-
Human Vaccines & Immunotherapeutics Dec 2023The growing burden of herpes zoster (HZ) in Hong Kong, due to an aging population with increasing life expectancy, may be reduced by vaccination. This study aimed to...
The growing burden of herpes zoster (HZ) in Hong Kong, due to an aging population with increasing life expectancy, may be reduced by vaccination. This study aimed to estimate public health impact of HZ vaccination in Hong Kong. The ZOster ecoNomic Analysis (ZONA) model was adapted with Hong Kong-specific key model inputs/assumptions, where available. Base case analysis involved adults ≥50 years of age (YOA), exploring three vaccination strategies (no vaccination/recombinant zoster vaccine [RZV]/zoster vaccine live [ZVL]) under private market (5% coverage) and mass vaccination (40% coverage) settings. Scenario and sensitivity analyses were performed. In the base case population (3.13 million), without vaccination, 891,024 HZ (28.4%), 156,097 post-herpetic neuralgia (PHN) (5.0%), and 38,755 (1.2%) HZ ophthalmicus (HZO) were projected over their remaining lifetime. Mass RZV vaccination reduced HZ, PHN, and HZO cases by 204,875 (-23.0%), 31,949 (-20.5%), and 8,471 (-21.9%), respectively, which was 4-5 times that reduced with ZVL. RZV was more efficient than ZVL, with lower number needed to vaccinate to prevent one HZ/PHN/HZO case (RZV: 7/40/148; ZVL: 27/163/709). Among all age cohorts, the greatest reduction in cases was projected for RZV (versus no vaccination/ZVL) in the youngest cohort, 50-59 YOA. Results were robust under scenario and sensitivity analyses. HZ burden in Hong Kong is substantial. Mass RZV vaccination is expected to considerably reduce public health burden of HZ among individuals ≥50 YOA, compared with no vaccination/ZVL. Results may support value assessment and decision-making regarding vaccination strategies for HZ prevention in Hong Kong.
Topics: Humans; Aged; Herpes Zoster Vaccine; Public Health; Hong Kong; Cost-Benefit Analysis; Herpes Zoster; Neuralgia, Postherpetic; Vaccination; Herpesvirus 3, Human; Vaccines, Synthetic
PubMed: 36854447
DOI: 10.1080/21645515.2023.2176065 -
PLoS Pathogens Sep 2023Previously we reported that the HSV-1 latency associated transcript (LAT) specifically upregulates the cellular herpesvirus entry mediator (HVEM) but no other known...
Previously we reported that the HSV-1 latency associated transcript (LAT) specifically upregulates the cellular herpesvirus entry mediator (HVEM) but no other known HSV-1 receptors. HSV-1 glycoprotein D (gD) binds to HVEM but the effect of this interaction on latency-reactivation is not known. We found that the levels of latent viral genomes were not affected by the absence of gD binding to HVEM. However, reactivation of latent virus in trigeminal ganglia explant cultures was blocked in the absence of gD binding to HVEM. Neither differential HSV-1 replication and spread in the eye nor levels of latency influenced reactivation. Despite similar levels of latency, reactivation in the absence of gD binding to HVEM correlated with reduced T cell exhaustion. Our results indicate that HVEM-gD signaling plays a significant role in HSV-1 reactivation but not in ocular virus replication or levels of latency. The results presented here identify gD binding to HVEM as an important target that influences reactivation and survival of ganglion resident T cells but not levels of latency. This concept may also apply to other herpesviruses that engages HVEM.
Topics: Herpesvirus 1, Human; Receptors, Tumor Necrosis Factor, Member 14; Eye; Virus Replication; Virus Latency
PubMed: 37738264
DOI: 10.1371/journal.ppat.1011693 -
European Journal of Medical Research Oct 2023Infection rate of varicella zoster virus (VZV) is 95% in humans, and VZV infection is strongly associated with ischemic stroke (IS). However, the underlying molecular...
BACKGROUND
Infection rate of varicella zoster virus (VZV) is 95% in humans, and VZV infection is strongly associated with ischemic stroke (IS). However, the underlying molecular mechanisms of VZV-induced IS are still unclear, and there are no effective agents to treat and prevent VZV-induced IS.
