for MeV and endothelial cells in many organs for NiV, including notably the lung, kidneys and the central nervous system (CNS) [ 32 , 71 ]. MeV initially infects antigen-presenting cells (APCs) in the respiratory tract, which will then transmit the infection to activated lymphocytes, thus disseminating the virus in cis in blood circulation and then by contact with lung epithelial cells in the respiratory tract for the shedding of the virus [ 72 , 73 ].…”

“…Studies of NiV infection in a hamster model showed that the respiratory epithelium is the initial area for NiV replication in endothelial cells that then leads to viraemia and the systemic spread of infection [ 83 , 84 ]. Immunohistological data of in vivo infection demonstrate that NiV infects epithelial cells at mucosal surfaces, including the respiratory tract, the kidneys and the bladder, consistent with viral shedding in airway secretions and urine [ 32 , 85 , 86 ]. In human cases of NiV infection, respiratory symptoms may vary but many reports have suggested an important role of respiratory secretions in human-to-human transmission of NiV [ 87 ].…”

“…Of note, two licensed vaccines against EBOV are currently available for use in humans [ 28 , 29 ]. Whereas EBOV spread seems more restricted to primates including humans, NiV (and numerous other Henipaviruses) shows one of the broadest ranges of susceptible hosts to infection [ 30 , 31 , 32 , 33 ]. Both viruses have recently been placed in the WHO blueprint list of pathogens for which research and development of countermeasures should be prioritized in the face of their suspected high-risk pandemic potential [ 34 ].…”

‘Langya’ Virus, A Zoonotic Henipavirus Recently Emerged in China, Public Health Concerns, and Counteracting Prevention and Control Measures- An Update

“…LayV is an enveloped virus and has a single-stranded RNA genome with a negative orientation as in other viruses of the genus Henipavirus in the family Paramyxoviridae [18,19]. This genome codes for six structural proteins (3' end to 5' end): nucleocapsid (N), phosphoprotein (P), matrix protein (M), surface glycoprotein (G), fusion protein (F), and large viral RNA-dependent RNA polymerase (L) [20]. This new virus appears to be a close relative of two prominent human viruses: Nipah virus and Hendra virus.…”