title: Modulation of host cell stress responses by human cytomegalovirus.
abstract: Human cytomegalovirus (HCMV) induces cellular stress responses during infection due to nutrient depletion, energy depletion, hypoxia and synthetic stress, e.g., endoplasmic reticulum (ER) stress. Cellular stress responses initiate processes that allow the cell to survive the stress; some of these may be beneficial to HCMV replication while others are not. Several studies show that HCMV manipulates stress response signaling in order to maintain beneficial effects while inhibiting detrimental effects. The inhibition of translation is the most common effect of stress responses that would be detrimental to HCMV infection. This chapter will focus on the mechanisms by which cap-dependent translation is maintained during HCMV infection through alterations of the phosphatidylinositol-3' kinase (PI3K)-Akt-tuberous sclerosis complex (TSC)-mammalian target of rapamycin (mTOR) signaling pathway. The emerging picture is that HCMV affects this pathway in multiple ways, thus ensuring that cap-dependent translation is maintained despite the induction of stress responses that would normally inhibit it. Such dramatic alterations of this pathway lead to questions of what other beneficial effects the virus might gain from these changes and how these changes may contribute to HCMV pathogenesis.
authors.affiliation: Department of Cancer Biology, University of Pennsylvania, 314 Biomedical Research Building, 421 Curie Blvd. Philadelphia, PA 19104-6142, USA. alwine@mail.med.upenn.edu
authors.forename: J C
authors.initials: JC
authors.lastname: Alwine
mesh_terms: D003587:Cytomegalovirus / Q000502:physiology*; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D014176:Protein Biosynthesis; D011494:Protein Kinases / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D011494:Protein Kinases; D058570:TOR Serine-Threonine Kinases; D025521:Tumor Suppressor Proteins; C546842:MTOR protein, human