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

Publication ,  Journal Article
Ames, J; Yadavalli, T; Suryawanshi, R; Hopkins, J; Agelidis, A; Patil, C; Fredericks, B; Tseng, H; Valyi-Nagy, T; Shukla, D
Published in: Nat Commun
September 13, 2021

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.

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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

September 13, 2021

Volume

12

Issue

1

Start / End Page

5401

Location

England

Related Subject Headings

  • Virus Replication
  • Vero Cells
  • RNA Interference
  • Neuroprotective Agents
  • Neurons
  • Necroptosis
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Membrane Transport Proteins
 

Citation

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Ames, J., Yadavalli, T., Suryawanshi, R., Hopkins, J., Agelidis, A., Patil, C., … Shukla, D. (2021). OPTN is a host intrinsic restriction factor against neuroinvasive HSV-1 infection. Nat Commun, 12(1), 5401. https://doi.org/10.1038/s41467-021-25642-z
Ames, Joshua, Tejabhiram Yadavalli, Rahul Suryawanshi, James Hopkins, Alexander Agelidis, Chandrashekhar Patil, Brian Fredericks, Henry Tseng, Tibor Valyi-Nagy, and Deepak Shukla. “OPTN is a host intrinsic restriction factor against neuroinvasive HSV-1 infection.Nat Commun 12, no. 1 (September 13, 2021): 5401. https://doi.org/10.1038/s41467-021-25642-z.
Ames J, Yadavalli T, Suryawanshi R, Hopkins J, Agelidis A, Patil C, et al. OPTN is a host intrinsic restriction factor against neuroinvasive HSV-1 infection. Nat Commun. 2021 Sep 13;12(1):5401.
Ames, Joshua, et al. “OPTN is a host intrinsic restriction factor against neuroinvasive HSV-1 infection.Nat Commun, vol. 12, no. 1, Sept. 2021, p. 5401. Pubmed, doi:10.1038/s41467-021-25642-z.
Ames J, Yadavalli T, Suryawanshi R, Hopkins J, Agelidis A, Patil C, Fredericks B, Tseng H, Valyi-Nagy T, Shukla D. OPTN is a host intrinsic restriction factor against neuroinvasive HSV-1 infection. Nat Commun. 2021 Sep 13;12(1):5401.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

September 13, 2021

Volume

12

Issue

1

Start / End Page

5401

Location

England

Related Subject Headings

  • Virus Replication
  • Vero Cells
  • RNA Interference
  • Neuroprotective Agents
  • Neurons
  • Necroptosis
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Membrane Transport Proteins