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18 pages, 25244 KiB  
Article
The Procaine-Based ProcCluster® Impedes the Second Envelopment Process of Herpes Simplex Virus Type 1
by Johannes Jungwirth, Lisa Siegert, Lena Gauthier, Andreas Henke, Oliver H. Krämer, Beatrice Engert and Christina Ehrhardt
Int. J. Mol. Sci. 2025, 26(15), 7185; https://doi.org/10.3390/ijms26157185 - 25 Jul 2025
Viewed by 209
Abstract
Herpes simplex virus type 1 (HSV-1) has a global prevalence of 64%. Established antiviral drugs, such as acyclovir (ACV), have been successfully used over the past decades. However, due to growing viral resistance against approved antivirals and the lack of effective vaccines, new [...] Read more.
Herpes simplex virus type 1 (HSV-1) has a global prevalence of 64%. Established antiviral drugs, such as acyclovir (ACV), have been successfully used over the past decades. However, due to growing viral resistance against approved antivirals and the lack of effective vaccines, new concepts are essential to target HSV-1 infections. Here, we present data on the inhibitory effect of the procaine-based substance ProcCluster® (PC) in reducing HSV-1 replication in vitro. Non-toxic PC concentrations significantly decreased HSV-1 replication in infected cells. Immunofluorescence microscopy revealed an accumulation of viral proteins in early and recycling endosomes, resulting in reduced viral release. The combination of PC with ACV resulted in an enhanced antiviral effect. Based on these results, PC alone, as well as in combination with ACV, appears to be a promising substance with antiviral potential against HSV-1 infections. Full article
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27 pages, 1879 KiB  
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
Viewed by 1480
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 KiB  
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 865
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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15 pages, 1789 KiB  
Article
Seroconversion Is Misleading as a Test for HSV-2 Infection in Prophylactic Genital Herpes Vaccine Trials: Results of Vaccine Studies in Guinea Pigs
by Valerie Bromberg, Lauren M. Hook, John M. Lubinski, Zauraiz Syeda, Kevin P. Egan, Gary H. Cohen, Sita Awasthi and Harvey M. Friedman
Viruses 2025, 17(6), 773; https://doi.org/10.3390/v17060773 - 29 May 2025
Viewed by 966
Abstract
Seroconversion is defined as a four-fold or greater rise in antibody titers. This assay is used in human prophylactic vaccine trials to confirm HSV as the cause of genital lesions and detect subclinical latent infection. We evaluated the accuracy of seroconversion in detecting [...] Read more.
Seroconversion is defined as a four-fold or greater rise in antibody titers. This assay is used in human prophylactic vaccine trials to confirm HSV as the cause of genital lesions and detect subclinical latent infection. We evaluated the accuracy of seroconversion in detecting infection using a guinea pig model of genital infection. Not all animals intravaginally inoculated with HSV-2 become infected, particularly if vaccinated; therefore, we need to establish criteria to determine whether an animal is infected. Our primary analysis involved considering animals to be infected if they had any of the following: (a) genital lesions; (b) HSV-2 DNA in vaginal secretions four or more weeks after HSV-2 inoculation as a marker of reactivation from latency; or (c) HSV-2 DNA in dorsal root ganglia, the site of latency. In the second analysis, we considered animals to be infected if they had positive virus cultures from vaginal swabs obtained on day two or four post HSV-2 inoculation. In the third analysis, we considered animals to be infected if they had any condition included in the first two analyses. We collected sera prior to HSV-2 inoculation and two months later and tested the first 57 animals for seroconversion using Western blotting and gG2 IgG ELISA. The results were concordant in 54 of 57 animals (95%), and when discordant, the gG2 ELISA matched infection results as defined by the primary analysis. The remaining animals were evaluated by gG2 IgG ELISA only. A total of 43 