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Deep RNA sequencing reveal a complex transcriptional landscape of a bat adenovirus.

ABSTRACT: Bat adenoviruses are a group of recently identified adenoviruses (AdVs) which are highly prevalent in bats yet share low similarity to known AdVs from other species. In this study, deep RNA sequencing was used to analyze the transcriptome at five time points following the infection of a bat AdV in a kidney cell line derived from a myotis bat species. Evidence of AdV replication was observed with the proportion of viral RNAs ranging from 0.01% at 6 h to 1.3% at 18 h. Further analysis of viral temporal gene expression revealed three replication stages; the early stage genes encoding mainly for host interaction proteins, the intermediate stage genes for the DNA replication and assembly proteins, and the late stage genes for most structural proteins. Several bat AdV genes were expressed at stages that differed from their counterpart genes previously reported for human AdV. In addition, single-base resolution splice sites of several genes and promoter regions of all 30 viral genes were fully determined. Simultaneously, the temporal cellular gene expression profiles were identified. The most overrepresented functional categories of the differentially expressed genes were related to cellular immune response, transcription, translation, and DNA replication and repair. Taken together, the deep RNA sequencing provided a global, transcriptional profile of the novel BtAdV and the virus-host interactions, which will be useful for the understanding and investigation of AdV replication, pathogenesis and specific virus-bat interactions in future research.

ORGANISM(S): Myotis davidii

PROVIDER: GSE41275 | GEO | 2013/02/06

SECONDARY ACCESSION(S): PRJNA176424

REPOSITORIES: GEO

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Project description:Background: Coevolution between pathogens and their hosts decreases host morbidity and mortality. Bats can tolerate viruses which can be lethal to other vertebrate orders, including humans. Bat adaptations to infection include localized immune response, early pathogen sensing, high interferon expression without pathogen stimulation, and regulated inflammatory response. The immune reaction is costly, and bats suppress high-cost metabolism during torpor. In the temperate zone, bats hibernate in winter, utilizing a specific behavioural adaptation to survive detrimental environmental conditions and lack of energy resources. Hibernation torpor involves major physiological changes that pose an additional challenge to bat-pathogen coexistence. Here, we compared bat cellular reaction to viral challenge under conditions simulating hibernation, evaluating the changes between torpor and euthermia. Results: We infected the olfactory nerve-derived cell culture of Myotis myotis with an endemic bat pathogen, European bat lyssavirus 1 (EBLV-1). After infection, the bat cells were cultivated at two different temperatures – 37 ◦ C and 5 ◦ C - to examine the cell response during conditions simulating euthermia and torpor, respectively. The mRNA isolated from the cells was sequenced and analysed for differential gene expression attributable to the temperature and/or infection treatment. In conditions simulating euthermia, infected bat cells produce an excess signalling by multitude of pathways involved in apoptosis and immune regulation influencing proliferation of regulatory cell types which can, in synergy with other produced cytokines, contribute to viral tolerance. We found no up- or downregulated genes expressed in infected cells cultivated at conditions simulating torpor compared to non-infected cells cultivated under the same conditions. When studying the reaction of uninfected cells to the temperature treatment, bat cells show an increased production of heat shock proteins (HSPs) with chaperone activity, improving the bat’s ability to repair molecular structures damaged due to the stress related to the temperature change. Conclusions: The lack of bat cell reaction to infection in conditions simulating hibernation may contribute to the virus tolerance or persistence in bats. Together with the cell damage repair mechanisms induced in response to hibernation, the immune regulation may promote bats’ ability to act as reservoirs of zoonotic viruses such as lyssaviruses.

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Deep RNA sequencing reveal a complex transcriptional landscape of a bat adenovirus.

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