Unknown,Transcriptomics,Genomics,Proteomics

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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. Deep RNA sequencing was used to analyze the transcriptome at five time points(0h,6h,8h, 12h 18h) following the infection of a bat AdV in a bat kidney cell.

ORGANISM(S): Myotis davidii

SUBMITTER: Lijun Wu

PROVIDER: E-GEOD-41275 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

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

Wu Lijun L Zhou Peng P Ge Xingyi X Wang Lin-Fa LF Baker Michelle L ML Shi Zhengli Z

Journal of virology 20121024 1

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 tem ...[more]

PMID: 23097437

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Project description:Viral infections are associated with extensive remodeling of the cellular proteome. Viruses encode gene products that manipulate host proteins to redirect cellular processes or subvert antiviral immune responses. One way in which host antiviral proteins antagonize viral infection is by associating with viral genomes and inhibiting essential viral processes. Adenovirus (AdV) encodes gene products from the early E4 region which are necessary for productive infection. Some cellular antiviral proteins are known to be targeted by AdV E4 gene products, resulting in their degradation or mislocalization. However, the full repertoire of host proteins manipulated by viral E4 proteins has not been defined. To identify cellular proteins and processes manipulated by viral products, we developed a global, un-biased proteomics approach to analyze changes to the host proteome during infection with Adenovirus serotype 5 (Ad5) virus. We combined quantification of total protein abundance in the proteome together with an analysis of proteins associated with viral genomes using isolation of Proteins on Nascent DNA (iPOND). By Integrating these proteomics datasets, we identified cellular factors that are degraded in an E4-dependent manner or are associated with the viral genome in the absence of E4 proteins. We further show that some identified proteins exert inhibitory effects on Ad5 infection. Our systems-level analysis reveals cellular processes that are manipulated during Ad5 infection and points to host factors counteracted by early viral proteins as they remodel the host proteome to promote efficient infection. Importance Viral infections stimulate myriad changes to the host cell proteome. As viruses harness cellular processes and counteract host defenses, they impact abundance, modifications, or localization of cellular proteins. Elucidating the dynamic changes to the cellular proteome during viral replication is integral to understanding how virus-host interactions influence the outcome of infection. Adenovirus serotype 5 (Ad5) encodes early gene products from the E4 genomic region that are known to alter host response pathways and promote replication, but the full extent of proteome modifications they mediate is not known. We use an integrated proteomics approach to quantitate protein abundance and protein associations with viral DNA during virus infection. Systems-level analysis identifies cellular proteins and processes impacted in an E4-dependent manner that could overcome potentially inhibitory host defenses. This study provides a global view of Adenovirus-mediated proteome remodeling which can serve as a model to investigate virus-host interactions of DNA viruses.

Dataset Information

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

Publications

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

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