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Updated: Oct 10, 2025
A Primary Neuron Culture System for the Study of Herpes Simplex Virus Latency and Reactivation
Published on: April 2, 2012
Intrinsic Antiviral Activity of Optineurin Prevents Hyperproliferation of a Primary Herpes Simplex Virus Type 2
Chandrashekhar D Patil1, Rahul Suryawanshi1, Joshua Ames1,2
1Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL.
Abstract:
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.
Insights
Optineurin (OPTN) restricts herpes simplex virus type 2 (HSV-2) genital infections by enhancing autophagy and CCL5 induction. OPTN deficiency exacerbates disease, highlighting its role in intrinsic host defense against HSV-2.
Area of Science:
- Virology
- Immunology
- Cell Biology
Background:
- Limited understanding of host cell mechanisms controlling herpes simplex virus type 2 (HSV-2) genital infections.
- Optineurin (OPTN) has been reported to play a proviral role in other viral infections.
Purpose of the Study:
- To investigate the role of optineurin (OPTN) in restricting primary HSV-2 genital infections.
- To elucidate the intrinsic host cell mechanisms involving OPTN during HSV-2 infection.
Main Methods:
- In vitro and in vivo studies using cell cultures and OPTN knockout (OPTN-/-) mice.
- Analysis of viral production, autophagy response, CCL5 induction, and T cell frequencies.
- Examination of human transcriptomic data.
Main Results:
- OPTN deficiency led to enhanced HSV-2 production in vitro.
- OPTN knockout mice exhibited exacerbated genital disease and altered T cell responses.
- OPTN deficiency impaired autophagy and reduced CCL5 induction.
- Human data confirmed a positive correlation between CCL5 and OPTN expression in HSV-2 infection.
Conclusions:
- Optineurin (OPTN) acts as a crucial intrinsic host factor restricting HSV-2 replication and spread.
- The OPTN/CCL5 pathway is identified as a novel mechanism limiting hyperproliferative HSV-2 infection.
- Findings suggest a potential host defense strategy against herpesviruses.
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