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Microorganisms
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Herpes Simplex Virus (HSV)
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Herpes Simplex Virus (HSV)

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Virology".

Deadline for manuscript submissions: closed (30 November 2023) | Viewed by 9113

Special Issue Editor

Dr. Veijo Hukkanen

E-Mail Website
Guest Editor
Department of Virology, University of Turku, Turku, Finland
Interests: virology; herpesviruses; gene therapy; oncolytic viruses; antivirals; RNA interference

Special Issue Information

Dear Colleagues,

Herpes simplex virus (HSV) is a common pathogen of humans, causing a spectrum of infections ranging from cold sores and genital herpes to serious neonatal herpes infections and encephalitis. However, HSV is also one of the most important oncolytic viruses (destroying cancer cells) and gene therapy vectors. A characteristic feature of HSV is the latent infection in the nervous system, mainly in sensory ganglia. The latent HSV infection is permanent, although recurrences can be treated with antiviral chemotherapy.

For decades, HSV has been considered as a model organism for research on viral gene regulation, virus–host interactions, latent infection, and evasion of antiviral host responses. This Special Issue on “Herpes simplex virus (HSV)” will focus on HSV genetics, HSV genomics and molecular diagnostic methods, pathogenesis of HSV infections, antiviral host responses and viral immune evasion, antiviral therapies, and the application of HSV in cancer therapy.

I cordially invite all colleagues to submit original research, review articles, case reports, and short perspectives pertaining to this important pathogen.

Dr. Veijo Hukkanen
Guest Editor

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. Microorganisms 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

  • herpes simplex virus
  • HSV
  • antiviral
  • gene therapy
  • oncolytic HSV

Published Papers (6 papers)

