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

Ren, Jiayi; Antony, Ferrin; Rouse, Barry T.; Suryawanshi, Amol

doi:10.3390/pathogens12030437

Cited by 13 publications

(7 citation statements)

References 376 publications

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“…Therefore, we concentrated on researching how the HSV-1 gene ICP27 affects hTert-RPE 1 cells' AIM 2 inflammasome pathway. Not only are hTert-RPE 1 cells target cells during primary HSV-1 infection at the ocular level, but they also modulate the immune response by releasing a variety of cytokines that affect the inflammatory response of neighboring immune cells, including macrophages, dendritic cells, and NK cells, which are located close to the retinal epithelial barrier [63][64][65][66].…”

Section: Discussionmentioning

confidence: 99%

Herpes Simplex Virus ICP27 Protein Inhibits AIM 2-Dependent Inflammasome Influencing Pro-Inflammatory Cytokines Release in Human Pigment Epithelial Cells (hTert-RPE 1)

Caproni,

Nordi,

Fontana

et al. 2024

IJMS

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Although Herpes simplex virus type 1 (HSV-1) has been deeply studied, significant gaps remain in the fundamental understanding of HSV-host interactions: our work focused on studying the Infected Cell Protein 27 (ICP27) as an inhibitor of the Absent-in-melanoma-2 (AIM 2) inflammasome pathway, leading to reduced pro-inflammatory cytokines that influence the activation of a protective innate immune response to infection. To assess the inhibition of the inflammasome by the ICP27, hTert-immortalized Retinal Pigment Epithelial cells (hTert-RPE 1) infected with HSV-1 wild type were compared to HSV-1 lacking functional ICP27 (HSV-1∆ICP27) infected cells. The activation of the inflammasome by HSV-1∆ICP27 was demonstrated by quantifying the gene and protein expression of the inflammasome constituents using real-time PCR and Western blot. The detection of the cleavage of the pro-caspase-1 into the active form was performed by using a bioluminescent assay, while the quantification of interleukins 1β (IL-1β) and 18 (IL-18)released in the supernatant was quantified using an ELISA assay. The data showed that the presence of the ICP27 expressed by HSV-1 induces, in contrast to HSV-1∆ICP27 vector, a significant downregulation of AIM 2 inflammasome constituent proteins and, consequently, the release of pro-inflammatory interleukins into the extracellular environment reducing an effective response in counteracting infection.

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Section: Discussionmentioning

confidence: 99%

Herpes Simplex Virus ICP27 Protein Inhibits AIM 2-Dependent Inflammasome Influencing Pro-Inflammatory Cytokines Release in Human Pigment Epithelial Cells (hTert-RPE 1)

Caproni,

Nordi,

Fontana

et al. 2024

IJMS

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“…Research has shown that endosomal and cytoplasmic Pattern Recognition Receptors and the cell surface recognize HSV and as such start a cascade of immune response which includes Interferons (IFN), Chemokine, and Cytokine production as well as the recruitment of other inflammatory cells to the location of the infection[ 94 ]. IFN-1 release in acute HSV keratitis limits dendritic lesion enlargement[ 95 ].…”

Section: Understanding the Pathogenesis Of Herpes Simplex Keratitismentioning

confidence: 99%

Herpes simplex keratitis: A brief clinical overview

Musa,

Enaholo,

Aluyi-Osa

et al. 2024

World J Virol

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The aim of our minireview is to provide a brief overview of the diagnosis, clinical aspects, treatment options, management, and current literature available regarding herpes simplex keratitis (HSK). This type of corneal viral infection is caused by the herpes simplex virus (HSV), which can affect several tissues, including the cornea. One significant aspect of HSK is its potential to cause recurrent episodes of inflammation and damage to the cornea. After the initial infection, the HSV can establish a latent infection in the trigeminal ganglion, a nerve cluster near the eye. The virus may remain dormant for extended periods. Periodic reactivation of the virus can occur, leading to recurrent episodes of HSK. Factors triggering reactivation include stress, illness, immunosuppression, or trauma. Recurrent episodes can manifest in different clinical patterns, ranging from mild epithelial involvement to more severe stromal or endothelial disease. The severity and frequency of recurrences vary among individuals. Severe cases of HSK, especially those involving the stroma and leading to scarring, can result in vision impairment or even blindness in extreme cases. The cornea's clarity is crucial for good vision, and scarring can compromise this, potentially leading to visual impairment. The management of HSK involves not only treating acute episodes but also implementing long-term strategies to prevent recurrences and attempt repairs of corneal nerve endings via neurotization. Antiviral medications, such as oral Acyclovir or topical Ganciclovir, may be prescribed for prophylaxis. The immune response to the virus can contribute to corneal damage. Inflammation, caused by the body's attempt to control the infection, may inadvertently harm the corneal tissues. Clinicians should be informed about triggers and advised on measures to minimize the risk of reactivation. In summary, the recurrent nature of HSK underscores the importance of both acute and long-term management strategies to preserve corneal health and maintain optimal visual function.

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“…Various cell types contribute to the innate immune response in both mucosal epithelia and the nervous system, providing additional support and protection during α-HV invasion [8,22,26]. Some of these cells include neutrophils, plasmacytoid dendritic cells (pDCs), and natural killer (NK) cells [27][28][29][30]. These cells play a vital role in the antiviral response partly due to their role in the synthesis and production of cytokines.…”

Section: Basics Of Intrinsic and Innate Immunity Against Alpha Herpes...mentioning

confidence: 99%

Cell Intrinsic Determinants of Alpha Herpesvirus Latency and Pathogenesis in the Nervous System

Salazar,

Luong,

Koyuncu

2023

Viruses

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Alpha herpesvirus infections (α-HVs) are widespread, affecting more than 70% of the adult human population. Typically, the infections start in the mucosal epithelia, from which the viral particles invade the axons of the peripheral nervous system. In the nuclei of the peripheral ganglia, α-HVs establish a lifelong latency and eventually undergo multiple reactivation cycles. Upon reactivation, viral progeny can move into the nerves, back out toward the periphery where they entered the organism, or they can move toward the central nervous system (CNS). This latency–reactivation cycle is remarkably well controlled by the intricate actions of the intrinsic and innate immune responses of the host, and finely counteracted by the viral proteins in an effort to co-exist in the population. If this yin-yang- or Nash-equilibrium-like balance state is broken due to immune suppression or genetic mutations in the host response factors particularly in the CNS, or the presence of other pathogenic stimuli, α-HV reactivations might lead to life-threatening pathologies. In this review, we will summarize the molecular virus–host interactions starting from mucosal epithelia infections leading to the establishment of latency in the PNS and to possible CNS invasion by α-HVs, highlighting the pathologies associated with uncontrolled virus replication in the NS.

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

Cited by 13 publications

References 376 publications

Herpes Simplex Virus ICP27 Protein Inhibits AIM 2-Dependent Inflammasome Influencing Pro-Inflammatory Cytokines Release in Human Pigment Epithelial Cells (hTert-RPE 1)

Herpes Simplex Virus ICP27 Protein Inhibits AIM 2-Dependent Inflammasome Influencing Pro-Inflammatory Cytokines Release in Human Pigment Epithelial Cells (hTert-RPE 1)

Herpes simplex keratitis: A brief clinical overview

Cell Intrinsic Determinants of Alpha Herpesvirus Latency and Pathogenesis in the Nervous System

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