POTENTIAL ROLE OF ADENOVIRUS E4 11K PROTEIN TOWARD THE INHIBITION OF INTERFERON-BETA EXPRESSION
Faculty Mentor(s) Name(s)
Kasey Karen
Abstract
Adenoviruses are double-stranded DNA viruses that cause common upper respiratory infections. Early viral proteins generate an ideal environment to promote viral replication. One early viral protein, E4 11k, has multiple functions, including the redistribution of promyelocytic leukemia (PML) nuclear bodies and cytoplasmic p bodies, leading to a potential alteration of their functions. The cell will attempt to respond to viral infection through nucleic acid sensors, such as retinoic-acid inducible gene I (RIG-I), that will induce type I interferon transcription, which can lead to inhibition of viral replication. RIG-I is a viral RNA sensor that activates a signaling cascade to stimulate a type I interferon response. DEAD-box helicase 6 (Ddx6) was recently shown to bind to RIG-I to enhance its functions. E4 11k has been shown to colocalize with and bind to Ddx6, causing Ddx6 to go into aggresomes. Influenza and EV71, both single-stranded RNA viruses, have also been shown to interact with Ddx6, leading to the modulation of RIG-I. Therefore, we hypothesize that E4 11k is binding to Ddx6 to modulate RIG-I, leading to a decrease of expression of interferon-beta. Human lung carcinoma cells (A549) were infected with an Ad 5 wild-type virus and an E4 11k deleted virus for 12, 24, 30, 36, or 48 hours, and RT-qPCR was performed to evaluate expression of RIG-I and IFNB1. When the expression of RIG-I and IFNB1 was normalized to GAPDH, an internal control, a biphasic expression of both RIG-I and IFNB1 was present during the wild-type infection with peaks at 24 and 36 hours post-infection (hpi) and was decreased at 30 and 40 hpi. When E4 11k was not present, a similar expression pattern occurred; however, there was a sustained increase of IFNB1 expression present after 36 hpi, suggesting that E4 11k is necessary toward the reduction of interferon-beta protein expression.
Start Date
27-3-2024 9:00 AM
End Date
27-3-2024 9:50 AM
Location
Magnolia Ballroom
POTENTIAL ROLE OF ADENOVIRUS E4 11K PROTEIN TOWARD THE INHIBITION OF INTERFERON-BETA EXPRESSION
Magnolia Ballroom
Adenoviruses are double-stranded DNA viruses that cause common upper respiratory infections. Early viral proteins generate an ideal environment to promote viral replication. One early viral protein, E4 11k, has multiple functions, including the redistribution of promyelocytic leukemia (PML) nuclear bodies and cytoplasmic p bodies, leading to a potential alteration of their functions. The cell will attempt to respond to viral infection through nucleic acid sensors, such as retinoic-acid inducible gene I (RIG-I), that will induce type I interferon transcription, which can lead to inhibition of viral replication. RIG-I is a viral RNA sensor that activates a signaling cascade to stimulate a type I interferon response. DEAD-box helicase 6 (Ddx6) was recently shown to bind to RIG-I to enhance its functions. E4 11k has been shown to colocalize with and bind to Ddx6, causing Ddx6 to go into aggresomes. Influenza and EV71, both single-stranded RNA viruses, have also been shown to interact with Ddx6, leading to the modulation of RIG-I. Therefore, we hypothesize that E4 11k is binding to Ddx6 to modulate RIG-I, leading to a decrease of expression of interferon-beta. Human lung carcinoma cells (A549) were infected with an Ad 5 wild-type virus and an E4 11k deleted virus for 12, 24, 30, 36, or 48 hours, and RT-qPCR was performed to evaluate expression of RIG-I and IFNB1. When the expression of RIG-I and IFNB1 was normalized to GAPDH, an internal control, a biphasic expression of both RIG-I and IFNB1 was present during the wild-type infection with peaks at 24 and 36 hours post-infection (hpi) and was decreased at 30 and 40 hpi. When E4 11k was not present, a similar expression pattern occurred; however, there was a sustained increase of IFNB1 expression present after 36 hpi, suggesting that E4 11k is necessary toward the reduction of interferon-beta protein expression.