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Research

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14 pages, 3697 KiB  
Article
Major Virion Tegument Protein VP22 Targets Nuclear Matrix and Chromatin upon Entry into Cells during Productive Herpes Simplex Virus 1 Infection
by Isabella Chi and John A. Blaho
Microorganisms 2024, 12(3), 521; https://doi.org/10.3390/microorganisms12030521 - 5 Mar 2024
Viewed by 702
Abstract
HSV-1 major tegument protein VP22 is present in multiple subcellular locations in the late stages of productive viral infection. We initially performed a detailed time course experiment and observed that VP22 was detected in nuclear and nuclear matrix fractions as early as 4 [...] Read more.
HSV-1 major tegument protein VP22 is present in multiple subcellular locations in the late stages of productive viral infection. We initially performed a detailed time course experiment and observed that VP22 was detected in nuclear and nuclear matrix fractions as early as 4 hpi. The goal was to determine the fate of virion-derived incoming VP22, and we report the following: (i) VP22 was detected in nuclear matrix fractions 1 hpi. (ii) In the presence of cycloheximide (CHX), VP22 was present in the nuclear matrix 1–6 hpi, demonstrating the stability of the protein. (iii) The nuclear matrix targeting of VP22 occurred in infected Vero, HEp-2, and human mammary epithelial (HME) cells and following synchronized infection. Based on these results, we conclude that (iv) VP22 targets the nuclear matrix and chromatin upon entry into cells during productive HSV-1 infection. Full article
(This article belongs to the Special Issue Herpes Simplex Virus (HSV))
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10 pages, 418 KiB  
Article
Atopic Disease as a Risk Factor for Recurrent Herpetic Keratitis
by Margarita Safir and Michael Mimouni
Microorganisms 2024, 12(1), 220; https://doi.org/10.3390/microorganisms12010220 - 21 Jan 2024
Cited by 1 | Viewed by 920
Abstract
Recurrent herpetic keratitis is a leading cause of blindness worldwide. In this population-based cross-sectional study, the medical records of Israeli adolescents and young adults who underwent systematic preconscription evaluation for mandatory military service were reviewed. The prevalence of atopic conjunctival disease was evaluated [...] Read more.
Recurrent herpetic keratitis is a leading cause of blindness worldwide. In this population-based cross-sectional study, the medical records of Israeli adolescents and young adults who underwent systematic preconscription evaluation for mandatory military service were reviewed. The prevalence of atopic conjunctival disease was evaluated in cases with and without documented recurrent herpetic keratitis. The association was tested using uni- and multivariant analyses. Overall, 940,892 adolescents and young adults were included. The mean age was 17.57 ± 1.50 years (range 16–20 years), and 40.70% of participants were female. Recurrent herpetic keratitis was documented in 160 cases, with a prevalence of 0.017% in this age group. Compared to the general population, patients with recurrent herpetic keratitis were significantly more likely to be males (p = 0.003) with a concomitant diagnosis of atopic conjunctival disease (p < 0.0001). Patients with atopic conjunctival disease were 10.60-fold more likely to experience recurrent herpetic keratitis (95% confidence interval (CI): 6.76–16.64, p < 0.0001). Upon multivariate analysis, the results remained significant (p < 0.001). Cases of severe atopic conjunctival disease were more prone to recurrent HSV keratitis compared to mild cases (p < 0.001). These findings suggest that the timely appropriate treatment of atopic conjunctival disease may help reduce the frequency and severity of recurrent HSV keratitis and its complications. Full article
(This article belongs to the Special Issue Herpes Simplex Virus (HSV))
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13 pages, 2058 KiB  
Article
Attenuated Replication-Competent Herpes Simplex Virus Expressing an ECM-Modifying Transgene Hyaluronan Synthase 2 of Naked Mole Rat in Oncolytic Gene Therapy
by Jussi Palomäki, Kiira Kalke, Julius Orpana, Liisa Lund, Fanny Frejborg, Henrik Paavilainen, Hannu Järveläinen and Veijo Hukkanen
Microorganisms 2023, 11(11), 2657; https://doi.org/10.3390/microorganisms11112657 - 29 Oct 2023
Cited by 2 | Viewed by 2046
Abstract
Herpes simplex virus (HSV) has proven successful in treating human cancer. Since the approval of talimogene laherparepvec (T-VEC) in 2015, HSV has been thoroughly researched to discover novel mechanisms to combat cancer and treat other diseases. Another HSV-based drug, beremagene geperpavec (B-VEC), received [...] Read more.
Herpes simplex virus (HSV) has proven successful in treating human cancer. Since the approval of talimogene laherparepvec (T-VEC) in 2015, HSV has been thoroughly researched to discover novel mechanisms to combat cancer and treat other diseases. Another HSV-based drug, beremagene geperpavec (B-VEC), received approval in 2023 to treat the rare genetic disease dystrophic epidermolysis bullosa, and was also the first clinically approved HSV vector carrying an extracellular matrix (ECM)-modifying transgene. The ECM is a network of macromolecules surrounding cells, which provides support and regulates cell growth and differentiation, the disruption of which is common in cancer. The naked mole rat (NMR) has a thick ECM and a unique mutation in the hyaluronan synthase 2 (HAS2) gene, which has been linked to the high cancer resistance of the species. To study the effect of this mutation in human cancer, we have developed an attenuated, replication-competent HSV vector expressing the NMR-HAS2 gene. The viral replication, transgene expression and cytotoxic effect of the novel vector was studied in glioma cells. Our results show that an attenuated, replication-competent HSV vector expressing a foreign ECM-modifying transgene, namely HAS2, provides an effective tool to study and combat cancer in humans. Full article
(This article belongs to the Special Issue Herpes Simplex Virus (HSV))
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11 pages, 774 KiB  
Article
Prevalence of Herpes Simplex and Varicella-Zoster Virus DNA in Corneal Grafts Is Higher than Expected
by Marie Ella Horstmann, Mohammad Al Hariri, Stephanie D. Grabitz, Julia Bing Bu, Melissa Apel, Norbert Pfeiffer and Joanna Wasielica-Poslednik
Microorganisms 2023, 11(10), 2405; https://doi.org/10.3390/microorganisms11102405 - 26 Sep 2023
Cited by 1 | Viewed by 1175
Abstract
Purpose: (1) To determine the prevalence of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), varicella-zoster virus (VZV), and cytomegalovirus (CMV) DNA in donor corneas; (2) To evaluate the clinical outcome of the grafts with viral DNA and to compare donors [...] Read more.
Purpose: (1) To determine the prevalence of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), varicella-zoster virus (VZV), and cytomegalovirus (CMV) DNA in donor corneas; (2) To evaluate the clinical outcome of the grafts with viral DNA and to compare donors with and without viral DNA. Methods: We analyzed data from all donors and recipients who underwent penetrating keratoplasty (PK) or Descemet membrane endothelial keratoplasty (DMEK) between September 2022 and March 2023. Donor corneoscleral rims and excised recipients’ corneal buttons were tested for the presence of HSV-1, HSV-2, VZV, and CMV DNA by polymerase chain reaction (PCR). The results were known 2–3 days after the surgery. We closely followed up on patients whose grafts tested positive for viral DNA. We compared the medical histories of donors with and without viral DNA. Results: We included 85 corneas from 67 donors. Seven (8.2%) donor corneas tested positive for HSV-1 (n = 3) or VZV (n = 4) DNA. We did not detect any HSV-2 or CMV DNA. In the postoperative follow-up of patients with positive PCR, a graft failure was observed in one and infections in two eyes. Re-operation was necessary in three of these cases (42.9%). Patients without herpes DNA in the donor cornea needed reoperation in 7.7% of the cases. Cultural duration, the cause of the donor’s death, and the death-to-explantation interval did not differ significantly between donors with and without viral DNA. Additionally, 3 of the 7 (42.9%) donors with positive PCR were in a septic status at the time of death, compared to 21 of the 78 (26.9%) donors with negative PCR (p = 0.52). Conclusions: The prevalence of herpes DNA in the donor corneas was 8.2% and thus higher than previously reported. We did not notice any evidence for a donor-to-host transmission, but a higher rate of postoperative complications in recipients of the grafts with viral DNA. The donors with and without herpetic DNA did not differ significantly regarding systemic diagnoses or cultural conditions, but sepsis was more frequent in the group with viral DNA. Full article
(This article belongs to the Special Issue Herpes Simplex Virus (HSV))
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18 pages, 3208 KiB  
Article
Herpes Simplex Virus Type 1 Induces AD-like Neurodegeneration Markers in Human Progenitor and Differentiated ReNcell VM Cells
by Blanca Salgado, Isabel Sastre, Maria J. Bullido and Jesus Aldudo
Microorganisms 2023, 11(5), 1205; https://doi.org/10.3390/microorganisms11051205 - 4 May 2023
Cited by 1 | Viewed by 2255
Abstract
An increasing body of evidence strongly suggests that infections or reactivations of herpes simplex virus type 1 (HSV-1) may be closely linked to Alzheimer’s disease (AD). Promising results have been obtained using cell and animal models of HSV-1 infection, contributing to the understanding [...] Read more.
An increasing body of evidence strongly suggests that infections or reactivations of herpes simplex virus type 1 (HSV-1) may be closely linked to Alzheimer’s disease (AD). Promising results have been obtained using cell and animal models of HSV-1 infection, contributing to the understanding of the molecular mechanisms linking HSV-1 infection and AD neurodegeneration. ReNcell VM is a human neural stem cell line that has been used as a model system to study the impact of various infectious agents on the central nervous system. In this study, we demonstrate the suitability of the ReNcell VM cell line for developing a new in vitro model of HSV-1 infection. By following standard differentiation protocols, we were able to derive various nervous cell types, including neurons, astrocytes, and oligodendrocytes, from neural precursors. Additionally, we demonstrated the susceptibility of ReNcell VM cells, including precursor and differentiated cells, to HSV-1 infection and subsequent viral-induced AD-like neurodegeneration. Our findings support the use of this cell line to generate a new research platform for investigating AD neuropathology and its most significant risk factors, which may lead to important discoveries in the context of this highly impactful disease. Full article
(This article belongs to the Special Issue Herpes Simplex Virus (HSV))
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Review

