Abstract
Dengue viruses 1–4 (DENV1-4) rely heavily on the host cell machinery to complete their life cycle, while at the same time evade the host response that could restrict their replication efficiency. These requirements may account for much of the broad gene-level changes to the host transcriptome upon DENV infection. However, host gene function is also regulated through transcriptional start site (TSS) selection and post-transcriptional modification to the RNA that give rise to multiple gene isoforms. The roles these processes play in the host response to dengue infection have not been explored. In the present study, we utilized RNA sequencing (RNAseq) to identify novel transcript variations in response to infection with both a pathogenic strain of DENV1 and its attenuated derivative. RNAseq provides the information necessary to distinguish the various isoforms produced from a single gene and their splice variants. Our data indicate that there is an extensive amount of previously uncharacterized TSS and post-transcriptional modifications to host RNA over a wide range of pathways and host functions in response to DENV infection. Many of the differentially expressed genes identified in this study have previously been shown to be required for flavivirus propagation and/or interact with DENV gene products. We also show here that the human transcriptome response to an infection by wild-type DENV or its attenuated derivative differs significantly. This differential response to wild-type and attenuated DENV infection suggests that alternative processing events may be part of a previously uncharacterized innate immune response to viral infection that is in large part evaded by wild-type DENV.
Highlights
Dengue viruses 1–4 (DENV1-4) are the world’s most prevalent arthropod-borne viruses [1]
While previous studies have described the changes in total gene expression with dengue virus infection, they have not been able to provide any information on the subtle variations of the host RNA
These variations lead to the production of gene isoforms that can have a profound effect on gene function
Summary
Dengue viruses 1–4 (DENV1-4) are the world’s most prevalent arthropod-borne viruses [1]. These viruses must effectively evade or suppress the host responses that act to restrict their replication [9,10,11]. Uncharacterized is whether the transcriptional start site (TSS) and post-transcriptional variations of host RNA, leading to the production of different gene isoforms, may play a role in DENV infection. In order to interrogate TSS and post-transcriptional RNA variations across the entire genome in response to DENV infection, we harnessed the power of RNA sequencing (RNAseq). RNAseq is a recently developed approach to transcriptome profiling that permits a precise quantification of RNA levels and their alternatively processed variants by means of high throughput, massively parallel sequencing and subsequent mapping of the resultant short sequence fragments onto a reference genome [32,33]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
