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POTENTIAL ROLE OF ADENOVIRUS E4 11K PROTEIN IN THE RIG-I-MEDIATED TYPE 1 INTERFERON RESPONSE**

Abstract

Adenoviruses are double-stranded DNA viruses that most commonly cause upper respiratory illnesses, such as a common cold. During the early phase of an adenovirus infection, it creates an ideal environment to promote viral replication. One of the ways adenoviruses accomplishes this is through the viral protein, E4 11k, which has several functions, including redistributing proteins in cellular bodies, such as p bodies and PML nuclear bodies, as well as inhibiting double-strand break repair. The cell attempts to respond to an infection through viral RNA sensors that can activate a type 1 interferon response, which can produce proteins to interfere with viral replication. Retinoic-acid inducible gene I (RIG-I) is a viral RNA sensor that activates interferon beta, which then can induce a type 1 interferon response. DEAD-box helicase 6 (Ddx6) is known to bind to RIG-I to amplify its function. Other viruses, such as influenza and EV71, have been shown to modulate RIG-I through Ddx6. As Ad E4 11k is known to bind to Ddx6, we hypothesize that adenovirus also modulates RIG-I through Ddx6, preventing a type 1 interferon response from occurring. A549 cells were infected for 52 hours, and qRT-PCR was used to determine RIG-I and interferon beta levels, as compared to GAPDH. We found a 25-fold and 4-fold increase in RIG-I and interferon beta gene expression, respectively, in a virus lacking expression of E4 11k compared to wild-type virus. Further analysis using two different viral mutants lacking expression of E4 11k, as well as an expression vector that essentially only expresses E4 11k, along with numerous infection periods, is currently underway to demonstrate the potential role of E4 11k in RIG-I activation and interferon beta expression. This would be the first time a DNA virus has been observed modulating an RNA sensor of viral infection through Ddx6.

Acknowledgements

GCSU department of biological and envrionmental sciences

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