The cytosolic pattern recognition receptor, retinoic-acid inducible gene I (RIG-I), plays a key signaling role in initiating the type-1 interferon (IFN1) host response in the presence of a virus. RIG-I senses viral RNA in the host cell and activates a signaling cascade that leads to the production of IFN1. The function of RIG-I has been frequently studied during an infection with an RNA virus, however studies of RIG-I with DNA viruses are not as abundant. Adenovirus is a nonenveloped, double-stranded DNA virus containing early proteins that function to create a more advantageous host-cell environment for viral replication. Adenovirus early region 4 11 kilodalton protein (E4 11k) is known to relocalize host-cell target proteins with functions ranging from double-strand break repair to mRNA regulation. One structure that is targeted for relocalization is the P body, which is involved in cytoplasmic RNA regulation and mRNA degradation. One major P body protein that E4 11k interacts with is DEAD-Box Helicase 6 (Ddx6), that acts as an RNA helicase and has functions in mRNA decapping. More recently, Ddx6 has been found to bind to RIG-I and is known to have both antiviral and pro-viral roles during infection. It is important to note that adenovirus infection has been shown to induce IFN-ß in a biphasic manner, with the late phase being RIG-I dependent. This project aims to look at the possible inhibitory effects of the E4 11k/Ddx6 interaction on RIG-I during an adenovirus infection. Cells will be infected with wild type or E4 11k-deletion mutants of adenovirus and then harvested for qRT-PCR at various hours post infection using primers for RIG-I, IFN-ß, GAPDH, and the virus associated RNA (VA1). Our results will help to create a better understanding of how the host innate immune response is activated and possibly subverted in DNA viruses.


GCSU Dept. of Environmental and Biological Sciences

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