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. ? ?
| Skalet, Alison H; Isler, Jennifer A; King, Leslie B et al. (2005) Rapid B cell receptor-induced unfolded protein response in nonsecretory B cells correlates with pro- versus antiapoptotic cell fate. J Biol Chem 280:39762-71 |
| Isler, Jennifer A; Maguire, Tobi Goldberg; Alwine, James C (2005) Production of infectious human cytomegalovirus virions is inhibited by drugs that disrupt calcium homeostasis in the endoplasmic reticulum. J Virol 79:15388-97 |
| Isler, Jennifer A; Skalet, Alison H; Alwine, James C (2005) Human cytomegalovirus infection activates and regulates the unfolded protein response. J Virol 79:6890-9 |
