Xenophagy in herpes simplex virus replication and pathogenesis.
Autophagy functions in part as an important host defense mechanism to engulf and degrade intracellular pathogens, a process that has been termed xenophagy. Xenophagy is detrimental to the invading microbe in terms of replication and pathogenesis and many pathogens either dampen the autophagic response, or utilize the pathway to enhance their life cycle. Herpes simplex virus type 1 (HSV-1) counteracts the induction of xenophagy through its neurovirulence protein, ICP34.5. ICP34.5 binds protein phosphatase 1alpha to counter PKR-mediated phosphorylation of eIF2alpha, and also binds the autophagy-promoting protein Beclin 1. Through these interactions, ICP34.5 prevents translational arrest and down-regulates the formation of autophagosomes. Whereas autophagy antagonism promotes neurovirulence, it has no impact on the replication of HSV-1 in permissive cultured cells. As discussed in this article, this work raises a number of questions as to the mechanism of ICP34.5-mediated inhibition of autophagy, as well as to the role of autophagy antagonism in the lifecycle of HSV-1.
Alexander
Diane E
DE
Department of Ophthalmology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Leib
David A
DA
D000818:Animals; D051017:Apoptosis Regulatory Proteins; D001343:Autophagy / Q000502:physiology*; D000071187:Autophagy-Related Protein 5; D000071186:Beclin-1; D005347:Fibroblasts / Q000378:metabolism / Q000648:ultrastructure; D018259:Herpesvirus 1, Human / Q000502:physiology*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication
D051017:Apoptosis Regulatory Proteins; C495773:Atg5 protein, mouse; D000071187:Autophagy-Related Protein 5; D000071186:Beclin-1; C115010:Becn1 protein, mouse; D008869:Microtubule-Associated Proteins; D011506:Proteins; D014764:Viral Proteins; C066469:gamma 34.5 protein, Human herpesvirus 1