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Pathogens
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Viruses and Ocular Infection
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Viruses and Ocular Infection

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Viral Pathogens".

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 12676

Special Issue Editors

Dr. Pawan Kumar Singh

E-Mail Website
Guest Editor
Department of Ophthalmology/Mason Eye Institute, University of Missouri School of Medicine, Columbia, MO 65212, USA
Interests: innate immunity; host-pathogen interaction; ocular infection; inflammation; viruses; glaucoma; gene therapy
Dr. Ashok Kumar

E-Mail Website
Guest Editor
Department of Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine, Detroit, MI 48201, USA
Interests: innate immunity; host-pathogen interaction; ocular infection; inflammation; retina; viruses; endophthalmitis

Special Issue Information

Dear Colleagues,

For the past 15 years, a new infectious disease has been discovered every year, with an outbreak reported on nearly every continent. Many viruses cause lethal infections and transmit via ocular routes that can also cause severe ocular complications. In the current COVID-19 pandemic, many studies have shown that SARS-CoV2 RNA and protein can be detected in the ocular tissues; however, the transmission of this virus via the eye is still debatable. Similarly, flaviviruses, including dengue virus, zika virus, and West Nile virus, are globally distributed and infect up to 400 million people annually and remain the leading cause of global health problems. However, to date, their ocular complications remain underreported. Herpesviruses have been shown to cause lifelong latent infections in neurons, and their reactivation causes vision-impairing conditions known as herpetic stromal keratitis. Likewise, the Ebola virus has been shown to use eyes as a safe haven and cause secondary infections. Looking at viruses and their close association with eyes, it is of utmost importance to investigate and highlight the disease pathobiology, related mechanisms, and novel therapeutics for viral disease to treat ocular and other health-related complications.

In this context, Pathogens will launch a special issue devoted to “Viruses and Ocular Infection”. This Special Issue will focus on all viruses and related ocular diseases and will include both research and review articles covering all aspects of the disease pathobiology, host-pathogen interaction, ocular immunity, and possible therapeutic approaches.  

Dr. Pawan Kumar Singh
Dr. Ashok Kumar
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pathogens is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • ocular infectious disease
  • inflammation
  • ocular viral disease
  • host–pathogen interaction
  • ocular innate immunity
  • blood–retinal barrier

Published Papers (5 papers)

