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Keywords = herpes simplex virus type 2

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11 pages, 352 KB  
Article
The Use of CSF Multiplex PCR Panel in Patients with Viral Uveitis
by Young Hwan Jeong, Su Hwan Park, Seung Min Lee, Iksoo Byon, Jongyoun Yi and Sung-Who Park
Diagnostics 2026, 16(1), 143; https://doi.org/10.3390/diagnostics16010143 - 1 Jan 2026
Viewed by 339
Abstract
Background/Objectives: Polymerase chain reaction (PCR) testing of ocular fluids is an essential diagnostic method for identifying infectious causes of uveitis. However, multiplex PCR kits specifically developed for ophthalmic use are not commercially available in many regions, including Korea. Given the biochemical similarity [...] Read more.
Background/Objectives: Polymerase chain reaction (PCR) testing of ocular fluids is an essential diagnostic method for identifying infectious causes of uveitis. However, multiplex PCR kits specifically developed for ophthalmic use are not commercially available in many regions, including Korea. Given the biochemical similarity between cerebrospinal fluid (CSF) and aqueous humor, this study evaluated the diagnostic utility of a commercially available CSF multiplex PCR panel for detecting herpesviruses in patients with suspected viral uveitis. Methods: We retrospectively reviewed the medical records of patients whose aqueous humor samples were analyzed using a multiplex PCR assay originally designed for CSF testing (Seeplex Meningitis-V1 ACE Detection kit, Seegene, Seoul, Republic of Korea). The samples were obtained between May 2019 and June 2023 at two tertiary referral hospitals. The assay targeted herpes simplex virus types 1 and 2 (HSV-1, HSV-2), varicella-zoster virus (VZV), cytomegalovirus (CMV), Epstein–Barr virus (EBV), and human herpesvirus 6 (HHV-6). Patients were classified into three groups: (I) anterior uveitis with suspected herpesviral infection, (II) acute retinal necrosis (ARN), and (III) CMV retinitis. Baseline characteristics, PCR positivity rates, and virus prevalence were compared among the groups. Results: Among 149 eyes tested, 86 were included in the final analysis. The overall positivity rate was 38.4%. PCR positivity was 19.7% (12/61) in Group I, 93.8% (15/16) in Group II, and 66.7% (6/9) in Group III. CMV was the most common pathogen in Groups I (66.7%) and III (100%), while VZV was predominant in Group II (80%). No HHV-6 infection was detected. Conclusions: The positivity rate in anterior uveitis (Group I) was lower than previously reported, likely due to the limited sample volume relative to the assay’s requirement. Nevertheless, the assay demonstrated diagnostic reliability comparable to previous reports for ARN and CMV retinitis. Therefore, the CSF-based multiplex PCR panel serves as a feasible and cost-effective diagnostic option for sight-threatening posterior segment infections, facilitating prompt diagnosis and treatment, although further optimization is warranted for anterior uveitis. Full article
(This article belongs to the Special Issue Innovative Diagnostic Approaches in Retinal Diseases)
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12 pages, 1060 KB  
Article
Epidemiological Characteristics of HSV-1 and HSV-2 in 177,599 Patients Based on PCR Testing in South Korea (2018–2022)
by Hyeong Ho Kim, Sung Hun Jang, Jeong Su Han, Jae-Sik Jeon and Jae Kyung Kim
Pathogens 2025, 14(11), 1107; https://doi.org/10.3390/pathogens14111107 - 30 Oct 2025
Viewed by 2670
Abstract
HSV-1 is associated with oral lesions and non-sexual transmission; HSV-2 is primarily transmitted through sexual contact and causes genital infections. Understanding the epidemiological dynamics of both viruses is essential for guiding targeted public-health responses. We conducted a retrospective analysis of 177,599 clinical specimens [...] Read more.
HSV-1 is associated with oral lesions and non-sexual transmission; HSV-2 is primarily transmitted through sexual contact and causes genital infections. Understanding the epidemiological dynamics of both viruses is essential for guiding targeted public-health responses. We conducted a retrospective analysis of 177,599 clinical specimens collected between September 2018 and December 2022 from patients with symptoms suggestive of sexually transmitted infections (STIs) at healthcare institutions across South Korea. HSV-1 and HSV-2 were identified using a real-time PCR assay; positivity rates were stratified by age, sex, specimen type, and year of testing. The overall positivity rate was 0.26% for HSV-1 and 1.60% for HSV-2. HSV-1 was most prevalent among individuals aged <19 years; HSV-2 showed the highest positivity in females aged 20–29 years, declining with age thereafter. HSV-2 positivity was significantly higher in females than in males. A significant decline in HSV-2 positivity was observed over the 5-year study period, while HSV-1 positivity remained stable. This nationwide PCR-based study reveals distinct age- and sex-related epidemiological patterns of HSV-1 and HSV-2. The findings support the need for age-specific and gender-specific STI screening strategies and health education programs. The declining trend in HSV-2 infection may reflect the impact of recent public-health initiatives. Full article
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30 pages, 3105 KB  
Article
Sumac Polyphenols as Pan-Herpesvirus Inhibitors
by Shavkat I. Salikhov, Yuliya I. Oshchepkova, Jamolitdin F. Ziyavitdinov, Jamshid M. Ashurov, Nodir S. Berdiev, Mikhail S. Kolundin, Akhmed O. Gaidarov, Ali S. Turgiev, Kirill I. Yurlov, Victor F. Larichev, Irina T. Fedyakina, Valeria L. Andronova, Natalia E. Fedorova, Alla A. Kushch, Alexander V. Ivanov and Eduard V. Karamov
Int. J. Mol. Sci. 2025, 26(21), 10398; https://doi.org/10.3390/ijms262110398 - 26 Oct 2025
Viewed by 1032
Abstract
Pandemic preparedness is a complex of threat-agnostic countermeasures developed in advance which would be efficient against a future outbreak regardless of its causative agent, and broad-spectrum antivirals constitute a critical component of this complex. Plant polyphenols are known to suppress viruses of unrelated [...] Read more.
