Herpesviruses and Their Associated Diseases: From Disease Onset to Therapy

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

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 17055

Special Issue Editor


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Guest Editor
Department of Applied Ecology, Faculty of Environmental Sciences, Czech University of Life Sciences Prague, Kamýcká 129, 165 00 Prague, Czech Republic
Interests: infectious diseases; herpesviruses; pharmacology and toxicology; molecular medicine; oncology and hematology; cardiovascular diseases; natural products; drug discovery; analytical and bioanalytical techniques
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Special Issue Information

Dear Colleagues,

Throughout human history, herpesvirus infections remain some of the most significant diseases that threaten human health. During a deep history of coevolution, herpesviruses have formed a fine-tuned equilibrium with their hosts, enabling them to persist and propagate to new hosts. Herpesviruses belong to the family of Herpesviridae, which is a large family of DNA viruses. Herpesviruses are known to infect humans and animals and share the feature of creating lifelong infections in a latent phase with the potential of periodic reactivation. So far, there are eight herpesvirus types known to infect humans, generating serious diseases. These viruses may also affect susceptibility to other infections and disease-producing agents. Recognizing and investigating the factors that affect herpesvirus infection of different cells and tissues will advance to be an area of intensive research. Understanding virus–host interaction will result in new antiviral drugs focused against both viral and cellular targets, and, as virus research has always done, share novel insights into cell biology.

In this Special Issue, we invite the submission of original research papers, communications, reviews, methods articles, and perspectives that cover virus–host interaction in various animal species, including humans. We also welcome research focusing on factors that affect disease development, such as virus–environmental conditions interaction and host–environmental conditions interaction, as well as complications resulting from infections that include herpesvirus-mediated illness complexes in different animal host species. Additionally, papers that provide strategies for future vaccine development and new anti-herpesvirus drugs are also encouraged.

Dr. Sherif T.S. Hassan
Guest Editor

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Keywords

  • Human herpesviruses
  • Animal herpesviruses
  • Isolation and Identification techniques
  • Virus–host interaction
  • Virus–environmental conditions interaction
  • Host–environmental conditions interaction
  • Herpesviruses-associated diseases
  • Vaccine development
  • Anti-herpesvirus drug development
  • Drug resistance

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Published Papers (5 papers)

