Abstract
Bats are natural reservoirs for a spectrum of infectious zoonotic diseases including the recently emerged henipaviruses (Hendra and Nipah viruses). Henipaviruses have been observed both naturally and experimentally to cause serious and often fatal disease in many different mammal species, including humans. Interestingly, infection of the flying fox with henipaviruses occurs in the absence of clinical disease. The extreme variation in the disease pattern between humans and bats has led to an investigation into the effects of henipavirus infection on the innate immune response in bat cell lines. We report that henipavirus infection does not result in the induction of interferon expression, and the viruses also inhibit interferon signaling. We also confirm that the interferon production and signaling block in bat cells is not due to differing viral protein expression levels between human and bat hosts. This information, in addition to the known lack of clinical signs in bats following henipavirus infection, suggests that bats control henipavirus infection by an as yet unidentified mechanism, not via the interferon response. This is the first report of henipavirus infection in bat cells specifically investigating aspects of the innate immune system.
Highlights
Bats have been identified as the natural reservoir hosts of many human and animal pathogens of medical importance, including a spectrum of infectious zoonotic agents such as Ebola virus [1], SARS coronavirus [2,3], Nipah virus [4,5] and Hendra virus [6]
Stimulation of bat cells with poly I:C results in the induction of type I (IFN-a and IFN-b) and type III interferons (IFN-l) [42,48,50], demonstrating that the interferon production pathways are functional in these cells
Transfection of 10 mg poly I:C was used as a positive control as previously reported [42]. Following infection both interferon alpha (IFN-a) and IFN-b mRNA transcripts were comparable to that observed in mock infected cells (Figure 1a). This suggests that the interferon production pathway is antagonized by each of the three tested henipaviruses, which is comparable to that seen in human cells [58]
Summary
Bats have been identified as the natural reservoir hosts of many human and animal pathogens of medical importance, including a spectrum of infectious zoonotic agents such as Ebola virus [1], SARS coronavirus [2,3], Nipah virus [4,5] and Hendra virus [6]. Bats harbour a large number of emerging pathogens, they rarely show any signs of disease [1,7,8,9,10,11]. An example of this is Hendra virus in Australian fruit bats; there is high seroprevalence in the absence of clinical signs suggesting that there is no disease in bats associated with this virus. The nature of persistent, non-clinical, infections and the mechanism of transmission of viruses between bats and from bat to humans and other mammals remains largely unknown. The ability of bats to harbour highly pathogenic viruses, in the absence of significant clinical disease or pathology is driving research into further understanding bat biology, immunology and ecology
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