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

Joshua Ames, Tejabhiram Yadavalli, Rahul Suryawanshi, James Hopkins, Alexander Agelidis, Chandrashekhar Patil, Brian Fredericks, Henry Tseng, Tibor Valyi-Nagy, Deepak Shukla

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

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.

Original languageEnglish
Article number5401
JournalNature Communications
Volume12
Issue number1
DOIs
StatePublished - 1 Dec 2021
Externally publishedYes

ASJC Scopus subject areas

  • Physics and Astronomy (all)
  • Chemistry (all)
  • Biochemistry, Genetics and Molecular Biology (all)

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