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Research

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12 pages, 6100 KiB  
Article
Prolonged Inflammation and Infectious Changes in the Corneal Epithelium Are Associated with Persistent Epithelial Defect (PED)
by Tanmoy Dutta, Jyoti Sangwan, Moumita Mondal, Mehak Vohra, Vatsala Nidhi, Abha Gour, Neha Kapur, Nidhi Gupta, Tuhin Bhowmick, Arun Chandru, Umang Mathur, Virender Singh Sangwan, Manisha Acharya and Anil Tiwari
Pathogens 2023, 12(2), 261; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens12020261 - 06 Feb 2023
Cited by 2 | Viewed by 1786
Abstract
Purpose: Failure of rapid re-epithelialization within 10–14 days after corneal injury, even with standard supportive treatment, is referred to as persistent corneal epithelial (CE) defect (PED). Though an array of genes regulates reepithelization, their mechanisms are poorly understood. We sought to understand the [...] Read more.
Purpose: Failure of rapid re-epithelialization within 10–14 days after corneal injury, even with standard supportive treatment, is referred to as persistent corneal epithelial (CE) defect (PED). Though an array of genes regulates reepithelization, their mechanisms are poorly understood. We sought to understand the network of genes driving the re-epithelialization in PED. Method: After obtaining informed consent, patients underwent an ophthalmic examination. Epithelial scrapes and tears samples of six PED patients and six individuals (control) undergoing photorefractive keratectomy (PRK) were collected. RNA isolation and quantification were performed using either the epithelial scrape taken from PED patients or from HCLE cells treated with control tears or tears of PED patients. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expression of a few important genes in CE homeostasis, inflammation, and cell–cell communication, viz., Kruppel-like factor 4 (KLF4), GPX4, IL6, TNFα, STING, IL8, desmoglein, and E-cadherin, among others. Their expressions were normalized with their respective housekeeping genes and fold changes were recorded. KLF4 localization and MMPs activity was carried out via immunofluorescence and zymography, respectively. Results: KLF4, a transcription factor important for CE homeostasis, was upregulated in tears-treated HCLE cells and downregulated in PED patients compared to the healthy PRK group. Cell–cell communication genes were also upregulated in tears-treated cells, whereas they were downregulated in the PED tissue group. Genes involved in proinflammation (IL6, 282-fold; TNFα, 43-fold; IL8, 4.2-fold) were highly upregulated in both conditions. MMP9 activity increased upon tears treatment. Conclusions: This study suggests that tears create an acute proinflammatory milieu driving the PED disease pathology, whereas the PED patients scrapes are an indicator of the chronic stage of the disease. Interferons, pro-inflammatory genes, and their pathways are involved in PED, which can be a potential target for inducing epithelialization of the cornea. Full article
(This article belongs to the Special Issue Viruses and Ocular Infection)
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9 pages, 808 KiB  
Article
Ranpirnase (OKG-0301), a Novel Ribonuclease, Demonstrates Antiviral Activity against Adenovirus in the Ad5/NZW Rabbit Ocular Replication Model
by Eric G. Romanowski, Kathleen A. Yates, Eric J. Daniels, Brian M. Strem, John E. Romanowski and Regis P. Kowalski
Pathogens 2022, 11(12), 1485; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens11121485 - 07 Dec 2022
Cited by 1 | Viewed by 1529
Abstract
Adenovirus ocular infections are common ocular viral infections seen worldwide, for which there is no approved antiviral therapy available. Ranpirnase is a novel ribonuclease which preferentially degrades tRNA resulting in an inhibition of protein synthesis. The study goal was to determine the anti-adenoviral [...] Read more.
Adenovirus ocular infections are common ocular viral infections seen worldwide, for which there is no approved antiviral therapy available. Ranpirnase is a novel ribonuclease which preferentially degrades tRNA resulting in an inhibition of protein synthesis. The study goal was to determine the anti-adenoviral activity of topical formulations of ranpirnase (OKG-0301) on adenoviral replication in the Ad5/NZW rabbit ocular replication model. NZW rabbits were inoculated in both eyes with human adenovirus type 5 (HAdV5) after corneal scarification. A day later, topical therapy was initiated in both eyes with 0.03% OKG-0301, 0.003% OKG-0301, saline or 0.5% cidofovir. Eyes were cultured to determine HAdV5 eye titers over 2 weeks. OKG-0301 (0.03% and 0.003%) and 0.5% cidofovir decreased viral titers compared to saline. Furthermore, both OKG-0301 formulations and 0.5% cidofovir shortened the duration of the HAdV5 infection compared to saline. Both 0.03% OKG-0301 and 0.003% OKG-0301 demonstrated increased antiviral activity compared to saline in the Ad5/NZW rabbit ocular replication model. The antiviral activity of the OKG-0301 groups was similar to that of the positive antiviral control, 0.5% cidofovir. Ranpirnase (OKG-0301) may be a potential candidate for a topical antiviral for adenoviral eye infections. Further clinical development is warranted. Full article
(This article belongs to the Special Issue Viruses and Ocular Infection)
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Review

