The role of PI3K/Akt in human herpesvirus infection: From the bench to the bedside

Virology. 2015 May;479-480:568-77. doi: 10.1016/j.virol.2015.02.040. Epub 2015 Mar 20.

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.

Keywords: Akt; Cytomegalovirus; Epstein-Barr virus; Herpes simplex; Herpesvirus; Kaposi׳s sarcoma associated herpesvirus; PI3K; Varicella-zoster.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Antiviral Agents / pharmacology
  • Herpesviridae / physiology*
  • Herpesviridae Infections / drug therapy
  • Host-Pathogen Interactions*
  • Humans
  • Oncogene Protein v-akt / antagonists & inhibitors
  • Oncogene Protein v-akt / metabolism*
  • Phosphatidylinositol 3-Kinase / metabolism*
  • Phosphoinositide-3 Kinase Inhibitors
  • Signal Transduction
  • Viral Proteins / metabolism*
  • Virus Latency*
  • Virus Replication*

Substances

  • Antiviral Agents
  • Phosphoinositide-3 Kinase Inhibitors
  • Viral Proteins
  • Phosphatidylinositol 3-Kinase
  • Oncogene Protein v-akt