Transcriptome profiling of the virus-induced innate immune response in Pteropus vampyrus and its attenuation by Nipah virus interferon antagonist functions.

Glennon NB1, Jabado O2, Lo MK3, Shaw ML4.

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Abstract

Bats are important reservoirs for several viruses, many of which cause lethal infections in humans but have reduced pathogenicity in bats. As the innate immune response is critical for controlling viruses, the nature of this response in bats, and how it may differ from other mammals, is of great interest. Using next generation mRNAseq, we profiled the transcriptional response of Pteropus vampyrus bat kidney (PVK) cells to Newcastle disease virus (NDV), an avian paramyxovirus known to elicit a strong innate immune response in mammalian cells. This bat species is a known reservoir of Nipah virus (NiV) and Hendra virus (HeV). Analysis of the 200-300 regulated genes showed that interferon (IFN) and antiviral pathways are highly upregulated in NDV infected PVK cells, including genes such as IFN β, RIGI, MDA5, ISG15, and IRF1. NDV infected cells also upregulated several genes not previously characterized as antiviral such as RND1, SERTAD1, CHAC1, and MORC3. In fact, we show that MORC3 is induced by both IFN and NDV infection in PVK cells, but by neither stimulus in human A549 cells. In contrast to NDV, HeV and NiV infection of PVK cells failed to induce these innate immune genes. Likewise, an attenuated response was observed in PVK cells infected with recombinant NDVs expressing the NiV IFN antagonist proteins V and W. This study provides the first global profile of a robust virus-induced innate immune response in bats and indicates that henipavirus IFN antagonist mechanisms are likely active in bat cells.

IMPORTANCE:

Bats are the reservoir host for many highly pathogenic human viruses, including henipaviruses, lyssaviruses, SARS coronavirus, and filoviruses, and many other viruses have also been isolated from bats. Viral infections are reportedly asymptomatic or heavily attenuated in bat populations. Despite their ecological importance to viral maintenance, research into their immune system and mechanisms for viral control has only recently begun. Nipah virus and Hendra virus are two paramyxoviruses associated with high mortality rates in humans and whose reservoir is the Pteropus genus of bats. Greater knowledge of the innate immune response of P. vampyrus to viral infection may elucidate how bats serve as a reservoir for so many viruses.