Pandemic preparedness is a complex of threat-agnostic countermeasures developed in advance which would be efficient against a future outbreak regardless of its causative agent, and broad-spectrum antivirals constitute a critical component of this complex. Plant polyphenols are known to suppress viruses of unrelated families by acting on multiple viral and cellular structures. We therefore searched for broad-spectrum antivirals among polyphenols that have been confirmed as safe to humans. The ellagitannin geraniin and galloylglucose constituents of the drug Rutan (1,2,3,4,6-penta-O-galloyl-β-D-glucose [R5], 3-bis-O-galloyl-1,2,4,6-tetra-O-galloyl-β-D-glucose [R6], 2,4-bis-O-galloyl-1,3,6-tri-O-galloyl-β-D-glucose [R7], 2,3,4-bis-O-galloyl-1,6-di-O-galloyl-β-D-glucose [R8]) were isolated from Geranium sanguineum and sumac (Rhus coriaria), respectively. We revealed their activity towards herpes simplex viruses (HSV-1 and HSV-2), human cytomegalovirus (CMV), and the Epstein–Barr virus (EBV). R5 suppressed HSV-1 and HSV-2 with equal efficiency, while Rutan and R7 were more active against HSV-1, and geraniin against HSV-2. Rutan and R5 also inhibited the intracellular replication of CMV and EBV (contrary to our expectations, geraniin and polyphenols R6–R8 showed no activity). Thus, we have shown for the first time that sumac polyphenols are capable of suppressing—in addition to HIV, influenza virus, and SARS-CoV-2—the reproduction of representatives of all three Orthoherpesviridae subfamilies, meeting the criteria for further development as broad-spectrum antivirals. Full article
(This article belongs to the Special Issue Molecular View of Natural Products with Antiviral Effects)
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41 pages, 9253 KB  
Review
The Path Towards Effective Long-Lasting Tissue-Targeted Prime/Pull/Keep Herpes Simplex Therapeutic Vaccines
by Afshana Quadiri, Yassir Lekbach, Elhoucine Elfatimi, Swayam Prakash, Hawa Vahed, Sweta Karan, Azizur Rehman, Sarah Xue Le Ng, Chhaya Maurya, Reilly Chow and Lbachir BenMohamed
Vaccines 2025, 13(9), 908; https://doi.org/10.3390/vaccines13090908 - 27 Aug 2025
Cited by 3 | Viewed by 8516
Abstract
The development of vaccines against many infectious diseases has been a great success of medical science over the last century. However, despite numerous efforts, effective vaccines for herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) remain elusive. Since 1920s, a range [...] Read more.