animals were inoculated with HSV-2 but not vaccinated (No vaccine group), and 224 were vaccinated with glycoprotein or mRNA vaccines prior to HSV-2 inoculation (Vaccine group). In the No vaccine group, we detected no false positives (seroconversion without infection) but 24% to 29% false negatives (no seroconversion despite infection) depending on the criteria used to define infection. In the Vaccine group, we detected 8% to 22% false positives and 31% to 37% false negatives. The accuracy of seroconversion was 74% to 79% in the No vaccine group and 71% to 76% in the Vaccine group. These results raise concerns about using seroconversion as a diagnostic test in human vaccine trials. Alternate approaches, such as subject home swabbing for HSV DNA, should be considered as a possible replacement. Full article
(This article belongs to the Special Issue Herpesviruses and Associated Diseases)
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17 pages, 312 KiB  
Review
Human Alpha Herpesviruses Infections (HSV1, HSV2, and VZV), Alzheimer’s Disease, and the Potential Benefits of Targeted Treatment or Vaccination—A Virological Perspective
by Peter A. C. Maple and Akram A. Hosseini
Vaccines 2025, 13(6), 572; https://doi.org/10.3390/vaccines13060572 - 27 May 2025
Viewed by 2121
Abstract
Understanding the contribution of human herpesviruses to the aetiology of neurodegenerative diseases is an emerging field of interest. The association of Epstein–Barr virus with multiple sclerosis is the most researched example; however, the definitive proof of causation is still lacking. Alzheimer’s disease (AD) [...] Read more.
Understanding the contribution of human herpesviruses to the aetiology of neurodegenerative diseases is an emerging field of interest. The association of Epstein–Barr virus with multiple sclerosis is the most researched example; however, the definitive proof of causation is still lacking. Alzheimer’s disease (AD) is the most common form of dementia and typically manifests in individuals aged over 65 years; however, it also occurs in a small number of individuals aged less than 65 years. A combination of environmental, genetic, and lifestyle factors is believed to contribute to the development of AD. There have been several reports describing potential associations of infections or reactivations of human alphaherpesviruses with AD. A particular characteristic of human alphaherpesviruses (herpes simplex viruses 1 and 2, varicella zoster virus) is that they are neurotropic and that lifelong infection (latency) is established mainly in the dorsal root and trigeminal ganglia. There have also been reports that suppression of alphaherpesvirus infections through either vaccination or the application of antiviral treatments may be protective against the development of AD. Zoster vaccines and acyclovir may prove to be effective interventions for preventing or limiting the progression of AD. This is particularly relevant as there are currently no available cheap and effective treatments for AD. In this review, the basic virology of human alphaherpesviruses is described followed by their epidemiology and associations with AD. Finally, the prevention and treatment of human alphaherpesviruses are considered in the context of potential applications for the prevention of AD. Full article
(This article belongs to the Special Issue Varicella and Zoster Vaccination)
18 pages, 3875 KiB  
Article
A QS21 + CpG-Adjuvanted Trivalent HSV-2 Vaccine and Trivalent HSV-2 mRNA Vaccine Induce a Strong Immune Response, Protect Against HSV-2 Infection, and Cross-Protect Against HSV-1 Infection in Mice
by Han Cao, Xiaolong Zhang, Jishuai Cheng, Yang Li, Ning Luan, Jingping Hu, Bingyan Liang, Haihao Zhang, Dandan Gao, Zhentao Lei, Yufeng Yao and Cunbao Liu
Vaccines 2025, 13(5), 497; https://doi.org/10.3390/vaccines13050497 - 6 May 2025
Cited by 1 | Viewed by 1236
Abstract
Background: HSV-2 infection continues to be a significant global health concern, as there are no approved vaccines despite numerous attempts at development. Methods: This study explored the immunogenicity and protective efficacy of aluminum- or QS21 + CpG-adjuvanted trivalent HSV-2 vaccines and a trivalent [...] Read more.