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39 pages, 4465 KiB  
Review
Role of Innate Interferon Responses at the Ocular Surface in Herpes Simplex Virus-1-Induced Herpetic Stromal Keratitis
by Jiayi Ren, Ferrin Antony, Barry T. Rouse and Amol Suryawanshi
Pathogens 2023, 12(3), 437; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens12030437 - 10 Mar 2023
Cited by 6 | Viewed by 3818
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Viruses and Ocular Infection)
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17 pages, 830 KiB  
Review
Neutrophil Extracellular Traps and Their Possible Implications in Ocular Herpes Infection
by Divya Kapoor and Deepak Shukla
Pathogens 2023, 12(2), 209; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens12020209 - 29 Jan 2023
Cited by 3 | Viewed by 2289
Abstract
Neutrophil extracellular traps (NETs) are net-like structures released from neutrophils. NETs predominantly contain cell-free deoxyribonucleic acid (DNA) decorated with histones and neutrophil granule proteins. Numerous extrinsic and intrinsic stimuli can induce the formation of NETs such as pathogens, cytokines, immune complexes, microcrystals, antibodies, [...] Read more.
Neutrophil extracellular traps (NETs) are net-like structures released from neutrophils. NETs predominantly contain cell-free deoxyribonucleic acid (DNA) decorated with histones and neutrophil granule proteins. Numerous extrinsic and intrinsic stimuli can induce the formation of NETs such as pathogens, cytokines, immune complexes, microcrystals, antibodies, and other physiological stimuli. The mechanism of NETosis induction can either be ROS-dependent or independent based on the catalase producing activity of the pathogen. NADPH is the source of ROS production, which in turn depends on the upregulation of Ca2+ production in the cytoplasm. ROS-independent induction of NETosis is regulated through toll-like receptors (TLRs). Besides capturing and eliminating pathogens, NETs also aggravate the inflammatory response and thus act as a double-edged sword. Currently, there are growing reports of NETosis induction during bacterial and fungal ocular infections leading to different pathologies, but there is no direct report suggesting its role during herpes simplex virus (HSV) infection. There are innumerable independent reports showing that the major effectors of NETosis are also directly affected by HSV infection, and thus, there is a strong possibility that HSV interacts with these facilitators that can either result in virally mediated modulation of NETosis or NETosis-mediated suppression of ocular HSV infection. This review focuses on the mechanism of NETs formation during different ocular pathologies, with its prime focus on highlighting their potential implications during HSV ocular infections and acting as prospective targets for the treatment of ocular diseases. Full article
(This article belongs to the Special Issue Viruses and Ocular Infection)
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Other

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16 pages, 1703 KiB  
Systematic Review
Ocular Manifestations of Chikungunya Infection: A Systematic Review
by Liziane Cristine Malaquias da Silva, Fernanda da Silva Platner, Lauany da Silva Fonseca, Virgílio Frota Rossato, Dian Carlos Pereira de Andrade, João de Sousa Valente, Susan Diana Brain and Elizabeth Soares Fernandes
Pathogens 2022, 11(4), 412; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens11040412 - 29 Mar 2022
Cited by 5 | Viewed by 2070
Abstract
The Chikungunya virus (CHIKV) can cause long lasting symptoms and manifestations. However, there is little information on which ocular ones are most frequent following infection. We performed a systematic review (registered in the International Prospective Register of Systematic Reviews; no CRD42020171928) to establish [...] Read more.
The Chikungunya virus (CHIKV) can cause long lasting symptoms and manifestations. However, there is little information on which ocular ones are most frequent following infection. We performed a systematic review (registered in the International Prospective Register of Systematic Reviews; no CRD42020171928) to establish the most frequent ocular manifestations of CHIKV infection and their associations with gender and age. Articles published until September 2020 were selected from PubMed, Scielo, Cochrane and Scopus databases. Only studies with CHIKV-infected patients and eye alterations were included. Reviews, descriptive studies, or those not investigating the human ocular manifestations of CHIKV, those with patients with other diseases and infections, abstracts and studies without relevant data were excluded. Twenty-five studies were selected for inclusion. Their risk of bias was evaluated by a modified Newcastle-Ottawa scale. The most frequent ocular symptoms of CHIKV infection included ocular pain, inflammation and reduced visual acuity, whilst conjunctivitis and optic neuritis were the most common manifestations of the disease. These occurred mostly in individuals of 42 ± 9.5 years of age and woman. The few available reports on CHIKV-induced eye manifestations highlight the need for further research in the field to gather more substantial evidence linking CHIKV infection, the eye and age/gender. Nonetheless, the data emphasizes that ocular alterations are meaningful occurrences of CHIKV infection which can substantially affect quality of life. Full article
(This article belongs to the Special Issue Viruses and Ocular Infection)
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