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Fulltext Syrian hamsters (Mesocricetus auratus) oronasally inoculated with a Nipah virus isolate from Bangladesh or Malaysia develop similar respiratory tract lesions

Baseler L, de Wit E, Scott DP, Munster VJ, Feldmann H

Vet Pathol, 2015 Jan;52(1):38-45.
PMID: 25352203 DOI: 10.1177/0300985814556189

Nipah virus is a paramyxovirus in the genus Henipavirus, which has caused outbreaks in humans in Malaysia, India, Singapore, and Bangladesh. Whereas the human cases in Malaysia were characterized mainly by neurological symptoms and a case fatality rate of ∼40%, cases in Bangladesh also exhibited respiratory disease and had a case fatality rate of ∼70%. Here, we compared the histopathologic changes in the respiratory tract of Syrian hamsters, a well-established small animal disease model for Nipah virus, inoculated oronasally with Nipah virus isolates from human cases in Malaysia and Bangladesh. The Nipah virus isolate from Bangladesh caused slightly more severe rhinitis and bronchointerstitial pneumonia 2 days after inoculation in Syrian hamsters. By day 4, differences in lesion severity could no longer be detected. Immunohistochemistry demonstrated Nipah virus antigen in the nasal cavity and pulmonary lesions; the amount of Nipah virus antigen present correlated with lesion severity. Immunohistochemistry indicated that both Nipah virus isolates exhibited endotheliotropism in small- and medium-caliber arteries and arterioles, but not in veins, in the lung. This correlated with the location of ephrin B2, the main receptor for Nipah virus, in the vasculature. In conclusion, Nipah virus isolates from outbreaks in Malaysia and Bangladesh caused a similar type and severity of respiratory tract lesions in Syrian hamsters, suggesting that the differences in human disease reported in the outbreaks in Malaysia and Bangladesh are unlikely to have been caused by intrinsic differences in these 2 virus isolates.
Fulltext Comparison of the pathogenicity of Nipah virus isolates from Bangladesh and Malaysia in the Syrian hamster

DeBuysscher BL, de Wit E, Munster VJ, Scott D, Feldmann H, Prescott J

PLoS Negl Trop Dis, 2013;7(1):e2024.
PMID: 23342177 DOI: 10.1371/journal.pntd.0002024

Nipah virus is a zoonotic pathogen that causes severe disease in humans. The mechanisms of pathogenesis are not well described. The first Nipah virus outbreak occurred in Malaysia, where human disease had a strong neurological component. Subsequent outbreaks have occurred in Bangladesh and India and transmission and disease processes in these outbreaks appear to be different from those of the Malaysian outbreak. Until this point, virtually all Nipah virus studies in vitro and in vivo, including vaccine and pathogenesis studies, have utilized a virus isolate from the original Malaysian outbreak (NiV-M). To investigate potential differences between NiV-M and a Nipah virus isolate from Bangladesh (NiV-B), we compared NiV-M and NiV-B infection in vitro and in vivo. In hamster kidney cells, NiV-M-infection resulted in extensive syncytia formation and cytopathic effects, whereas NiV-B-infection resulted in little to no morphological changes. In vivo, NiV-M-infected Syrian hamsters had accelerated virus replication, pathology and death when compared to NiV-B-infected animals. NiV-M infection also resulted in the activation of host immune response genes at an earlier time point. Pathogenicity was not only a result of direct effects of virus replication, but likely also had an immunopathogenic component. The differences observed between NiV-M and NiV-B pathogeneis in hamsters may relate to differences observed in human cases. Characterization of the hamster model for NiV-B infection allows for further research of the strain of Nipah virus responsible for the more recent outbreaks in humans. This model can be used to study NiV-B pathogenesis, transmission, and countermeasures that could be used to control outbreaks.
Fulltext Identifying Early Target Cells of Nipah Virus Infection in Syrian Hamsters

Baseler L, Scott DP, Saturday G, Horne E, Rosenke R, Thomas T, et al.