Background: HSV-2 infection continues to be a significant global health concern, as there are no approved vaccines despite numerous attempts at development. Methods: This study explored the immunogenicity and protective efficacy of aluminum- or QS21 + CpG-adjuvanted trivalent HSV-2 vaccines and a trivalent HSV-2 mRNA vaccine incorporating the gC2, gD2, and gE2 antigens. Results: Our results demonstrated that the QS21 + CpG-adjuvanted subunit vaccine and mRNA vaccines successfully induced robust antigen-specific humoral and cellular immune responses and provided significant protection against both HSV-2 and HSV-1 infection. These vaccines showed remarkable efficiency in reducing the viral load and preventing clinical symptoms in mice, highlighting their potential for clinical application. Conversely, the aluminum-adjuvanted vaccine exhibited limited effectiveness, emphasizing the superiority of the QS21 + CpG-adjuvanted and mRNA vaccines. Conclusions: These findings provide valuable insights for the continued development of effective HSV vaccines and suggest promising strategies for preventing both HSV-2 and HSV-1 infection. Full article
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33 pages, 1847 KiB  
Review
Immunological Control of Herpes Simplex Virus Type 1 Infection: A Non-Thermal Plasma-Based Approach
by Julia Sutter, Jennifer L. Hope, Brian Wigdahl, Vandana Miller and Fred C. Krebs
Viruses 2025, 17(5), 600; https://doi.org/10.3390/v17050600 - 23 Apr 2025
Viewed by 1420
Abstract
Herpes simplex virus type 1 (HSV-1) causes a lifelong infection due to latency established in the trigeminal ganglia, which is the source of recurrent outbreaks of cold sores. The lifelong persistence of HSV-1 is further facilitated by the lack of cure strategies, unsuccessful [...] Read more.
Herpes simplex virus type 1 (HSV-1) causes a lifelong infection due to latency established in the trigeminal ganglia, which is the source of recurrent outbreaks of cold sores. The lifelong persistence of HSV-1 is further facilitated by the lack of cure strategies, unsuccessful vaccine development, and the inability of the host immune system to clear HSV-1. Despite the inefficiencies of the immune system, the course of HSV-1 infection remains under strict immunological control. Specifically, HSV-1 is controlled by a CD8+ T cell response that is cytotoxic to HSV-1-infected cells, restricts acute infection, and uses noncytolytic mechanisms to suppress reactivation in the TG. When this CD8+ T cell response is disrupted, reactivation of latent HSV-1 occurs. With antiviral therapies unable to cure HSV-1 and prophylactic vaccine strategies failing to stimulate a protective response, we propose non-thermal plasma (NTP) as a potential therapy effective against recurrent HSV-1 infection. We have demonstrated that NTP, when applied directly to HSV-1-infected cells, has antiviral effects and stimulates cellular stress and immunomodulatory responses. We further propose that the direct effects of NTP will lead to long-lasting indirect effects such as reduced viral seeding into the TG and enhanced HSV-1-specific CD8+ T cell responses that exert greater immune control over HSV-1 infection. Full article
(This article belongs to the Special Issue Herpesviruses and Associated Diseases)
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13 pages, 2156 KiB  
Article
Analysis of the Interaction Between the Attenuated HSV-1 Strain M6 and Macrophages Indicates Its Potential as an Effective Vaccine Immunogen
by Zhenxiao Zhang, Xiaohong Ren, Ying Zhang, Jingjing Zhang, Xinghang Li, Fengyuan Zeng, Rong Yue, Qi Li, Haobo Zhang, Danjing Ma, Yuansheng Liao, Yun Liao, Dandan Li, Li Yu, Guorun Jiang, Heng Zhao, Huiwen Zheng, Heng Li, Xin Zhao, Longding Liu and Qihan Liadd Show full author list remove Hide full author list
Viruses 2025, 17(3), 392; https://doi.org/10.3390/v17030392 - 10 Mar 2025
Viewed by 742
Abstract
Herpes simplex virus type 1 (HSV-1) is a very concerning pathogen due to its ability to persist in the host’s nervous system and continuously interfere with the immune system, which complicates treatment. Therefore, the development of an effective HSV-1 vaccine is crucial. In [...] Read more.