OBJECTIVE
By integrating bioinformatics, this study explored the interactions between VZV and IS and potential medication to treat and prevent VZV-induced IS.
METHODS
In this study, the VZV and IS datasets from the GEO database were used to specify the common genes. Then, bioinformatics analysis including Gene Ontology, Kyoto Encyclopedia Genes Genomes and Protein-Protein Interaction network analysis was performed. Further, the hub genes, transcription factor (TF) gene interactions, TF-miRNA co-regulatory network and potential drug were obtained. Finally, validation was performed using molecular docking and molecular dynamics simulations.
RESULTS
The potential molecular mechanisms of VZV-induced IS were studied using multiple bioinformatics tools. Ten hub genes were COL1A2, DCN, PDGFRB, ACTA2, etc. TF genes and miRNAs included JUN, FOS, CREB, BRCA1, PPARG, STAT3, miR-29, etc. A series of mechanism may be involved, such as inflammation, oxidative stress, blood-brain barrier disruption, foam cell generation and among others. Finally, we proposed resveratrol as a potential therapeutic medicine for the prevention and treatment of VZV-induced IS. Molecular docking and molecular dynamics results showed that resveratrol and hub genes exhibited strong binding score.
CONCLUSIONS
Resveratrol could be an alternative for the prevention and treatment of VZV-IS. More in vivo and in vitro studies are needed in the future to fully explore the molecular mechanisms between VZV and IS and for medication development.
Topics: Humans; Herpesvirus 3, Human; Herpes Zoster; Resveratrol; Ischemic Stroke; Molecular Docking Simulation; MicroRNAs
PubMed: 37794518
DOI: 10.1186/s40001-023-01291-4 -
Journal of Virology Oct 2023Herpes simplex virus 1 is an important human pathogen that has been intensively studied for many decades. Nevertheless, the molecular mechanisms regulating its...
Herpes simplex virus 1 is an important human pathogen that has been intensively studied for many decades. Nevertheless, the molecular mechanisms regulating its establishment, maintenance, and reactivation from latency are poorly understood. Here, we show that HSV-1-encoded miR-H2 is post-transcriptionally edited in latently infected human tissues. Hyperediting of viral miRNAs increases the targeting potential of these miRNAs and may play an important role in regulating latency. We show that the edited miR-H2 can target ICP4, an essential viral protein. Interestingly, we found no evidence of hyperediting of its homolog, miR-H2, which is expressed by the closely related virus HSV-2. The discovery of post-translational modifications of viral miRNA in the latency phase suggests that these processes may also be important for other non-coding viral RNA in the latency phase, including the intron LAT, which in turn may be crucial for understanding the biology of this virus.
Topics: Humans; MicroRNAs; Herpesvirus 1, Human; Virus Latency; Viral Proteins; Ganglia; Trigeminal Ganglion; Herpes Simplex; Virus Activation
PubMed: 37712701
DOI: 10.1128/jvi.00730-23 -
Cleveland Clinic Journal of Medicine Oct 2023
Topics: Humans; Chickenpox; Herpesvirus 3, Human; Herpes Zoster; Vaccines
PubMed: 37783498
DOI: 10.3949/ccjm.90a.23008 -
Skin manifestations after immunisation with an adjuvanted recombinant zoster vaccine, Germany, 2020.Euro Surveillance : Bulletin Europeen... Dec 2023BackgroundShortly after the launch of a novel adjuvanted recombinant zoster vaccine (RZV), Shingrix, cases of suspected herpes zoster (HZ) or zoster-like skin reactions...
BackgroundShortly after the launch of a novel adjuvanted recombinant zoster vaccine (RZV), Shingrix, cases of suspected herpes zoster (HZ) or zoster-like skin reactions following immunisation were reported.AimWe aimed to investigate if these skin manifestations after administration of RZV could be HZ.MethodsBetween April and October 2020, general practitioners (GP) reporting a suspected case of HZ or zoster-like skin manifestation after RZV vaccination to the Paul-Ehrlich-Institut, the German national competent authority, were invited to participate in the study. The GP took a sample of the skin manifestation, photographed it and collected patient information on RZV vaccination and the suspected adverse event. We analysed all samples by PCR for varicella-zoster virus (VZV) and herpes-simplex virus (HSV) and genotyped VZV-positive samples. In addition, cases were independently assessed by two dermatologists.ResultsEighty eligible cases were enrolled and 72 could be included in the analysis. Of the 72 cases, 45 were female, 33 were 60-69 years old, 32 had skin symptoms in the thoracic and 27 in the cervical dermatomes. Twenty-seven samples tested PCR positive for VZV (all genotyped as wild-type, WT), three for HSV-1 and five for HSV-2.ConclusionIt may be difficult to distinguish HZ, without a PCR result, from other zoster-like manifestations. In this study, VZV-PCR positive dermatomal eruptions occurring in the first weeks after immunisation with RZV were due to WT VZV, which is not unexpected as HZ is a common disease against which the vaccine is unlikely to provide full protection at this time.