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21 pages, 2267 KiB  
Review
A Revision of Herpes Simplex Virus Type 1 Transcription: First, Repress; Then, Express
by Laura E. M. Dunn, Claire H. Birkenheuer and Joel D. Baines
Microorganisms 2024, 12(2), 262; https://doi.org/10.3390/microorganisms12020262 - 26 Jan 2024
Viewed by 1243
Abstract
The herpes virus genome bears more than 80 strong transcriptional promoters. Upon entry into the host cell nucleus, these genes are transcribed in an orderly manner, producing five immediate–early (IE) gene products, including ICP0, ICP4, and ICP22, while non-IE genes are mostly silent. [...] Read more.
The herpes virus genome bears more than 80 strong transcriptional promoters. Upon entry into the host cell nucleus, these genes are transcribed in an orderly manner, producing five immediate–early (IE) gene products, including ICP0, ICP4, and ICP22, while non-IE genes are mostly silent. The IE gene products are necessary for the transcription of temporal classes following sequentially as early, leaky late, and true late. A recent analysis using precision nuclear run-on followed by deep sequencing (PRO-seq) has revealed an important step preceding all HSV-1 transcription. Specifically, the immediate–early proteins ICP4 and ICP0 enter the cell with the incoming genome to help preclude the nascent antisense, intergenic, and sense transcription of all viral genes. VP16, which is also delivered into the nucleus upon entry, almost immediately reverses this repression on IE genes. The resulting de novo expression of ICP4 and ICP22 further repress antisense, intergenic, and early and late viral gene transcription through different mechanisms before the sequential de-repression of these gene classes later in infection. This early repression, termed transient immediate–early protein-mediated repression (TIEMR), precludes unproductive, antisense, intergenic, and late gene transcription early in infection to ensure the efficient and orderly progression of the viral cascade. Full article
(This article belongs to the Special Issue Herpes Simplex Virus (HSV))
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