The Role of Adenovirus Protein E4 11k in P Body Protein Relocalization
Faculty Mentor(s) Name(s)
Kasey Karen
Abstract
Adenovirus serotype 5 (Ad5) is a double-stranded DNA virus that can cause upper respiratory infections and conjunctivitis. One of the viral proteins, E4 11k, supports early viral infection by promoting late gene expression. E4 11k has been shown to disrupt cellular function by relocalizing processing body (p body) proteins to cytoplasmic aggresomes. Aggresomes are perinuclear formations that are sites of misfolded protein storage and only arise when there is cellular stress. The scaffolding p body protein, Ddx6, has been shown to colocalize with E4 11k in aggresomes during a wild-type Ad5 infection. Ddx6, however, was not relocalized to chemically induced (cadmium chloride-treated) aggresomes. This suggests that E4 11k is necessary for the relocalization of Ddx6. We observed the localization of additional p body proteins, Lsm1, Edc3, and Pat1b, in human lung carcinoma cells following wild-type Ad5 infection and cadmium chloride (CdCl2 ) treatment. Lsm1 and Edc3 were relocalized to both infection and chemically induced aggresomes. Pat1b, however, was not relocalized to either infection or chemically induced aggresomes. To further characterize the role of E4 11k in p body localization, we will infect with E4 11k only, L103A mutant, and D105A L106A mutant viruses and observe the localization of several p body proteins. Currently, the ability of L103A and D105A L106A mutant viruses to induce aggresome formation has not been studied. The L103A mutant cannot oligomerize but has the ability to dimerize. Using this mutant virus, we hope to determine if the oligomerization from E4 11k is required for aggresome formation. In addition, we want to observe the different p body proteins to determine if their localization during mutant virus infection is altered. The study’s significance is to understand better the dynamics of p body and aggresome formation in human cells.
Start Date
27-3-2024 10:00 AM
End Date
27-3-2024 10:50 AM
Location
Magnolia Ballroom
The Role of Adenovirus Protein E4 11k in P Body Protein Relocalization
Magnolia Ballroom
Adenovirus serotype 5 (Ad5) is a double-stranded DNA virus that can cause upper respiratory infections and conjunctivitis. One of the viral proteins, E4 11k, supports early viral infection by promoting late gene expression. E4 11k has been shown to disrupt cellular function by relocalizing processing body (p body) proteins to cytoplasmic aggresomes. Aggresomes are perinuclear formations that are sites of misfolded protein storage and only arise when there is cellular stress. The scaffolding p body protein, Ddx6, has been shown to colocalize with E4 11k in aggresomes during a wild-type Ad5 infection. Ddx6, however, was not relocalized to chemically induced (cadmium chloride-treated) aggresomes. This suggests that E4 11k is necessary for the relocalization of Ddx6. We observed the localization of additional p body proteins, Lsm1, Edc3, and Pat1b, in human lung carcinoma cells following wild-type Ad5 infection and cadmium chloride (CdCl2 ) treatment. Lsm1 and Edc3 were relocalized to both infection and chemically induced aggresomes. Pat1b, however, was not relocalized to either infection or chemically induced aggresomes. To further characterize the role of E4 11k in p body localization, we will infect with E4 11k only, L103A mutant, and D105A L106A mutant viruses and observe the localization of several p body proteins. Currently, the ability of L103A and D105A L106A mutant viruses to induce aggresome formation has not been studied. The L103A mutant cannot oligomerize but has the ability to dimerize. Using this mutant virus, we hope to determine if the oligomerization from E4 11k is required for aggresome formation. In addition, we want to observe the different p body proteins to determine if their localization during mutant virus infection is altered. The study’s significance is to understand better the dynamics of p body and aggresome formation in human cells.