Herpes simplex virus type 1 (HSV-1) is a very concerning pathogen due to its ability to persist in the host’s nervous system and continuously interfere with the immune system, which complicates treatment. Therefore, the development of an effective HSV-1 vaccine is crucial. In this study, we focused on an HSV-1 mutant strain, M6, which includes several deleted genes associated with viral infection virulence and latent infection function, and explored its infection of macrophages and immunological characteristics. The study found that both the attenuated strain M6 and the wild-type strain infect macrophages through the binding of the gD protein to the HVEM receptor on the macrophage surface. Compared to the wild-type strain, the attenuated M6 strain induced a milder immune response, characterized by the lower expression of immune signaling molecules and inflammatory cytokine levels. Upon reintroducing macrophages infected with the two strains into mice, the M6 strain induced lower levels of inflammatory cytokines and higher levels of chemokines in spleen cells and also slightly lower humoral and cellular immune responses than the wild-type strain. Further histopathological analysis revealed that mice in the attenuated M6 group showed more stable body weight changes and milder pathological damage in immune organs such as the liver, spleen, and lymph nodes. In conclusion, the attenuated M6 strain exhibits good immunogenicity and mild pathological side effects, suggesting its potential as an effective immunogen. Full article
(This article belongs to the Special Issue Herpesviruses and Associated Diseases)
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18 pages, 4935 KiB  
Article
Immunogenicity and Protective Efficacy of an mRNA Vaccine Targeting HSV-2 UL41 in Mice
by Tangwei Mou, Yu Zhao, Jie Jia, Kai-Cheng Gao, Shao-You Li and Yi-Qun Kuang
Vaccines 2025, 13(3), 271; https://doi.org/10.3390/vaccines13030271 - 5 Mar 2025
Cited by 1 | Viewed by 1220
Abstract
Background: Herpes simplex virus 2 (HSV-2) is the primary cause of sexually transmitted genital ulcerative diseases, for which no effective prophylactic vaccine is currently available. However, the identification of appropriate targets for an HSV-2 mRNA vaccine remains an area requiring further investigation. Methods: [...] Read more.
Background: Herpes simplex virus 2 (HSV-2) is the primary cause of sexually transmitted genital ulcerative diseases, for which no effective prophylactic vaccine is currently available. However, the identification of appropriate targets for an HSV-2 mRNA vaccine remains an area requiring further investigation. Methods: The immunogenicity and protective effects of an HSV-2 UL41 mRNA vaccine were evaluated in a BALB/c mouse model. The mice were intramuscularly immunized twice, followed by HSV-2 infection at 28 days post boost. Clinical signs were monitored daily, and the viral load and tissue inflammation were assessed on days 1, 4, and 7 post infection. Dendritic cell (DC) activation in spleen tissue was analyzed via transcriptome sequencing. Results: A comparison of the clinical, immunological, and pathological characteristics of the groups that were immunized with the UL41 mRNA vaccine and then infected with HSV2, along with the control groups, revealed that the vaccine elicited both cellular and humoral immunity, inhibited viral replication, suppressed the inflammatory response, and provided protective effects against the virus in vivo. Furthermore, in vitro assays of DC expansion revealed that the vaccine immunization increased the induction of DCs from splenic cells. Transcriptomic analysis of these DCs revealed the activation of immune signaling pathways. Conclusions: Our study suggests that the UL41 mRNA vaccine may provide effective protection against HSV-2-related diseases and holds promise as a potential mRNA vaccine candidate. Full article
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25 pages, 1432 KiB  
Systematic Review
Seroprevalence of TORCH Viral Agents in Pregnant Women in Turkey: Systematic Review and Meta-Analysis
by Elmas Pinar Kahraman Kilbas, Ihsan Hakki Ciftci, Imdat Kilbas and Hande Toptan
Pathogens 2025, 14(1), 37; https://doi.org/10.3390/pathogens14010037 - 6 Jan 2025
Cited by 1 | Viewed by 2004
Abstract
Rubella Virus, Cytomegalovirus (CMV), Herpes Simplex Virus-2 (HSV-2), Hepatitis B (HBV) and Hepatitis C virus (HCV) can cause serious fetal disease. The seropositivity rates of these agents vary among countries and geographic regions. This study aimed to analyze the prevalence rates and diagnostic [...] Read more.
