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