EXAMINING THE ROLE OF ADENOVIRUS E4 11K PROTEIN ON INTERFERON-BETA EXPRESSION**

Authors

Odeya Atar*, Georgia College & State University, Milledgeville, GA 31061Follow
Lily M. Cox*, Georgia College & State University, Milledgeville, GA 31061Follow
Kasey A. Karen, Georgia College & State University, Milledgeville, GA 31061Follow

Abstract

Adenoviruses are double-stranded DNA viruses known to cause conjunctivitis and the common cold. To create conditions favorable for viral replication, adenovirus expresses a series of early viral proteins, including E4 11K, which alters cellular structures by redistributing PML nuclear bodies and cytoplasmic P bodies. Viral infections activate nucleic acid sensors, leading to the inhibition of viral replication. RIG-I is a viral RNA sensor that triggers a signaling cascade to stimulate a type I interferon response. Previous works have demonstrated that RIG-I activation is enhanced by its interaction with DEAD-box helicase (Ddx6), inducing type I interferon responses. Furthermore, E4 11k has been shown to colocalize with and bind to Ddx6, causing Ddx6 to enter aggresomes. It is hypothesized that E4 11k binds to Ddx6 to modulate RIG-I, leading to a reduction in interferon-beta expression. To test this, human lung carcinoma cells (A549) are being infected with three virus variants: Ad5 wildtype, E4 11k-only, and E4 11k-deleted virus, and analyzed at 12, 24, 30, 36, and 48 hours post infection (hpi). Reverse transcription q-PCR is being performed to evaluate the expression of RIG-I and interferon-beta. Preliminary data using a normalization to an internal control shows biphasic expression of interferon-beta during the wildtype adenovirus infection. In the absence of E4 11k, a significant increase of interferon-beta was observed exclusively at 48 hpi (p =0.00113, ANOVA and Tukey). Once the data is consistent, knockdown experiments of Ddx6 and RIG-I will be performed to further validate the hypothesis. It is expected that the Ddx6 knockdown will reduce interferon-beta expression in the E4 11k deleted virus, while RIG-I knockdown will abolish the late-phase interferon response completely. These planned experiments will clarify if E4 11k-dependent reduction of interferon-beta depends on the Ddx6-RIG-I interaction.

Acknowledgements

GCSU Department of Biological and Environmental Sciences, Tri-Beta Undergraduate Research Grant

Recommended Citation

Atar*, Odeya; Cox*, Lily M.; and Karen, Kasey A. (2026) "EXAMINING THE ROLE OF ADENOVIRUS E4 11K PROTEIN ON INTERFERON-BETA EXPRESSION**," Georgia Journal of Science, Vol. 84, No. 1, Article 85.
Available at: https://digitalcommons.gaacademy.org/gjs/vol84/iss1/85