Rubella Virus, Cytomegalovirus (CMV), Herpes Simplex Virus-2 (HSV-2), Hepatitis B (HBV) and Hepatitis C virus (HCV) can cause serious fetal disease. The seropositivity rates of these agents vary among countries and geographic regions. This study aimed to analyze the prevalence rates and diagnostic methods used in studies investigating the seroprevalence of viral pathogens in the TORCH group among pregnant women in Turkey between 2005 and 2024. A systematic search was conducted using electronic databases between January 2005 and January 2024. A total of 60 studies meeting the inclusion criteria were included. Data quality control was assessed using the Joanna Briggs Institute guideline prevalence studies checklist. Heterogeneity was measured using the I-squared (I2) statistic in the Comprehensive Meta Analysis (CMA) program. The average seropositivity rates for Rubella, CMV, HSV-2, HBV and HCV in Turkey were determined as 91.18%, 94.81%, 35.52%, 1.66% and 0.25%, respectively. When the diagnostic methods were examined, it was determined that ELISA and ECLIA methods were used most frequently. The seropositivity of the agents did not show statistically significant differences according to the year periods, geographical regions and age of the patients (p > 0.05). The highest prevalence rates of Rubella and HSV-2 in pregnant women were reported in the Mediterranean region, the highest prevalence rates of CMV and HCV in the Southeastern Anatolia region and the highest seroprevalence of Anti HBs in the Marmara region. The results of this study support the necessity of increasing public awareness in the control of fetal infection caused by TORCH viral agents, prenatal screening, vaccination for Rubella and HBV and compliance with hygiene conditions for agents such as CMV, HSV-2 and HCV. The results of this study highlight the need to increase public awareness on prenatal screening for the control of fetal infection caused by all TORCH viral agents, vaccination for Rubella and HBV and compliance with hygiene conditions for agents such as CMV, HSV-2 and HCV. Full article
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32 pages, 1321 KiB  
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 6 | Viewed by 5130
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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16 pages, 3607 KiB  
Article
Antiviral Activity of the Marine Haptophyta Diacronema lutheri
by Eleonora Montuori, Annalisa Ambrosino, Gerardo Della Sala, Costanza Ragozzino, Gianluigi Franci, Carla Zannella, Anna De Filippis, Donatella de Pascale, Massimiliano Galdiero and Chiara Lauritano
Mar. Drugs 2025, 23(1), 12; https://doi.org/10.3390/md23010012 - 28 Dec 2024
Viewed by 1526
Abstract
There are still several viral infections affecting a considerable number of the world’s population, causing thousands of deaths each year. There are no drugs available for most viral infections and for many not even a vaccine. The marine kingdom is characterized by a [...] Read more.