The development of vaccines against many infectious diseases has been a great success of medical science over the last century. However, despite numerous efforts, effective vaccines for herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) remain elusive. Since 1920s, a range of therapeutic vaccine candidates, primarily focusing on neutralizing antibodies, have failed to confer robust and durable protective immunity against recurrent herpes. Recent advances in omics, artificial intelligence, and deep learning have opened new horizons for the rational design of tissue-targeted herpes vaccine strategies for inducing potent and durable HSV-specific CD4+ and CD8+ TRM cell immunity at both the sensory ganglia (central immunity), the site of latency/reactivation cycle, and the mucocutaneous epithelial tissues (peripheral immunity), the site of viral replication that causes herpetic lesions. Prime/Pull/Keep ocular and genital herpes vaccine candidates (PPK vaccines) have recently shown success in pre-clinical animal model trials of recurrent ocular and genital herpes. These PPK vaccines used “asymptomatic” epitopes/antigens to prime CD4+ and CD8+ T cells (Prime); primed T cells are then pulled towards the infected central and peripheral epithelial tissues using T cell-attracting chemokines, such as CXCL11 (Pull), followed by survival cytokines (IL-2, IL-7 and/or IL-15) or mucosal chemokines (CXCL17 and/or CCL28) to maintain the “pulled” tissue-resident T cells longer within infected tissues (Keep). We discuss recent efforts in designing a clinically adapted, all-in-one PPK mucosal therapeutic vaccine that would require a single administration to sequentially trigger all three PPK steps of priming, recruiting, and maintaining antiviral, tissue-resident, protective T cells at the primary sites of viral entry and latency. Full article
(This article belongs to the Special Issue Herpes Simplex Virus Infection, Immunity, and Vaccine Development)
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14 pages, 15805 KB  
Article
Herpes Simplex 2 Virus Depletes Cells of DEAD-Box Helicase 3 Protein by Packaging It into Virions
by Carmen Rita Piazza, Giulia Lottini, Paola Quaranta, Paola Perrera, Fabio Filippini, Michele Lai, Cristina Di Primio, Giulia Freer and Mauro Pistello
Viruses 2025, 17(8), 1124; https://doi.org/10.3390/v17081124 - 15 Aug 2025
Viewed by 1230
Abstract
Human DEAD-box helicase 3 (DDX3) is a multifunctional RNA helicase implicated in mRNA unwinding and the regulation of gene expression. While DDX3 has been extensively studied in the context of RNA virus replication, its role in DNA virus replication remains less understood. In [...] Read more.
Human DEAD-box helicase 3 (DDX3) is a multifunctional RNA helicase implicated in mRNA unwinding and the regulation of gene expression. While DDX3 has been extensively studied in the context of RNA virus replication, its role in DNA virus replication remains less understood. In this study, we explore the involvement of DDX3 in the life cycle of Herpes Simplex Virus type 2 (HSV-2), a double-stranded DNA virus. Silencing of DDX3 expression with siRNA significantly impaired HSV-2 replication, indicating that DDX3 supports viral propagation. Unexpectedly, HSV-2 infection led to a marked reduction in cellular DDX3 protein levels during in vitro replication in human cells, particularly at 24 h post-infection, corresponding to the peak of viral production. Notably, this decrease was not accompanied by a reduction in DDX3 mRNA levels, nor was it prevented by proteasome inhibition, suggesting an alternative mechanism of DDX3 depletion. Further analysis revealed substantial amounts of DDX3 protein within HSV-2 virions, supporting the hypothesis that DDX3 is packaged into viral particles during replication. We propose that HSV-2 exploits host DDX3 by incorporating it into progeny virions to facilitate early stages of infection in newly infected cells. However, no evidence linking DDX3 to the assembly process of HSV-2 particles was found. These findings expand the known functional repertoire of DDX3 and highlight its potential as a host factor co-opted by DNA viruses, suggesting a broader relevance in antiviral strategies. Full article
(This article belongs to the Section Animal Viruses)
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23 pages, 3795 KB  
Article
Exploring Gene Expression Changes in Murine Female Genital Tract Tissues Following Single and Co-Infection with Nippostrongylus brasiliensis and Herpes Simplex Virus Type 2
by Roxanne Pillay, Pragalathan Naidoo and Zilungile L. Mkhize-Kwitshana
Pathogens 2025, 14(8), 795; https://doi.org/10.3390/pathogens14080795 - 8 Aug 2025
Viewed by 1282
Abstract
Background and Aim: The immunological interactions between soil-transmitted helminths (STHs) and herpes simplex virus type 2 (HSV-2), particularly in the context of co-infection, are poorly understood. Next-generation sequencing (NGS) offers a powerful approach to explore these complex immune responses and uncover potential therapeutic [...] Read more.
