Role of Host Staufen-Mediated Decay Mechanism in Enterovirus 71 Infection Cycle

RNA viruses, including Enterovirus 71 (EV71), depend entirely on the host proteins to perform numerous functions during the viral replication. Some RNA-binding proteins have been identified and reported that affect the recruitment of viral RNA for its replication purpose. Staufen protein is a member of the family of double-stranded RNA-binding protein, which involves in the transport or decay of mRNAs, or the assembly of stress granules (SGs) in mammalian cells. It is known that host RNA-binding proteins affect the stability of viral RNA genome, in such, escaping the viral RNA from cellular RNA degradation pathways. Staufen proteins, like other host RNA-binding proteins, seem to exhibit specialized functions as well as participate in multiple events during viral infection. Hence, we hypothesize that EV71 co-opts host staufen proteins to trigger the “Staufen-mediated decay” machine to perform diverse functions during viral replication and leads to effect on the pathogenesis outcome. A deeper understanding of the functions of the staufen family of proteins subverted for viral RNA replication will allow us to develop the novel antiviral strategies and provide new insights into host RNA biology. We propose the following aims: Aim 1 is to comprehensively identify the staufen-interacted cellular proteins (staufen-associated interactome), viral proteins and viral RNAs so as to trigger host staufen-mediated mRNA decay during the viral infection cycle. Aim 2: we want to define how human staufen proteins affect viral RNA metabolism via (i) 3’UTR, and (ii) the convergent changes in human mRNAs versus viral RNAs. Aim 3: we set out to delineate, via biochemical, gene expression, and cell-based analyses, the mode of action taken by host staufen proteins, such as Stau2 protein cripples host immune response and the impacts of viral/host mRNA quality control machinery, which is driven by staufen and staufen-associated proteins during EV71 infection cycle.

Project ID:PC10408-1512
External Project ID:MOST104-2320-B182-028