There are still several viral infections affecting a considerable number of the world’s population, causing thousands of deaths each year. There are no drugs available for most viral infections and for many not even a vaccine. The marine kingdom is characterized by a huge chemical diversity; however, there is currently on the market only one drug derived from the sea with antiviral properties, called Ara-A. In the current study, we used a solid phase extraction method (SPE) to obtain pre-purified fractions from Diacronema lutheri raw extracts. We tested both raw extracts and fractions against enveloped and non-enveloped viruses. Results showed an antiviral activity of fraction C of D. lutheri against the herpes simplex virus type 1 (HSV-1 strain SC16). Liquid chromatography coupled with untargeted high-resolution tandem mass spectrometry (LC-HRMS2) were employed to chart the metabolite distribution in all SPE fractions and pinpoint molecular families unique (or almost unique) to the bioactive fraction. Sulfoquinovosyl di- and monoacylglycerols (SQDGs and SQMGs) and di- and monogalactosyl monoacylglycerols (DGMGs and MGMGs) represent the largest groups of compounds in fraction C and they are likely responsible for the antiviral properties of this fraction. Full article
(This article belongs to the Special Issue Chemical Defense in Marine Organisms, 3rd Edition)
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11 pages, 1067 KiB  
Article
Deletion of gE in Herpes Simplex Virus 1 Leads to Increased Extracellular Virus Production and Augmented Interferon Alpha Production by Peripheral Blood Mononuclear Cells
by Manon Claeys, Jonas Delva, Cedric Jacqmotte, Cliff Van Waesberghe and Herman W. Favoreel
Pathogens 2024, 13(12), 1138; https://doi.org/10.3390/pathogens13121138 - 23 Dec 2024
Viewed by 1086
Abstract
Herpes simplex virus (HSV) in humans and pseudorabies virus (PRV) in pigs are both alphaherpesviruses. Plasmacytoid dendritic cells (pDCs) make part of the peripheral blood mononuclear cells (PBMCs) and are specialized in producing large amounts of antiviral type I interferon (IFN-I). IFN-I production [...] Read more.
Herpes simplex virus (HSV) in humans and pseudorabies virus (PRV) in pigs are both alphaherpesviruses. Plasmacytoid dendritic cells (pDCs) make part of the peripheral blood mononuclear cells (PBMCs) and are specialized in producing large amounts of antiviral type I interferon (IFN-I). IFN-I production by PBMCs in response to both HSV-1 and PRV can be virtually exclusively attributed to pDCs. Recently, we discovered that cells infected with gEnull PRV trigger increased production of IFNalpha by porcine PBMCs/pDCs compared with cells infected with wild-type (WT) PRV. This increased IFNalpha response correlates with increased extracellular virus production triggered by gEnull PRV compared with WT PRV. The gE protein and some of its currently described functions are conserved in different alphaherpesviruses, including PRV and HSV-1. In the current study, we report that cells infected with gEnull HSV-1 trigger increased IFNalpha production by human PBMCs and increased extracellular virus production compared with WT HSV-1. Hence, these recently described functions of PRV gE are conserved in HSV-1 gE. Since the increased extracellular virus production and IFNalpha response have also been reported for successful (gEnull) PRV vaccines, the current findings may have important consequences for the rational design of HSV vaccines. Full article
(This article belongs to the Section Viral Pathogens)
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21 pages, 5998 KiB  
Article
Immune Response Elicited by Recombinant Adenovirus-Delivered Glycoprotein B and Nucleocapsid Protein UL18 and UL25 of HSV-1 in Mice
by Haobo Zhang, Qi Li, Yun Liao, Danjing Ma, Fengyuan Zeng, Zhenxiao Zhang, Li Yu, Rong Yue, Xinghang Li, Yuansheng Liao, Dandan Li, Guorun Jang, Heng Zhao, Xin Zhao, Huiwen Zheng, Heng Li, Longding Liu and Ying Zhang
Int. J. Mol. Sci. 2024, 25(24), 13486; https://doi.org/10.3390/ijms252413486 - 16 Dec 2024
Cited by 1 | Viewed by 1318
Abstract
Due to the complex pathogenic and immune escape mechanisms of herpes simplex virus type 1 (HSV-1), especially the failure of induced immune responses to block the initial cell-to-cell transmission of the virus from skin cells to neurons, the body struggles to establish effective [...] Read more.