Background and Aim: The immunological interactions between soil-transmitted helminths (STHs) and herpes simplex virus type 2 (HSV-2), particularly in the context of co-infection, are poorly understood. Next-generation sequencing (NGS) offers a powerful approach to explore these complex immune responses and uncover potential therapeutic targets. This study leveraged NGS and bioinformatic tools to investigate transcriptional changes and immunological pathways in female genital tract (FGT) tissues of BALB/c mice acutely infected with Nippostrongylus brasiliensis (Nb), HSV-2, or co-infected. Methods: Total RNA was harvested from FGT tissues of BALB/c mice infected with Nb, HSV-2, co-infected with both pathogens, and uninfected controls. Differentially expressed genes (DEGs) were identified by comparing uninfected versus infected FGT tissues in R using edgeR and limma packages. Immune-related genes were identified by intersecting DEGs in each group-wise comparison with immune function gene sets derived from the Mouse Genome Informatics (MGI) database. Functional and pathway enrichment analyses were performed with g: Profiler and protein–protein interaction networks were built using the STRING database and visualized with Cytoscape. Key hub genes and significant gene modules were identified using the Cytoscape plugins CytoHubba and MCODE, followed by further functional analysis of these modules. Results: NGS analysis revealed distinct gene expression profiles in response to single infection with Nb or HSV-2, with both showing significant differences when uninfected controls were compared to infected FGT tissues at a 5% false discovery rate. Notably, there were no significant differences in gene expression profiles between uninfected and co-infected FGT tissues. In the comparison of uninfected versus Nb-infected FGT tissues, 368 DEGs were identified, with 356 genes upregulated and 12 downregulated. Several immune-related genes, such as Ptprc, Ccl11, Ccr2, and Cx3cr1, were significantly altered. Pathway analysis of DEGs, hub genes, and significant modules indicated modulation of immune and defense responses. Notably, Nb infection induced a robust Th2-dominant immune response in the FGT, with downregulation of pro-inflammatory genes. This likely reflects helminth-driven modulation that may impair protective Th1 responses and highlights the systemic impact of Nb on the FGT immunity. In the comparison of uninfected versus HSV-2-infected FGT tissues, 140 DEGs were identified, with 121 upregulated and 19 downregulated. Immune-related genes, including Ldlr, Camk1d, Lrp8 and Epg5, were notably altered. HSV-2 infection led to early and predominant downregulation of immune genes, consistent with viral immune evasion strategies. In addition, functional analysis revealed enrichment in cell cycle and sterol biosynthesis pathways, suggesting that HSV-2 modulates host metabolism to support viral replication while influencing immune responses. In co-infection, no significant transcriptional changes were observed, potentially reflecting immune antagonism where Nb-induced Th2 responses may suppress HSV-2-driven Th1 immune responses. Conclusions: This preliminary study offers insights into the gene expression responses in the FGT to acute single and co-infection with Nb and HSV-2. Together, these findings reveal distinct transcriptomic changes in the FGT following Nb and HSV-2 infection, with co-infection potentially leading to immune antagonism and transcriptional equilibrium. This highlights the complex interplay between helminth- and virus-induced immune modulation in shaping FGT immunity. By leveraging NGS, this study highlights important immune-related pathways and serves as a foundation for further investigations into the mechanistic roles of DEGs in immunity to these pathogens, with potential implications for developing novel therapeutic strategies. Full article
(This article belongs to the Special Issue Immunity and Immunoregulation in Helminth Infections)
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28 pages, 2482 KB  
Article
Characterization of microRNA Expression Profiles of Murine Female Genital Tracts Following Nippostrongylus brasiliensis and Herpes Simplex Virus Type 2 Co-Infection
by Roxanne Pillay, Pragalathan Naidoo and Zilungile L. Mkhize-Kwitshana
Microorganisms 2025, 13(8), 1734; https://doi.org/10.3390/microorganisms13081734 - 24 Jul 2025
Viewed by 1309
Abstract
Soil-transmitted helminths (STHs) and Herpes Simplex Virus type 2 (HSV-2) are highly prevalent infections with overlapping distribution, particularly in resource-poor regions. STH/HSV-2 co-infections may impact female reproductive health. However, many aspects of STH/HSV-2 co-infections, including the role of microRNAs (miRNAs) in regulating female [...] Read more.