Topics: Female; Humans; Middle Aged; Aged; Male; Herpes Zoster Vaccine; Herpes Zoster; Herpesvirus 3, Human; Vaccination; Vaccines, Synthetic; Germany
PubMed: 38099347
DOI: 10.2807/1560-7917.ES.2023.28.50.2300261 -
Journal of Virology Jul 2023Pseudorabies virus (PRV), the causative pathogen of Aujeszky's disease, is one of the most important pathogens threatening the global pig industry. Although vaccination...
Pseudorabies virus (PRV), the causative pathogen of Aujeszky's disease, is one of the most important pathogens threatening the global pig industry. Although vaccination has been used to prevent PRV infection, the virus cannot be eliminated in pigs. Thus, novel antiviral agents as complementary to vaccination are urgently needed. Cathelicidins (CATHs) are host defense peptides that play an important role in the host immune response against microbial infections. In the study, we found that the chemical synthesized chicken cathelicidin B1 (CATH-B1) could inhibit PRV regardless of whether CATH-B1 was added pre-, co-, or post-PRV infection and . Furthermore, coincubation of CATH-B1 with PRV directly inactivated virus infection by disrupting the virion structure of PRV and mainly inhibited virus binding and entry. Importantly, pretreatment of CATH-B1 markedly strengthened the host antiviral immunity, as indicated by the increased expression of basal interferon-β (IFN-β) and several IFN-stimulated genes (ISGs). Subsequently, we investigated the signaling pathway responsible for CATH-B1-induced IFN-β production. Our results showed that CATH-B1 induced phosphorylation of interferon regulatory transcription factor 3 (IRF3) and further led to production of IFN-β and reduction of PRV infection. Mechanistic studies revealed that the activation of Toll-like receptor 4 (TLR4), endosome acidification, and the following c-Jun N-terminal kinase (JNK) was responsible for CATH-B1-induced IRF3/IFN-β pathway activation. Collectively, CATH-B1 could markedly inhibit PRV infection via inhibiting virus binding and entry, direct inactivation, and regulating host antiviral response, which provided an important theoretical basis for the development of antimicrobial peptide drugs against PRV infection. Although the antiviral activity of cathelicidins could be explained by direct interfering with the viral infection and regulating host antiviral response, the specific mechanism of cathelicidins regulating host antiviral response and interfering with pseudorabies virus (PRV) infection remains elusive. In this study, we investigated the multiple roles of cathelicidin CATH-B1 against PRV infection. Our study showed that CATH-B1 could suppress the binding and entry stages of PRV infection and direct disrupt PRV virions. Remarkably, CATH-B1 significantly increased basal interferon-β (IFN-β) and IFN-stimulated gene (ISG) expression levels. Furthermore, TLR4/c-Jun N-terminal kinase (JNK) signaling was activated and involved in IRF3/IFN-β activation in response to CATH-B1. In conclusion, we elucidate the mechanisms by which the cathelicidin peptide direct inactivates PRV infection and regulates host antiviral IFN-β signaling.
Topics: Swine; Animals; Herpesvirus 1, Suid; Cathelicidins; Toll-Like Receptor 4; Interferon-beta; Antiviral Agents; Pseudorabies
PubMed: 37314341
DOI: 10.1128/jvi.00706-23 -
Human Vaccines & Immunotherapeutics Dec 2023The currently used Japanese Oka and Korean MAV/06-attenuated varicella vaccine strains belong to clade 2 genotype varicella-zoster viruses (VZV). More than seven clades...
