Role of Innate Interferon Responses at the Ocular Surface in Herpes Simplex Virus-1-Induced Herpetic Stromal Keratitis

Herpes simplex virus type 1 (HSV-1) is a highly successful pathogen that primarily infects epithelial cells of the orofacial mucosa. After initial lytic replication, HSV-1 enters sensory neurons and undergoes lifelong latency in the trigeminal ganglion (TG). Reactivation from latency occurs throughout the host’s life and is more common in people with a compromised immune system. HSV-1 causes various diseases depending on the site of lytic HSV-1 replication. These include herpes labialis, herpetic stromal keratitis (HSK), meningitis, and herpes simplex encephalitis (HSE). HSK is an immunopathological condition and is usually the consequence of HSV-1 reactivation, anterograde transport to the corneal surface, lytic replication in the epithelial cells, and activation of the host’s innate and adaptive immune responses in the cornea. HSV-1 is recognized by cell surface, endosomal, and cytoplasmic pattern recognition receptors (PRRs) and activates innate immune responses that include interferons (IFNs), chemokine and cytokine production, as well as the recruitment of inflammatory cells to the site of replication. In the cornea, HSV-1 replication promotes type I (IFN-α/β) and type III (IFN-λ) IFN production. This review summarizes our current understanding of HSV-1 recognition by PRRs and innate IFN-mediated antiviral immunity during HSV-1 infection of the cornea. We also discuss the immunopathogenesis of HSK, current HSK therapeutics and challenges, proposed experimental approaches, and benefits of promoting local IFN-λ responses.

• Publication year

  2023

• Venue

  Pathogens

• Publication date

  2023-03-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.3390/pathogens12030437PMID 36986359PMCID 10058014
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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  2022cited by this paper
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  2022cited by this paper
• Fraternal Twins: The Enigmatic Role of the Immune System in Alphaherpesvirus Pathogenesis and Latency and Its Impacts on Vaccine Efficacy

  2022influential reference
• Cytoplasmic RNA sensors and their interplay with RNA-binding partners in innate antiviral response: theme and variations

  2022cited by this paper
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• Cellular origins of dsRNA, their recognition and consequences

  2021cited by this paper
• Pattern recognition receptors in health and diseases

  2021cited by this paper
• Viral tegument proteins restrict cGAS-DNA phase separation to mediate immune evasion.

  2021cited by this paper
• Pathogenesis and virulence of herpes simplex virus

  2021cited by this paper
• IFN-λ Regulates Neutrophil Biology to Suppress Inflammation in Herpes Simplex Virus-1–Induced Corneal Immunopathology

  2021influential reference
• Herpes Simplex Virus Cell Entry Mechanisms: An Update

  2021cited by this paper
• Herpes Simplex Virus and Pattern Recognition Receptors: An Arms Race

  2021cited by this paper
• Crosstalk Between Epithelial Cells, Neurons and Immune Mediators in HSV-1 Skin Infection

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• The cGAS–STING pathway as a therapeutic target in inflammatory diseases

  2021cited by this paper
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  2021cited by this paper
• Estimates of the Prevalence and Incidence of Genital Herpes, United States, 2018.

  2021cited by this paper
• Herpes simplex virus 1 evades cellular antiviral response by inducing microRNA-24, which attenuates STING synthesis

  2021cited by this paper
• Herpes Simplex Virus 1 Infection of Neuronal and Non-Neuronal Cells Elicits Specific Innate Immune Responses and Immune Evasion Mechanisms

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• Herpesviruses and the Type III Interferon System

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• HSV-1 DNA Replication—Coordinated Regulation by Viral and Cellular Factors

  2021cited by this paper
• Viperin has species-specific roles in response to herpes simplex virus infection

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• Inhibiting Glucose Metabolism Results in Herpes Simplex Encephalitis

  2021cited by this paper
• Broadly Antiviral Activities of TAP1 through Activating the TBK1-IRF3-Mediated Type I Interferon Production

  2021cited by this paper
• Pathobiology and treatment of viral keratitis.

  2021cited by this paper
• Advancing Our Understanding of Corneal Herpes Simplex Virus-1 Immune Evasion Mechanisms and Future Therapeutics

  2021cited by this paper
• Developments in Vaccination for Herpes Simplex Virus

  2021cited by this paper
• Relative Contributions of the cGAS-STING and TLR3 Signaling Pathways to Attenuation of Herpes Simplex Virus 1 Replication

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  2020cited by this paper
• All About the RNA: Interferon-Stimulated Genes That Interfere With Viral RNA Processes

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• HSV-1 and Zika Virus but Not SARS-CoV-2 Replicate in the Human Cornea and Are Restricted by Corneal Type III Interferon

  2020cited by this paper
• Surgical Alternatives to Keratoplasty in Microbial Keratitis.

  2020cited by this paper
• Characterization of Resident Corneal Plasmacytoid Dendritic Cells and Their Pivotal Role in Herpes Simplex Keratitis

  2020cited by this paper
• Herpes Simplex Virus Type 1 Interactions with the Interferon System

  2020influential reference
• The Role of VP16 in the Life Cycle of Alphaherpesviruses

  2020cited by this paper
• Potent Antiviral Activity against HSV-1 and SARS-CoV-2 by Antimicrobial Peptoids

  2020cited by this paper
• Herpes Simplex Virus-1 in the Brain: The Dark Side of a Sneaky Infection.

  2020cited by this paper
• Pathogenesis of Herpes Stromal Keratitis: Immune Inflammatory Response Mediated by Inflammatory Regulators

  2020cited by this paper
• Herpes Simplex Virus: The Hostile Guest That Takes Over Your Home

  2020cited by this paper
• Herpes simplex virus: global infection prevalence and incidence estimates, 2016

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• TRIM21 Aggravates Herpes Simplex Virus Epithelial Keratitis by Attenuating STING-IRF3-Mediated Type I Interferon Signaling

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  2020cited by this paper
• Increased phagocytosis in the presence of enhanced M2-like macrophage responses correlates with increased primary and latent HSV-1 infection

  2020cited by this paper
• Herpesvirus latency.

  2020cited by this paper
• RIG-I-like receptors: their regulation and roles in RNA sensing

  2020cited by this paper
• Toll-like receptor-mediated innate immunity against herpesviridae infection: a current perspective on viral infection signaling pathways

  2020cited by this paper
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• Interferon-λ orchestrates innate and adaptive mucosal immune responses

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• The Role of T Cells in Herpes Stromal Keratitis

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• Shared and Distinct Functions of Type I and Type III Interferons.

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• Decoding type I and III interferon signalling during viral infection

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