Soil-transmitted helminths (STHs) and Herpes Simplex Virus type 2 (HSV-2) are highly prevalent infections with overlapping distribution, particularly in resource-poor regions. STH/HSV-2 co-infections may impact female reproductive health. However, many aspects of STH/HSV-2 co-infections, including the role of microRNAs (miRNAs) in regulating female genital tract (FGT) immunity and their potential contribution to pathologies such as chronic inflammation, impaired mucosal defense, and reproductive tract cancers remain unclear. In this study we investigated the miRNA expression profiles in murine FGT tissues following single or co-infection with Nippostrongylus brasiliensis (Nb) and HSV-2 and explored predicted miRNA-mRNA targets and pathways. An analysis of miRNA sequencing data was conducted to determine differentially expressed (DE) miRNAs between infected FGT tissues and uninfected controls. Ingenuity Pathway Analysis was conducted to predict the immune-related target genes of the DE miRNAs and reveal enriched canonical pathways, top diseases, and biological functions. Selected representative DE miRNAs were validated using RT-qPCR. Our results showed a total of eight DE miRNAs (mmu-miR-218-5p, mmu-miR-449a-5p, mmu-miR-497a-3p, mmu-miR-144-3p, mmu-miR-33-5p, mmu-miR-451a, mmu-miR-194-5p, and mmu-miR-192-5p) in the comparison of Nb-infected versus uninfected controls; nine DE miRNAs (mmu-miR-451a, mmu-miR-449a-5p, mmu-miR-144-3p, mmu-miR-376a-3p, mmu-miR-192-5p, mmu-miR-218-5p, mmu-miR-205-3p, mmu-miR-103-3p, and mmu-miR-200b-3p) in the comparison of HSV-2-infected versus uninfected controls; and one DE miRNA (mmu-miR-199a-5p) in the comparison of Nb/HSV-2 co-infected versus uninfected controls (p-value < 0.05, |logFC| ≥ 1). Core expression analysis showed that, among other canonical pathways, the DE miRNAs and their predicted mRNA targets were involved in neutrophil degranulation, interleukin-4 and interleukin-13 signaling, natural killer cell signaling, interferon alpha/beta signaling, and ISGylation. Additionally, cancer was predicted as one of the significantly enriched diseases, particularly in the co-infected group. This is the first study to provide insights into the FGT miRNA profiles following Nb and HSV-2 single and co-infection, as well as the predicted genes and pathways they regulate, which may influence host immunity and pathology. This study highlights the role of miRNAs in regulating FGT immunity and pathology in the context of STH/HSV-2 co-infection. Full article
(This article belongs to the Special Issue Insights into Microbial Infections, Co-Infections, and Comorbidities)
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16 pages, 871 KB  
Article
Primary HSV-2 Infection in an Immunocompromised Patient Reveals High Diversity of Drug-Resistance Mutations in the Viral DNA Polymerase
by Hanna Helena Schalkwijk, Sarah Gillemot, Emilie Frobert, Florence Morfin, Sophie Ducastelle, Anne Conrad, Pierre Fiten, Ghislain Opdenakker, Robert Snoeck and Graciela Andrei
Viruses 2025, 17(7), 962; https://doi.org/10.3390/v17070962 - 9 Jul 2025
Viewed by 1788
Abstract
Herpes simplex virus 2 (HSV-2) remains a significant cause of morbidity and mortality in immunocompromised individuals, despite the availability of effective antivirals. Infections caused by drug-resistant isolates are an emerging concern among these patients. Understanding evolutionary aspects of HSV-2 resistance is crucial for [...] Read more.
Herpes simplex virus 2 (HSV-2) remains a significant cause of morbidity and mortality in immunocompromised individuals, despite the availability of effective antivirals. Infections caused by drug-resistant isolates are an emerging concern among these patients. Understanding evolutionary aspects of HSV-2 resistance is crucial for designing improved therapeutic strategies. Here, we characterized 11 HSV-2 isolates recovered from various body sites of a single immunocompromised patient suffering from a primary HSV-2 infection unresponsive to acyclovir and foscarnet. The isolates were analyzed phenotypically and genotypically (Sanger sequencing of viral thymidine kinase and DNA polymerase genes). Viral clone isolations, deep sequencing, viral growth kinetics, and dual infection competition assays were performed retrospectively to assess viral heterogeneity and fitness. Sanger sequencing identified mixed populations of DNA polymerase mutant variants. Viral clones were plaque-purified and genotyped, revealing 17 DNA polymerase mutations (K533E, A606V, C625R, R628C, A724V, S725G, S729N, I731F, Q732R, M789T/K, Y823C, V842M, R847C, F923L, T934A, and R964H) associated with acyclovir and foscarnet resistance. Deep-sequencing of the DNA polymerase detected drug-resistant variants ranging between 1 and 95%, although the first two isolates had a wild-type DNA polymerase. Some mutants showed reduced fitness, evidenced by (i) the frequency of variants identified by deep-sequencing not correlating with the proportion of mutants found by plaque-purification, (ii) loss of the variants upon passaging in cell culture, or (iii) reduced frequencies in competition assays. This study reveals the rapid evolution of heterogeneous drug-resistant HSV-2 populations under antiviral therapy, highlighting the need for alternative treatment options and resistance surveillance, especially in severe infections. Full article
(This article belongs to the Special Issue Mechanisms of Herpesvirus Resistance)
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46 pages, 1675 KB  
Review
Human Papillomavirus and Other Relevant Issues in Cervical Cancer Pathogenesis
by Amitabha Ray
Int. J. Mol. Sci. 2025, 26(12), 5549; https://doi.org/10.3390/ijms26125549 - 10 Jun 2025
Cited by 4 | Viewed by 5791
Abstract
Cancer of the uterine cervix (cervical cancer) is a leading cancer among women worldwide, although its incidence has been reducing in many developing nations. In the majority of cervical cancer cases, the presence of high-risk human papillomavirus (HPV) is usually detected. However, a [...] Read more.