PLoS Negl Trop Dis, 2016 Nov;10(11):e0005120.
PMID: 27812087 DOI: 10.1371/journal.pntd.0005120

BACKGROUND: Nipah virus causes respiratory and neurologic disease with case fatality rates up to 100% in individual outbreaks. End stage lesions have been described in the respiratory and nervous systems, vasculature and often lymphoid organs in fatal human cases; however, the initial target organs of Nipah virus infection have not been identified. Here, we detected the initial target tissues and cells of Nipah virus and tracked virus dissemination during the early phase of infection in Syrian hamsters inoculated with a Nipah virus isolate from Malaysia (NiV-M) or Bangladesh (NiV-B).
METHODOLOGY/PRINCIPAL FINDINGS: Syrian hamsters were euthanized between 4 and 48 hours post intranasal inoculation and tissues were collected and analyzed for the presence of viral RNA, viral antigen and infectious virus. Virus replication was first detected at 8 hours post inoculation (hpi). Nipah virus initially targeted type I pneumocytes, bronchiolar respiratory epithelium and alveolar macrophages in the lung and respiratory and olfactory epithelium lining the nasal turbinates. By 16 hpi, virus disseminated to epithelial cells lining the larynx and trachea. Although the pattern of viral dissemination was similar for both virus isolates, the rate of spread was slower for NiV-B. Infectious virus was not detected in the nervous system or blood and widespread vascular infection and lesions within lymphoid organs were not observed, even at 48 hpi.
CONCLUSIONS/SIGNIFICANCE: Nipah virus initially targets the respiratory system. Virus replication in the brain and infection of blood vessels in non-respiratory tissues does not occur during the early phase of infection. However, virus replicates early in olfactory epithelium and may serve as the first step towards nervous system dissemination, suggesting that development of vaccines that block virus dissemination or treatments that can access the brain and spinal cord and directly inhibit virus replication may be necessary for preventing central nervous system pathology.
Fulltext Nipah@20: Lessons Learned from Another Virus with Pandemic Potential

Gómez Román R, Wang LF, Lee B, Halpin K, de Wit E, Broder CC, et al.

mSphere, 2020 07 08;5(4).
PMID: 32641430 DOI: 10.1128/mSphere.00602-20

Nipah disease is listed as one of the WHO priority diseases that pose the greatest public health risk due to their epidemic potential. More than 200 experts from around the world convened in Singapore last year to mark the 20th anniversary of the first Nipah virus outbreaks in Malaysia and Singapore. Most of these experts are now involved in responding to the coronavirus disease 2019 (COVID-19) pandemic. Here, members of the Organizing Committee of the 2019 Nipah Virus International Conference review highlights from the Nipah@20 Conference and reflect on key lessons learned from Nipah that could be applied to the understanding of the COVID-19 pandemic and to preparedness against future emerging infectious diseases (EIDs) of pandemic potential.
Fulltext Distinct VSV-based Nipah virus vaccines expressing either glycoprotein G or fusion protein F provide homologous and heterologous protection in a nonhuman primate model

de Wit E, Feldmann F, Cronin J, Goldin K, Mercado-Hernandez R, Williamson BN, et al.

EBioMedicine, 2023 Jan;87:104405.
PMID: 36508878 DOI: 10.1016/j.ebiom.2022.104405

BACKGROUND: Nipah virus (NiV) causes recurrent outbreaks of lethal respiratory and neurological disease in Southeast Asia. The World Health Organization considers the development of an effective vaccine against NiV a priority.
METHODS: We produced two NiV vaccine candidates using the licensed VSV-EBOV vaccine as a backbone and tested its efficacy against lethal homologous and heterologous NiV challenge with Nipah virus Bangladesh and Nipah virus Malaysia, respectively, in the African green monkey model.
FINDINGS: The VSV-EBOV vaccine expressing NiV glycoprotein G (VSV-NiVG) induced high neutralising antibody titers and afforded complete protection from homologous and heterologous challenge. The VSV-EBOV vaccine expressing NiV fusion protein F (VSV-NiVF) induced a lower humoral response and afforded complete homologous protection, but only partial heterologous protection. Both vaccines reduced virus shedding from the upper respiratory tract, and virus replication in the lungs and central nervous system. None of the protected animals vaccinated with VSV-NiVG or VSV-NiVF showed histological lesions in the CNS, but one VSV-NiVF-vaccinated animal that was not protected developed severe meningoencephalitis.
INTERPRETATION: The VSV-NiVG vaccine offers broad protection against NiV disease.
FUNDING: This study was supported by the Intramural Research Program, NIAID, NIH.