Comprehensive Analysis of Rotavirus-Induced Transcriptomic Alterations

Rotavirus (RV) infection of MA104 cells induced many changes in gene expression, as determined by deep sequencing of mRNAs and lncRNAs from infected versus uninfected cells. 24 hours p.i. 3,651 mRNAs and 4,655 lncRNAs were found significantly up- or down-regulated. Since rotavirus is found worldwide and is a major cause of severe gastrointestinal disease, primarily of young children, these data provide a glimpse into the genomic changes induced by the virus and may serve as the basis for further studies into its molecular pathogenesis.

Why It Matters

Rotavirus is the most common cause of severe diarrhoea-associated dehydration worldwide, infecting millions of children every year. Understanding the host transcriptional changes elicited by the pathogen can provide key insights in how the virus manipulates host cell processes to enable its own survival. For patients, knowing these host changes can inform clinicians and health care providers of a patient’s prognosis for recovery from the infection. In this study, we identify and map the ‘unmapped’ lncRNA transcriptional landscape, which is fundamentally reorganised by rotavirus infection to modulate host gene expression to sustain infection.

Advancing knowledge in transcriptomics

Expression of the genome as RNA provides the clinician with insight into the pathogen’s biology. In this study, expression of the genome of RV, a major human cold virus, was found to significantly activate innate immunity responses important to pathogen defense. In addition, many essential metabolic pathways important to normal cell function were significantly decreased in expression, implying that the energy from these pathways is diverted to replication of the virus or to a general host defense.

The various classes of RNA expression highlighted in this issue of Future Virology provide insights into disease progression of ARD that should be useful to healthcare professionals managing individual cases. Experimental validation of immune-related mRNAs showed that a number of mRNAs, including OASL and C3, were upregulated in individuals with severe infection and were detectable at both mRNA and protein levels, and therefore provide reliable biomarkers that allow stratification of disease severity. In addition, a large number of novel lncRNAs have been identified, including lncRNA-6479 and lncRNA-4290, which can be considered as targets for vaccines and therapeutic approaches to prevent severe disease and improve patient management.

Integrated transcriptome analyses revealed insights relevant for future revisions of management guidelines and public health policies for childhood vaccination and rotavirus disease, especially severe cases. These insights will be useful for predicting and controlling future outbreaks and for improving current vaccines as well as future long-term strategies for rotavirus management.

Deep Diving into the Molecular Landscape

The massive transcriptomic changes induced by Chilo iridescent virus infection included more than 8,000+ unique transcripts which were up-regulated or down-regulated. These host gene expression changes can be broadly categorized into two domains.