Cancer of the uterine cervix (cervical cancer) is a leading cancer among women worldwide, although its incidence has been reducing in many developing nations. In the majority of cervical cancer cases, the presence of high-risk human papillomavirus (HPV) is usually detected. However, a growing body of evidence currently considers that exclusive HPV infection may not be sufficient for cancer development. Apart from certain common risk factors for cervical cancer, like poor nutritional status and smoking, many studies documented an association with other viral infections, such as human immunodeficiency virus (HIV) and herpes simplex virus type 2 (HSV-2). Similarly, vaginal bacterial populations perhaps play a key role in cervical cancer. It may be worth mentioning that different bacterial species can immensely influence (either protecting or adversely) the biochemical characteristics of the cervicovaginal environment—for example, Lactobacillus crispatus, Gardnerella vaginalis, and Chlamydia trachomatis. As a result, chronic infections with unfavorable microorganisms (other than HPV) may affect the pathological processes of malignancy. On the other hand, the cervix is an estrogen-sensitive organ like the corpus uteri (i.e., the body of the uterus). Estrogen and different estrogen receptors are implicated in the development and promotion of various cancers, including endometrial cancer. A number of reports also suggest a close association between estrogen and HPV in the development of cervical cancer. Furthermore, estrogen is linked with the characteristics of the vaginal microenvironment including bacteria. Therefore, several of the abovementioned factors (some are preventable) could play an important role in the progression of cervical neoplastic lesions. Full article
(This article belongs to the Section Molecular Oncology)
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27 pages, 1879 KB  
Article
Syndemic Synergy of HPV, HIV, and HSV-2 for Oncogenic HPV Replication in Female Sex Workers
by Jonathan Muwonga Tukisadila, Ralph-Sydney Mboumba Bouassa, Serge Tonen-Wolyec, Hugues Loemba, Jeremie Muwonga and Laurent Belec
Trop. Med. Infect. Dis. 2025, 10(6), 157; https://doi.org/10.3390/tropicalmed10060157 - 7 Jun 2025
Cited by 2 | Viewed by 2419
Abstract
Background: Female sex workers (FSWs) in sub-Saharan Africa bear a disproportionate burden of sexually transmitted infections, including HIV, high-risk HPV (HR-HPV), and herpes simplex virus type 2 (HSV-2). This study evaluated possible association between HR-HPV, HIV, and HSV-2 among FSWs in the Democratic [...] Read more.
Background: Female sex workers (FSWs) in sub-Saharan Africa bear a disproportionate burden of sexually transmitted infections, including HIV, high-risk HPV (HR-HPV), and herpes simplex virus type 2 (HSV-2). This study evaluated possible association between HR-HPV, HIV, and HSV-2 among FSWs in the Democratic Republic of the Congo. Methods: A cross-sectional study was conducted among 432 FSWs (mean age, 28.1 years) recruited via respondent-driven sampling. Genital self-sampling using the V-Veil UP2™ device was performed, followed by HPV genotyping and quantification by multiplex PCR, and HSV-2 DNA detection by PCR. Results: Among 415 participants, HR-HPV prevalence was 36.9%, with HPV-52 (14.9%), HPV-58 (10.1%), and HPV-16 (6.5%) as leading genotypes. Overall, 89% of HR-HPV-positive women harbored genotypes covered by Gardasil-9®. Co-infection with HIV and HSV-2 significantly increased HPV prevalence, genotype diversity, and viral load. Notably, HSV-2 positivity was the sole independent predictor of elevated replication of HR-HPV (p < 0.001), vaccine HR-HPV (p < 0.001), and non-vaccine HR-HPV (p < 0.021). Conclusions: FSWs exhibit a high burden of HR-HPV, shaped by co-infections with HIV and HSV-2. HSV-2 independently drives HR-HPV replication, highlighting its role in HPV persistence and cervical cancer risk. Integrated HSV-2 detection and Gardasil-9® vaccination should be prioritized in cervical cancer elimination strategies targeting high-risk populations in sub-Saharan Africa. Full article
(This article belongs to the Special Issue HIV Testing, Prevention and Care Interventions, 2nd Edition)
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18 pages, 2033 KB  
Article
Imiquimod, a Promising Broad-Spectrum Antiviral, Prevents SARS-CoV-2 and Canine Coronavirus Multiplication Through the MAPK/ERK Signaling Pathway
by Josefina Vicente, Freddy Armando Peñaranda Figueredo, Stefania Mantovani, Daniela Laura Papademetrio, Sergio Ivan Nemirovsky, Andrea Alejandra Barquero, Carina Shayo and Carlos Alberto Bueno
Viruses 2025, 17(6), 801; https://doi.org/10.3390/v17060801 - 31 May 2025
Viewed by 1859
Abstract
Respiratory viruses can cause life-threatening conditions such as sepsis and acute respiratory distress syndrome. However, vaccines and effective antivirals are available for only a limited number of infections. The majority of approved antivirals are direct-acting agents, which target viral proteins essential for infection. [...] Read more.