Due to the complex pathogenic and immune escape mechanisms of herpes simplex virus type 1 (HSV-1), especially the failure of induced immune responses to block the initial cell-to-cell transmission of the virus from skin cells to neurons, the body struggles to establish effective prevention and control methods, resulting in the failure of currently developed vaccines. Previous studies have highlighted the crucial roles of surface glycoproteins and nucleocapsid proteins in activating the body’s immune defense system against HSV-1 infection. In this study, recombinant adenoviruses were used as vectors to generate adenoviruses carrying the nucleocapsid protein genes UL18 and UL25, as well as the surface glycoprotein gene gB. This approach aimed to mimic the protein expression process that occurs following viral infection of the host and to investigate the immune response characteristics induced by UL18, UL25, and gB proteins. The findings revealed that UL18, UL25, and gB proteins could all trigger the expression of genes associated with innate immune responses; however, the specific genes induced varied in type and level. Furthermore, all three proteins were capable of promoting the proliferation of CD8+ T cells in the lymph nodes. Notably, only UL18 and gB could elicit a Th1 cell immune response. Interestingly, among these proteins, only UL18 could also induce a relatively higher IL-4 level, indicating a Th2 cell immune response. In addition to cellular immunity, all three proteins stimulated the production of specific IgG antibodies. Notably, UL18 induced higher and more sustained levels of specific IgG antibodies in mice. By contrast, only glycoprotein gB induced lower levels of neutralizing antibodies in mice. Moreover, when these mice were challenged with HSV-1, the co-immunization with UL18 and gB provided better protection than gB alone. In conclusion, HSV-1 surface glycoproteins and nucleocapsid proteins exhibit differences in their ability to induce innate and adaptive immunity in the body, suggesting potential avenues for vaccine design by leveraging their complementary advantages. Full article
(This article belongs to the Special Issue Recent Advances in Herpesviruses)
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17 pages, 1871 KiB  
Review
Breaching the Barrier: Investigating Initial Herpes Simplex Viral Infection and Spread in Human Skin and Mucosa
by Hafsa Rana, Naomi R. Truong, Dona R. Sirimanne and Anthony L. Cunningham
Viruses 2024, 16(11), 1790; https://doi.org/10.3390/v16111790 - 18 Nov 2024
Cited by 3 | Viewed by 2603
Abstract
Herpes simplex virus (HSV) is sexually transmitted via the anogenital mucosa where it initially infects epidermal keratinocytes and mononuclear phagocytes (MNPs). It then spreads to the dorsal root ganglion via sensory nerve endings, to remain latent for life with periodic reactivation. Currently, there [...] Read more.
Herpes simplex virus (HSV) is sexually transmitted via the anogenital mucosa where it initially infects epidermal keratinocytes and mononuclear phagocytes (MNPs). It then spreads to the dorsal root ganglion via sensory nerve endings, to remain latent for life with periodic reactivation. Currently, there is no cure or vaccine. Initial or recurrent HSV infection can produce serious complications and mediate acquisition of HIV. This review outlines the initial events after the HSV infection of human anogenital mucosa to determine the optimal window to target the virus before it becomes latent. After infection, HSV spreads rapidly within the mid-layers of epidermal keratinocytes in the explanted human inner foreskin. Infected cells produce chemokines, which modulate nectin-1 distribution on the surface of adjacent keratinocytes, facilitating viral spread. Epidermal Langerhans cells and dendritic cells become infected with HSV followed by a “viral relay” to dermal MNPs, which then present viral antigen to T cells in the dermis or lymph nodes. These data indicate the need for interruption of spread within 24 h by diffusible vaccine-induced mediators such as antiviral cytokines from resident immune cells or antibodies. Intradermal/mucosal vaccines would need to target the relevant dermal MNPs to induce HSV-specific CD4+ and CD8+ T cells. Full article
(This article belongs to the Special Issue Innate and Adaptive Immunity to Cutaneous Virus Infection)
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