title: The role of PI3K/Akt in human herpesvirus infection: From the bench to the bedside.
abstract: The phosphatidylinositol-3-kinase (PI3K)-Akt signaling pathway regulates several key cellular functions including protein synthesis, cell growth, glucose metabolism, and inflammation. Many viruses have evolved mechanisms to manipulate this signaling pathway to ensure successful virus replication. The human herpesviruses undergo both latent and lytic infection, but differ in cell tropism, growth kinetics, and disease manifestations. Herpesviruses express multiple proteins that target the PI3K/Akt cell signaling pathway during the course of their life cycle to facilitate viral infection, replication, latency, and reactivation. Rare human genetic disorders with mutations in either the catalytic or regulatory subunit of PI3K that result in constitutive activation of the protein predispose to severe herpesvirus infections as well as to virus-associated malignancies. Inhibiting the PI3K/Akt pathway or its downstream proteins using drugs already approved for other diseases can block herpesvirus lytic infection and may reduce malignancies associated with latent herpesvirus infections.
authors: Medical Virology Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
authors: XueQiao
authors: X
authors: Liu
authors: Medical Virology Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA. Electronic address: jcohen@niaid.nih.gov.
authors: Jeffrey I
authors: JI
authors: Cohen
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology; D006564:Herpesviridae / Q000502:physiology*; D006566:Herpesviridae Infections / Q000188:drug therapy; D054884:Host-Pathogen Interactions; D006801:Humans; D051058:Oncogene Protein v-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D015398:Signal Transduction; D014764:Viral Proteins / Q000378:metabolism*; D017735:Virus Latency; D014779:Virus Replication
chemical_list: D000998:Antiviral Agents; D000081082:Phosphoinositide-3 Kinase Inhibitors; D014764:Viral Proteins; D058539:Phosphatidylinositol 3-Kinase; D051058:Oncogene Protein v-akt
keywords: Akt; Cytomegalovirus; Epstein-Barr virus; Herpes simplex; Herpesvirus; Kaposi׳s sarcoma associated herpesvirus; PI3K; Varicella-zoster