Respiratory viruses can cause life-threatening conditions such as sepsis and acute respiratory distress syndrome. However, vaccines and effective antivirals are available for only a limited number of infections. The majority of approved antivirals are direct-acting agents, which target viral proteins essential for infection. Unfortunately, mutations have already emerged that confer resistance to these antivirals. In addition, there is an urgent need for broad-spectrum antivirals to address the unpredictable emergence of new viruses with pandemic potential. One promising strategy involves modulating the innate immune response and cellular signaling. Imiquimod, a Toll-like receptor 7 (TLR7) agonist, has shown efficacy in murine models of influenza and respiratory syncytial virus (RSV). Additionally, it demonstrates antiviral activity against herpes simplex virus type 1 (HSV-1) and RSV independent of the TLR7/nuclear factor kappa B (NF-κB) pathway, with protein kinase A (PKA) as a crucial downstream effector. In this study, we demonstrate that imiquimod exhibits concentration-dependent antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and canine coronavirus (CCoV) in epithelial cells, underscoring its broad-spectrum action against coronaviruses. Moreover, its anti-coronavirus effect appears to be independent of the TLR/NF-κB and PKA/exchange protein directly activated by cyclic adenosine monophosphate (EPAC) pathways and may instead be linked to the activation of the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway. The ability of imiquimod to inhibit coronavirus replication via the MEK/ERK pathway, coupled with its immunomodulatory properties, highlights its potential as a broad-spectrum antiviral. Full article
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20 pages, 1275 KB  
Article
Bioprospecting Marine Fungi from the Plastisphere: Osteogenic and Antiviral Activities of Fungal Extracts
by Matteo Florio Furno, Vincent Laizé, Irene Arduino, Giang Nam Pham, Federica Spina, Mohamed Mehiri, David Lembo, Paulo J. Gavaia and Giovanna Cristina Varese
Mar. Drugs 2025, 23(3), 115; https://doi.org/10.3390/md23030115 - 7 Mar 2025
Cited by 3 | Viewed by 2216
Abstract
Marine microplastics (MPs) represent a novel ecological niche, populated by fungi with high potential for pharmaceutical discovery. This study explores the bioactivity of fungal strains isolated from MPs in Mediterranean sediments, focusing on their osteogenic and antiviral activities. Crude extracts prepared via solid-state [...] Read more.
Marine microplastics (MPs) represent a novel ecological niche, populated by fungi with high potential for pharmaceutical discovery. This study explores the bioactivity of fungal strains isolated from MPs in Mediterranean sediments, focusing on their osteogenic and antiviral activities. Crude extracts prepared via solid-state and submerged-state fermentation were tested for their effects on extracellular matrix mineralization in vitro and bone growth in zebrafish larvae, and for their activity against the respiratory syncytial virus (RSV) and herpes simplex virus type 2 (HSV-2). Several extracts exhibited significant mineralogenic and osteogenic activities, with Aspergillus jensenii MUT6581 and Cladosporium halotolerans MUT6558 being the most performing ones. Antiviral assays identified extracts from A. jensenii MUT6581 and Bjerkandera adusta MUT6589 as effective against RSV and HSV-2 at different extents, with no cytotoxic effect. Although chemical profiling of A. jensenii MUT6581 extract led to the isolation of decumbenones A and B, they did not reproduce the observed bioactivities, suggesting the involvement of other active compounds or synergistic effects. These results highlight the plastisphere as a valuable resource for novel bioactive compounds and suggest the need for further fractionation and characterization to identify the molecules responsible for these promising activities. Full article
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10 pages, 4613 KB  
Case Report
Late-Onset HSV-2 Encephalitis in a Kidney Transplant Recipient: A Rare Case Report
by Danijela Zjačić Puljiz, Ivana Vrkić, Ivo Jeličić, Dijana Borić Škaro, Ivana Kristina Delić Jukić, Lučana Vicelić Čutura and Mirela Pavičić Ivelja
Life 2025, 15(2), 152; https://doi.org/10.3390/life15020152 - 22 Jan 2025
Viewed by 1637
Abstract
Infections are an important cause of morbidity and mortality in renal transplant recipients. Among the viral pathogens encountered in this population, herpes simplex virus (HSV), a member of the Alphaherpesvirinae subfamily, has an important place. HSV type 2 infections in this immunosuppressed population [...] Read more.
Infections are an important cause of morbidity and mortality in renal transplant recipients. Among the viral pathogens encountered in this population, herpes simplex virus (HSV), a member of the Alphaherpesvirinae subfamily, has an important place. HSV type 2 infections in this immunosuppressed population are primarily due to viral reactivation. While HSV-2 frequently presents as genital herpes or remains asymptomatic, in rare cases, it can lead to severe neurological manifestations, such as encephalitis, particularly in the early post-transplant period with a reported mortality rate of up to 40%. We present the case of a 49-year-old male who, three years after kidney transplantation, developed acute neurological symptoms, including aphasia and disorientation. Polymerase chain reaction (PCR) analysis of cerebrospinal fluid (CSF) identified HSV-2 as the causative pathogen, enabling a swift and accurate diagnosis. The patient was promptly treated with intravenous acyclovir, adjusted for renal function, resulting in complete neurological recovery and subsequent negative follow-up CSF PCR results. This case emphasizes the vital role of PCR diagnostics as the gold standard for confirming viral encephalitis, particularly in immunosuppressed patients, where atypical presentations can complicate diagnosis. It also highlights the importance of considering HSV-2 encephalitis in the differential diagnosis even beyond the immediate post-transplant period. Early recognition and management, facilitated by the multidisciplinary approach, are critical for improving outcomes in this vulnerable patient population. Full article
(This article belongs to the Special Issue Encephalitis: From Molecular Pathophysiology to Therapy)
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32 pages, 1321 KB  
Review
Shattering the Amyloid Illusion: The Microbial Enigma of Alzheimer’s Disease Pathogenesis—From Gut Microbiota and Viruses to Brain Biofilms
by Anna Onisiforou, Eleftheria G. Charalambous and Panos Zanos
Microorganisms 2025, 13(1), 90; https://doi.org/10.3390/microorganisms13010090 - 5 Jan 2025
Cited by 15 | Viewed by 8282
Abstract
For decades, Alzheimer’s Disease (AD) research has focused on the amyloid cascade hypothesis, which identifies amyloid-beta (Aβ) as the primary driver of the disease. However, the consistent failure of Aβ-targeted therapies to demonstrate efficacy, coupled with significant safety concerns, underscores the need to [...] Read more.
