title: The pros and cons of autophagic flux among herpesviruses.
abstract: Autophagy has been intensively studied in herpes simplex virus type 1 (HSV-1), a human alphaherpesvirus. The HSV-1 genome encodes a well-known neurovirulence protein called ICP34.5. When the gene encoding this protein is deleted from the genome, the virus is markedly less virulent when injected into the brains of animal models. Subsequent characterization of ICP34.5 established that the neurovirulence protein interacts with BECN1, thereby inhibiting autophagy and facilitating viral replication in the brain. However, an ortholog of the ICP34.5 gene is lacking in the genomes of other closely related alphaherpesviruses, such as varicella-zoster virus (VZV). Further, autophagosomes are easily identified in the exanthem (rash) that is the hallmark of both VZV diseases-varicella and herpes zoster. Inhibition of autophagy leads to diminished VZV titers. Finally, no block is detected in studies of autophagic flux following VZV infection. Thus autophagy appears to be proviral during VZV infection while antiviral during HSV-1 infection. Because divergence to this degree is extremely unusual for 2 closely related herpesviruses, we postulate that VZV has accommodated its infectious cycle to benefit from autophagic flux, whereas HSV-1 has captured cellular immunomodulatory genes to inhibit autophagy.
authors.affiliation: a Virology Laboratory; Children's Hospital; University of Iowa ; Iowa City , IA USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Grose
authors.forename: Erin M
authors.initials: EM
authors.lastname: Buckingham
authors.forename: Wallen
authors.initials: W
authors.lastname: Jackson
authors.forename: John E
authors.initials: JE
authors.lastname: Carpenter
mesh_terms: D000818:Animals; D001343:Autophagy / Q000235:genetics / Q000502:physiology*; D006562:Herpes Zoster / Q000821:virology*; D006564:Herpesviridae; D018259:Herpesvirus 1, Human; D006801:Humans; D051379:Mice; D014764:Viral Proteins / Q000378:metabolism*; D014779:Virus Replication / Q000235:genetics / Q000502:physiology*
chemical_list: D014764:Viral Proteins
keywords: Epstein-Barr virus; autophagy; herpes simplex virus; lysosome; varicella-zoster virus