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Research

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9 pages, 916 KiB  
Article
Incidence of Common Herpesviruses in Colonic Mucosal Biopsies Following Hematopoietic Stem Cell Transplantation
by Oleg V. Goloshchapov, Alexander N. Shvetsov, Alexey B. Chukhlovin, Anna A. Spiridonova, Maria D. Vladovskaya, Ludmila S. Zubarovskaya and Alexander D. Kulagin
Microorganisms 2022, 10(11), 2128; https://doi.org/10.3390/microorganisms10112128 - 27 Oct 2022
Cited by 3 | Viewed by 1777
Abstract
Intestinal complications are common after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, only scarce data concern herpesvirus incidence in the colonic mucosa post-HSCT. Our purpose was to assess the frequency and clinical significance of cytomegalovirus (CMV), Epstein–Barr virus (EBV), human herpesvirus type 6 [...] Read more.
Intestinal complications are common after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, only scarce data concern herpesvirus incidence in the colonic mucosa post-HSCT. Our purpose was to assess the frequency and clinical significance of cytomegalovirus (CMV), Epstein–Barr virus (EBV), human herpesvirus type 6 (HHV6), and herpes simplex virus (HSV) in the colonic mucosa post-HSCT. The study group included 119 patients of different ages, mostly with leukemias and lymphomas, subjected to allo-HSCT from haploidentical related (48%) or HLA-compatible donors (52%). In total, 155 forceps biopsies of the colonic mucosa were taken in cases of severe therapy-resistant intestinal syndrome post-HSCT. Most samples were taken from the descending, sigmoid, and transverse colon. Intestinal GVHD or local infections were assessed clinically and by histology. EBV, CMV, HSV, and HHV6 were tested in colonic mucosal lysates with commercial PCR assays. HSV was found in <8% of colonic samples, along with high HHV6 and CMV positivity (up to 62% and 35%, respectively) and a higher EBV incidence at 5–6 months post-HSCT (35%). For CMV and EBV, significant correlations were revealed between their rates of detection in blood and colonic mucosa (r = 0.489 and r = 0.583; p < 0.05). No significant relationships were found between the presence of herpesviruses and most patients’ characteristics. EBV positivity in colonic samples was correlated with delayed leukocyte and platelet recovery post-HSCT. Higher EBV frequency in the colonic mucosa was found in deceased patients (56% versus 21%, p = 0.02). The correlations among EBV positivity in the colon, lethality rates and delayed hematopoietic reconstitution suggest some relationship with systemic and local EBV reactivation post-transplant. Full article
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11 pages, 1636 KiB  
Article
Ophthalmic Solutions with a Broad Antiviral Action: Evaluation of Their Potential against Ocular Herpetic Infections
by Carla Zannella, Annalisa Chianese, Maddalena De Bernardo, Veronica Folliero, Francesco Petrillo, Anna De Filippis, Giovanni Boccia, Gianluigi Franci, Nicola Rosa and Massimiliano Galdiero
Microorganisms 2022, 10(9), 1728; https://doi.org/10.3390/microorganisms10091728 - 27 Aug 2022
Cited by 3 | Viewed by 1886
Abstract
HSV-1 can be associated with severe and recurrent eye infections characterized by a strong inflammatory response that leads to blepharoconjunctivitis, epithelial and stromal keratitis, and retinal necrosis. The incidence of HSV-1 keratitis is 1.5 million every year worldwide, including more than 40,000 new [...] Read more.
HSV-1 can be associated with severe and recurrent eye infections characterized by a strong inflammatory response that leads to blepharoconjunctivitis, epithelial and stromal keratitis, and retinal necrosis. The incidence of HSV-1 keratitis is 1.5 million every year worldwide, including more than 40,000 new cases exhibiting serious visual failures. Generally, the therapy uses antiviral drugs to promote healing; however, there are currently no compounds that are able to completely eradicate the virus. In addition, the phenomenon of resistance is rapidly spreading among HSV-1 strains, creating mutants developing resistance to the common antiviral drugs; therefore, deep research on this issue is warranted. The efficacy of different ophthalmic solutions already on the market was evaluated for reducing HSV-1 infection. Different plaque assays were set up on epithelial cells, revealing that two ophthalmic solutions were able to inhibit viral replication in the early stages of infection. The data were further confirmed by molecular tests analyzing the expression levels of the principal genes involved in HSV-1 infection, and a strong reduction was observed after only 1 min of eye-drop treatment. Collectively, these results suggested the use of ophthalmic solutions as potential antiviral options for the treatment of ocular herpetic infection. Full article
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16 pages, 2994 KiB  
Article
Potential of Anti-CMV Immunoglobulin Cytotect CP® In Vitro and Ex Vivo in a First-Trimester Placenta Model
by Perrine Coste Mazeau, Chloé Jacquet, Clotilde Muller, Mathis Courant, Chahrazed El Hamel, Thierry Chianea, Sébastien Hantz and Sophie Alain
Microorganisms 2022, 10(4), 694; https://doi.org/10.3390/microorganisms10040694 - 23 Mar 2022
Cited by 4 | Viewed by 2751
Abstract
Background: Congenital CMV infection is the leading cause of neonatal neurological deficit. We herein studied in vitro and ex vivo the potential of the hyperimmune globulin Cytotect CP® (Biotest, Germany) for congenital infection prevention and treatment. Methods: In vitro neutralization assays were [...] Read more.
Background: Congenital CMV infection is the leading cause of neonatal neurological deficit. We herein studied in vitro and ex vivo the potential of the hyperimmune globulin Cytotect CP® (Biotest, Germany) for congenital infection prevention and treatment. Methods: In vitro neutralization assays were conducted in fibroblasts and retinal epithelial cells on the CMV strains TB40/E and VHL/E to determine the 50% and 90% neutralizing doses (ND50 and ND90). The toxicity was assessed by measuring LDH release. Ex vivo assays were conducted in first-trimester villi explants with the TB40/E strain, namely, neutralization assays, the prevention of villi infection, and the inhibition of viral replication in infected villi. Viability was assessed by β-HCG quantification in supernatants. Results: The in vitro neutralization tests showed that Cytotect CP®® inhibits the development of infection foci (DN50: 0.011–0.014 U/mL for VHL/E and 0.032–0.033 U/mL for TB40E) without any toxicity. In the ex vivo neutralization assays, the DN50 were 0.011 U/mL on day 7 and 0.093 U/mL on day 14. For the prevention of villi infection, the EC50 was 0.024 U/mL on day 7. Cytotect-CP® did not inhibit viral growth in infected villi. No impact on villi viability was observed. Conclusions: These results sustained that Cytotect CP® has the potential to prevent CMV congenital infection. Full article
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15 pages, 3194 KiB  
Article
Andrographolide Inhibits Lytic Reactivation of Epstein-Barr Virus by Modulating Transcription Factors in Gastric Cancer
by Praphatson Malat, Tipaya Ekalaksananan, Chukkris Heawchaiyaphum, Supawadee Suebsasana, Sittiruk Roytrakul, Yodying Yingchutrakul and Chamsai Pientong
Microorganisms 2021, 9(12), 2561; https://doi.org/10.3390/microorganisms9122561 - 10 Dec 2021
Cited by 7 | Viewed by 3394
Abstract
Andrographolide is the principal bioactive chemical constituent of Andrographis paniculata and exhibits activity against several viruses, including Epstein–Barr virus (EBV). However, the particular mechanism by which andrographolide exerts an anti-EBV effect in EBV-associated gastric cancer (EBVaGC) cells remains unclear. We investigated the molecular [...] Read more.
Andrographolide is the principal bioactive chemical constituent of Andrographis paniculata and exhibits activity against several viruses, including Epstein–Barr virus (EBV). However, the particular mechanism by which andrographolide exerts an anti-EBV effect in EBV-associated gastric cancer (EBVaGC) cells remains unclear. We investigated the molecular mechanism by which andrographolide inhibits lytic reactivation of EBV in EBVaGC cells (AGS-EBV cell line) using proteomics and bioinformatics approaches. An andrographolide treatment altered EBV protein-expression patterns in AGS-EBV cells by suppressing the expression of EBV lytic protein. Interestingly cellular transcription factors (TFs), activators for EBV lytic reactivation, such as MEF2D and SP1, were significantly abolished in AGS-EBV cells treated with andrographolide and sodium butyrate (NaB) compared with NaB-treated cells. In contrast, the suppressors of EBV lytic reactivation, such as EZH2 and HDAC6, were significantly up-regulated in cells treated with both andrographolide and NaB compared with NaB treatment alone. In addition, bioinformatics predicted that HDAC6 could interact directly with MEF2D and SP1. Furthermore, andrographolide significantly induced cell cytotoxicity and apoptosis of AGS-EBV cells by induction of apoptosis-related protein expression. Our results suggest that andrographolide inhibits EBV lytic reactivation by inhibition of host TFs, partially through the interaction of HDAC6 with TFs, and induces apoptosis of EBVaGC cells. Full article
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Review

