Grant: Master's Award: Canada Graduate Scholarships

Elucidating the Mechanisms Underlying the RSV-Induced Shift in Host Cell Translational Profiles Respiratory Syncytial Virus (RSV) is a pervasive infectious agent that acts as a leading cause of severe acute lower respiratory tract infection in infants. Viruses, such as RSV, are dependent on host cells for replication. In order to generate infectious viral particles, viruses hijack ribosomes, the cellular structures responsible for decoding genetic information contained in messenger RNA (mRNA) to direct protein synthesis. Using next-generation sequencing methods, researchers in our lab have observed altered ribosome decoding patterns in RSV-infected cells. Specifically, certain RSV genes are somehow preferentially recruited to cellular ribosomes, and RSV infection further biases which cellular mRNAs are converted to proteins, but the mechanism by which RSV introduces these changes to cellular protein production is not understood. RSV M2-1 is a viral protein known to promote viral replication by facilitating the expression of genes necessary for RSV particle synthesis. We hypothesize that M2-1 also promotes ribosome recruitment to certain RSV genes and causes the observed bias in cellular protein production. To test this hypothesis, the normal (or mutated) RSV M2-1 protein will be expressed in human cells by itself, in the absence of a whole RSV infection. These experiments will determine whether it is M2-1 that is key for this RSV-associated shift in gene expression. Given the degree to which RSV adversely affects the health of paediatric patients, coupled with the current deficit in medical interventions to limit RSV infection, investigations into the RSV life cycle are paramount, as these studies represent potential sources for life-saving therapeutics.