Intrinsic Antiviral Activity of Optineurin Prevents Hyperproliferation of a Primary Herpes Simplex Virus Type 2 Infection.

Journal Article (Journal Article)

Very little knowledge exists on virus-specific host cell intrinsic mechanisms that prevent hyperproliferation of primary HSV type 2 (HSV-2) genital infections. In this study, we provide evidence that the Nemo-related protein, optineurin (OPTN), plays a key role in restricting HSV-2 infection both in vitro and in vivo. Contrary to previous reports regarding the proviral role of OPTN during Sendai virus infection, we demonstrate that lack of OPTN in cells causes enhanced virus production. OPTN deficiency negatively affects the host autophagy response and results in a marked reduction of CCL5 induction. OPTN knockout (OPTN-/- ) mice display exacerbated genital disease and dysregulated T cell frequencies in infected tissues and lymph nodes. A human transcriptomic profile dataset provides further credence that a strong positive correlation exists between CCL5 upregulation and OPTN expression during HSV-2 genital infection. Our findings underscore a previously unknown OPTN/CCL5 nexus that restricts hyperproliferative spread of primary HSV-2 infection, which may constitute an intrinsic host defense mechanism against herpesviruses in general.

Full Text

Duke Authors

Cited Authors

  • Patil, CD; Suryawanshi, R; Ames, J; Koganti, R; Agelidis, A; Kapoor, D; Yadavalli, T; Koujah, L; Tseng, HC; Shukla, D

Published Date

  • January 2022

Published In

Volume / Issue

  • 208 / 1

Start / End Page

  • 63 - 73

PubMed ID

  • 34880107

Pubmed Central ID

  • PMC9015683

Electronic International Standard Serial Number (EISSN)

  • 1550-6606

International Standard Serial Number (ISSN)

  • 0022-1767

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.2100472

Language

  • eng