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THE ROLE OF ADENOVIRUS PROTEIN E4 11K IN P BODY PROTEIN RELOCALIZATION**

Abstract

Adenoviruses (Ad) can cause diseases, such as the common cold and conjunctivitis. E4 11k is an important viral protein that regulates late gene expression. E4 11k has been shown to disrupt cellular function by relocalizing processing body (p body) proteins to cytoplasmic aggresomes. Aggresomes 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 Ad infection. Ddx6, however, was not relocalized to cadmium chloride (CdCl2)-induced 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 (A549) cells following wild-type Ad infection and 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. Additionally, we infected A549 cells with three E4 11k-expressing viruses: E4 11k (wild-type), L103A mutant, and D105A/L106A (DL) mutant viruses. The L103A mutant cannot oligomerize but has the ability to dimerize, while the DL mutant virus displays some form of multimerization. Current observations indicate that E4 11k is necessary and sufficient to relocalize Ddx6 to the aggresome and that the level of protein folding present may affect certain functions of p body relocalization. Using these mutant viruses, 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. We hope to better understand the dynamics of p body and aggresome formation in human cells.

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