For decades, Alzheimer’s Disease (AD) research has focused on the amyloid cascade hypothesis, which identifies amyloid-beta (Aβ) as the primary driver of the disease. However, the consistent failure of Aβ-targeted therapies to demonstrate efficacy, coupled with significant safety concerns, underscores the need to rethink our approach to AD treatment. Emerging evidence points to microbial infections as environmental factors in AD pathoetiology. Although a definitive causal link remains unestablished, the collective evidence is compelling. This review explores unconventional perspectives and emerging paradigms regarding microbial involvement in AD pathogenesis, emphasizing the gut–brain axis, brain biofilms, the oral microbiome, and viral infections. Transgenic mouse models show that gut microbiota dysregulation precedes brain Aβ accumulation, emphasizing gut–brain signaling pathways. Viral infections like Herpes Simplex Virus Type 1 (HSV-1) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) may lead to AD by modulating host processes like the immune system. Aβ peptide’s antimicrobial function as a response to microbial infection might inadvertently promote AD. We discuss potential microbiome-based therapies as promising strategies for managing and potentially preventing AD progression. Fecal microbiota transplantation (FMT) restores gut microbial balance, reduces Aβ accumulation, and improves cognition in preclinical models. Probiotics and prebiotics reduce neuroinflammation and Aβ plaques, while antiviral therapies targeting HSV-1 and vaccines like the shingles vaccine show potential to mitigate AD pathology. Developing effective treatments requires standardized methods to identify and measure microbial infections in AD patients, enabling personalized therapies that address individual microbial contributions to AD pathogenesis. Further research is needed to clarify the interactions between microbes and Aβ, explore bacterial and viral interplay, and understand their broader effects on host processes to translate these insights into clinical interventions. Full article
(This article belongs to the Special Issue Latest Review Papers in Medical Microbiology 2024)
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19 pages, 1010 KB  
Review
Exploring microRNA-Mediated Immune Responses to Soil-Transmitted Helminth and Herpes Simplex Virus Type 2 Co-Infections
by Roxanne Pillay, Pragalathan Naidoo and Zilungile L. Mkhize-Kwitshana
Diseases 2025, 13(1), 6; https://doi.org/10.3390/diseases13010006 - 1 Jan 2025
Viewed by 2124
Abstract
Over the last two decades, the field of microRNA (miRNA) research has grown significantly. MiRNAs are a class of short, single-stranded, non-coding RNAs that regulate gene expression post-transcriptionally. Thereby, miRNAs regulate various essential biological processes including immunity. Dysregulated miRNAs are associated with various [...] Read more.
Over the last two decades, the field of microRNA (miRNA) research has grown significantly. MiRNAs are a class of short, single-stranded, non-coding RNAs that regulate gene expression post-transcriptionally. Thereby, miRNAs regulate various essential biological processes including immunity. Dysregulated miRNAs are associated with various infectious and non-infectious diseases. Recently co-infection with soil-transmitted helminths (STHs) and herpes simplex virus type 2 (HSV-2) has become a focus of study. Both pathogens can profoundly influence host immunity, particularly in under-resourced and co-endemic regions. It is well known that STHs induce immunomodulatory responses that have bystander effects on unrelated conditions. Typically, STHs induce T-helper 2 (Th2) and immunomodulatory responses, which may dampen the proinflammatory T-helper 1 (Th1) immune responses triggered by HSV-2. However, the extent to which STH co-infection influences the host immune response to HSV-2 is not well understood. Moreover, little is known about how miRNAs shape the immune response to STH/HSV-2 co-infection. In this article, we explore the potential influence that STH co-infection may have on host immunity to HSV-2. Because STH and HSV-2 infections are widespread and disproportionately affect vulnerable and impoverished countries, it is important to consider how STHs may impact HSV-2 immunity. Specifically, we explore how miRNAs contribute to both helminth and HSV-2 infections and discuss how miRNAs may mediate STH/HSV-2 co-infections. Insight into miRNA-mediated immune responses may further improve our understanding of the potential impact of STH/HSV-2 co-infections. Full article
(This article belongs to the Topic miRNAs in Pathophysiology of Disease)
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