An Investigation of the Effect of Temperature on the Innate Immune Response to Aberrant Viral RNAs of Influenza A Virus

Abstract

Influenza A virus is the causative agent of several flu pandemics and yearly seasonal flu epidemics, causing morbidity and mortality in humans worldwide. The seasonality of flu epidemics has led virologists to hypothesize that influenza viruses are temperature sensitive. Studies have demonstrated that temperature indeed impacts viral RNA replication, RNA secondary structure, and host immune responses. However, the mechanisms by which temperature modulates viral replication and the innate immune response remain unclear. Using classic virology and molecular biology techniques, I here studied the interplay between temperature, the innate immune response during viral infection and RNA structures presents in aberrant viral RNAs known as mini viral RNAs (mvRNAs). These mvRNAs were previously shown to activate the innate immune response in an RNA structure-dependent manner. Specifically, I investigated how temperature modulates the host innate immune response in the presence of mvRNAs, in vitro. I find that the innate immune response was positively correlated with temperature. By clarifying how temperature, especially in the context of mvRNAs mediate the host immune response, my study contributes to a more complete mechanistic understanding of IAV infection at the molecular level.