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Open Access Highly Accessed Research

Subclinical infection without encephalitis in mice following intranasal exposure to Nipah virus-Malaysia and Nipah virus-Bangladesh

Johanna Dups1, Deborah Middleton1, Fenella Long1, Rachel Arkinstall1, Glenn A Marsh1* and Lin-Fa Wang12

Author Affiliations

1 CSIRO Animal, Food and Health Science, Australian Animal Health Laboratory, Geelong, VIC 3219, Australia

2 Duke-NUS Graduate Medical School, 21 Lower Kent Ridge Road, Singapore 119077, Singapore

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Virology Journal 2014, 11:102  doi:10.1186/1743-422X-11-102

Published: 2 June 2014

Abstract

Background

Nipah virus and Hendra virus are closely related and following natural or experimental exposure induce similar clinical disease. In humans, encephalitis is the most serious outcome of infection and, hitherto, research into the pathogenesis of henipavirus encephalitis has been limited by the lack of a suitable model. Recently we reported a wild-type mouse model of Hendra virus (HeV) encephalitis that should facilitate detailed investigations of its neuropathogenesis, including mechanisms of disease recrudescence. In this study we investigated the possibility of developing a similar model of Nipah virus encephalitis.

Findings

Aged and young adult wild type mice did not develop clinical disease including encephalitis following intranasal exposure to either the Malaysia (NiV-MY) or Bangladesh (NiV-BD) strains of Nipah virus. However viral RNA was detected in lung tissue of mice at euthanasia (21 days following exposure) accompanied by a non-neutralizing antibody response. In a subsequent time course trial this viral RNA was shown to be reflective of an earlier self-limiting and subclinical lower respiratory tract infection through successful virus re-isolation and antigen detection in lung. There was no evidence for viremia or infection of other organs, including brain.

Conclusions

Mice develop a subclinical self-limiting lower respiratory tract infection but not encephalitis following intranasal exposure to NiV-BD or NiV-MY. These results contrast with those reported for HeV under similar exposure conditions in mice, demonstrating a significant biological difference in host clinical response to exposure with these viruses. This finding provides a new platform from which to explore the viral and/or host factors that determine the neuroinvasive ability of henipaviruses.

Keywords:
Henipavirus; Hendra virus; Nipah virus; Encephalitis; Mouse; Mice; Model