Abstract
Syrian hamsters (Mesocricetus auratus) are a pathogenesis model for the Nipah virus (NiV), and we sought to determine if they are also susceptible to the Cedar virus (CedPV). Following intranasal inoculation with CedPV, virus replication occurred in the lungs and spleens of infected hamsters, a neutralizing antibody was produced in some hamsters within 8 days post-challenge, and no conspicuous signs of disease occurred. CedPV replicated to a similar magnitude as NiV-Bangladesh in type I IFN-deficient BHK-21 Syrian hamster fibroblasts but replicated 4 logs lower in type I IFN-competent primary Syrian hamster and human pulmonary endothelial cells, a principal target of henipaviruses. The coinfection of these cells with CedPV and NiV failed to rescue CedPV titers and did not diminish NiV titers, suggesting the replication machinery is virus-specific. Type I IFN response transcripts Ifna7, Ddx58, Stat1, Stat2, Ccl5, Cxcl10, Isg20, Irf7, and Iigp1 were all significantly elevated in CedPV-infected hamster endothelial cells, whereas Ifna7 and Iigp1 expression were significantly repressed during NiV infection. These results are consistent with the hypothesis that CedPV’s inability to counter the host type I IFN response may, in part, contribute to its lack of pathogenicity. Because NiV causes a fatal disease in Syrian hamsters with similarities to human disease, this model will provide valuable information about the pathogenic mechanisms of henipaviruses.
Highlights
Henipaviruses are negative stranded viruses that belong to the Paramyxoviridae family and are hosted by several species of pteropid fruit bats [1,2]
Field studies subsequently identified that other species of pteropus bats were reservoir hosts of Nipah virus (NiV) [6]
Because of the number of immunological reagents and the available annotated genome for Syrian hamsters, which are model organisms that recapitulate many aspects of human disease caused by Previous work showed that, unlike NiV, CedPV fails to cause disease in ferrets or guinea pigs [7]
Summary
Henipaviruses are negative stranded viruses that belong to the Paramyxoviridae family and are hosted by several species of pteropid fruit bats [1,2]. HeV was identified and isolated in the 1990s after the severe disease in horses and equine workers, and subsequent work identified pteropus bats (Pteropus alecto and P. conspicillatus) as reservoir hosts of the virus [5]. Viruses 2019, 11, 291 first identified in Malaysia during an outbreak of severe disease amongst abattoir workers that had contracted the virus from swine. Field studies subsequently identified that other species of pteropus bats were reservoir hosts of NiV [6]. Since the discovery of these viruses, henipavirus sequences have been detected in many pteropid fruit bat species in Australia, Asia, and Africa, posing a significant risk to humans and livestock
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