Herpes simplex virus type 2 encodes a heat shock protein homologue with apoptosis regulatory functions.
The decision to undergo apoptosis lies in the balance between pro- and anti-apoptotic proteins. Since virus replication relies on the cellular machinery, viruses have evolved various strategies to alter this balance. They target the Bcl-2 and signaling protein kinase (PK) apoptosis modulatory families by encoding homologues or altering the expression of the cellular proteins. The heat shock proteins (Hsp) are emerging as a new family of apoptosis modulatory proteins and are also a target of virus modification. Hsp function in protein folding and activation, often assisted by co-chaperones. They complex with nascent or damaged proteins and chaperone them for refolding and resumption of function, or for proteosomal degradation. Until recently, Hsp were considered strictly anti-apoptotic, possibly by virtue of their contribution to the removal of damaged and undesirable client proteins. However, recent studies have also begun to associate the Hsp with pro-apoptotic functions. Herpes simplex virus type 2 (HSV-2) encodes two proteins homologous to Hsp family members. One of these, known as ICP10PK, is a homologue to a newly cloned Hsp (H11) and modulates virus-induced apoptosis. ICP10PK is unique among the viral proteins that regulate apoptosis in that it targets all the families of apoptosis modulatory proteins. It activates the ERK signaling pathway, stabilizes Bcl-2 and upregulates Hsp70 and Hsp27 as well as the Hsp70 co-chaperone Bag-1. Its ability to commander these families of apoptosis regulators is required for HSV-2 replication and latency establishment/reactivation.
Gober
Michael D
MD
Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, MD 21201, USA. mgobe001@umaryland.edu
Wales
Samantha Q
SQ
Aurelian
Laure
L
D017209:Apoptosis / Q000502:physiology*; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000276:immunology / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D018258:Herpesvirus 2, Human / Q000502:physiology*; D006801:Humans; D007107:Immune System; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000276:immunology / Q000378:metabolism
D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins