Human Cytomegalovirus and the Unfolded Protein Response

University Of Pennsylvania, Philadelphia PA

Investigators

Linked publications & trials

Abstract

[unreadable] DESCRIPTION (provided by applicant): Like other DNA viruses, HCMV utilizes host cell machinery to efficiently express the products of its genome. The increased production of viral proteins during viral infection leads to stress in the endoplasmic reticulum (ER) and can activate a cellular stress response known as the unfolded protein response (UPR). In an effort to relieve ER stress, effectors of the UPR shut down protein translation and promote cell cycle arrest, conditions which do not support viral replication. Thus, the virus needs to adapt or counteract these effects to sustain a productive infection. Our data, and the data of others, suggest that HCMV immediate early proteins target critical cellular regulators and alter the processes they control to benefit viral infection. Using the HCMV model system, the overall goal of this project is to determine the relationship between viral regulatory mechanisms and the cellular stress response. Specifically, we propose to (i) determine whether HCMV activates the UPR and to identify UPR signaling components which may be modified during HCMV infection; (ii) determine whether HCMV infection persists in the presence of UPR activation; (iii) identify HCMV-encoded proteins that modify the UPR in order to sustain viral growth. [unreadable] [unreadable]