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15 pages, 3560 KiB  
Review
Nutraceutical Curcumin with Promising Protection against Herpesvirus Infections and Their Associated Inflammation: Mechanisms and Pathways
by Miroslava Šudomová and Sherif T. S. Hassan
Microorganisms 2021, 9(2), 292; https://doi.org/10.3390/microorganisms9020292 - 31 Jan 2021
Cited by 31 | Viewed by 5908
Abstract
Herpesviruses are DNA viruses that infect humans and animals with the ability to induce latent and lytic infections in their hosts, causing critical health complications. The enrolment of nutraceutical anti-herpesvirus drugs in clinical investigations with promising levels of reduced resistance, free or minimal [...] Read more.
Herpesviruses are DNA viruses that infect humans and animals with the ability to induce latent and lytic infections in their hosts, causing critical health complications. The enrolment of nutraceutical anti-herpesvirus drugs in clinical investigations with promising levels of reduced resistance, free or minimal cellular toxicity, and diverse mechanisms of action might be an effective way to defeat challenges that hurdle the progress of anti-herpesvirus drug development, including the problems with drug resistance and recurrent infections. Therefore, in this review, we aim to hunt down all investigations that feature the curative properties of curcumin, a principal bioactive phenolic compound of the spice turmeric, in regard to various human and animal herpesvirus infections and inflammation connected with these diseases. Curcumin was explored with potent antiherpetic actions against herpes simplex virus type 1 and type 2, human cytomegalovirus, Kaposi’s sarcoma-associated herpesvirus, Epstein–Barr virus, bovine herpesvirus 1, and pseudorabies virus. The mechanisms and pathways by which curcumin inhibits anti-herpesvirus activities by targeting multiple steps in herpesvirus life/infectious cycle are emphasized. Improved strategies to overcome bioavailability challenges that limit its use in clinical practice, along with approaches and new directions to enhance the anti-herpesvirus efficacy of this compound, are also reviewed. According to the reviewed studies, this paper presents curcumin as a promising natural drug for the prevention and treatment of herpesvirus infections and their associated inflammatory diseases. Full article
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