OPTN is a host intrinsic restriction factor against neuroinvasive HSV-1 infection.

Journal Article (Journal Article)

Fast-replicating neurotropic herpesviruses exemplified by herpes simplex virus-1 (HSV-1) naturally infect the central nervous system (CNS). However, most individuals intrinsically suppress the virus during a primary infection and preclude it from significantly damaging the CNS. Optineurin (OPTN) is a conserved autophagy receptor with little understanding of its role in neurotropic viral infections. We show that OPTN selectively targets HSV-1 tegument protein, VP16, and the fusion glycoprotein, gB, to degradation by autophagy. OPTN-deficient mice challenged with HSV-1 show significant cognitive decline and susceptibility to lethal CNS infection. OPTN deficiency unveils severe consequences for recruitment of adaptive immunity and suppression of neuronal necroptosis. Ocular HSV-1 infection is lethal without OPTN and is rescued using a necroptosis inhibitor. These results place OPTN at the crux of neuronal survival from potentially lethal CNS viral infections.

Full Text

Duke Authors

Cited Authors

  • Ames, J; Yadavalli, T; Suryawanshi, R; Hopkins, J; Agelidis, A; Patil, C; Fredericks, B; Tseng, H; Valyi-Nagy, T; Shukla, D

Published Date

  • September 13, 2021

Published In

Volume / Issue

  • 12 / 1

Start / End Page

  • 5401 -

PubMed ID

  • 34518549

Pubmed Central ID

  • PMC8437952

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/s41467-021-25642-z

Language

  • eng

Conference Location

  • England