The currently used Japanese Oka and Korean MAV/06-attenuated varicella vaccine strains belong to clade 2 genotype varicella-zoster viruses (VZV). More than seven clades of VZV exist worldwide. In this study, we investigated the cross-reactivity of antibodies induced by clade 2 genotype vaccines against VZV strains belonging to clades 1, 2, 3, and 5 using a fluorescent antibody to membrane antigen (FAMA) test. Among 59 donors, 29 were vaccinated with the MAV/06 strain MG1111 (GC Biopharma, South Korea) and the other 30 were vaccinated with the Oka strain VARIVAX (Merck, USA). The sera were titrated using FAMA tests prepared with six different VZV strains (two vaccine strains, one wild-type clade 2 strain, and one each of clade 1, 3, and 5 strains). The ranges of geometric mean titers (GMTs) of FAMA against six different strains were 158.7-206.5 and 157.6-238.9 in MG1111 and VARIVAX groups, respectively. GMTs of the MG1111 group against all six strains were similar; however, GMTs of the VARIVAX group showed differences of approximately 1.5-fold depending on the strains. Nevertheless, the GMTs of the two vaccinated groups for the same strain were not significantly different. These results suggest that both MG1111 and VARIVAX vaccinations induce cross-reactive humoral immunity against other clades of VZV.
Topics: Humans; Herpesvirus 3, Human; Chickenpox Vaccine; Chickenpox; Immunity, Humoral; Viral Vaccines; Vaccines, Attenuated; Antigens, Viral
PubMed: 37218543
DOI: 10.1080/21645515.2023.2210961 -
Reducing lipid peroxidation attenuates stress-induced susceptibility to herpes simplex virus type 1.Acta Pharmacologica Sinica Sep 2023Psychological stress increases the susceptibility to herpes simplex virus type 1 (HSV-1) infection. There is no effective intervention due to the unknown pathogenesis...
Psychological stress increases the susceptibility to herpes simplex virus type 1 (HSV-1) infection. There is no effective intervention due to the unknown pathogenesis mechanisms. In this study we explored the molecular mechanisms underlying stress-induced HSV-1 susceptibility and the antiviral effect of a natural compound rosmarinic acid (RA) in vivo and in vitro. Mice were administered RA (11.7, 23.4 mg·kg·d, i.g.) or acyclovir (ACV, 206 mg·kg·d, i.g.) for 23 days. The mice were subjected to restraint stress for 7 days followed by intranasal infection with HSV-1 on D7. At the end of RA or ACV treatment, mouse plasma samples and brain tissues were collected for analysis. We showed that both RA and ACV treatment significantly decreased stress-augmented mortality and alleviated eye swelling and neurological symptoms in HSV-1-infected mice. In SH-SY5Y cells and PC12 cells exposed to the stress hormone corticosterone (CORT) plus HSV-1, RA (100 μM) significantly increased the cell viability, and inhibited CORT-induced elevation in the expression of viral proteins and genes. We demonstrated that CORT (50 μM) triggered lipoxygenase 15 (ALOX15)-mediated redox imbalance in the neuronal cells, increasing the level of 4-HNE-conjugated STING, which impaired STING translocation from the endoplasmic reticulum to Golgi; the abnormality of STING-mediated innate immunity led to HSV-1 susceptibility. We revealed that RA was an inhibitor of lipid peroxidation by directly targeting ALOX15, thus RA could rescue stress-weakened neuronal innate immune response, thereby reducing HSV-1 susceptibility in vivo and in vitro. This study illustrates the critical role of lipid peroxidation in stress-induced HSV-1 susceptibility and reveals the potential for developing RA as an effective intervention in anti-HSV-1 therapy.
Topics: Humans; Animals; Mice; Herpesvirus 1, Human; Lipid Peroxidation; Neuroblastoma; Acyclovir; Herpes Simplex
PubMed: 37193755
DOI: 10.1038/s41401-023-01095-6 -
Viruses May 2024Marek's disease (MD), caused by (GaAHV2) or Marek's disease herpesvirus (MDV), is a devastating disease in chickens characterized by the development of lymphomas...
Marek's disease (MD), caused by (GaAHV2) or Marek's disease herpesvirus (MDV), is a devastating disease in chickens characterized by the development of lymphomas throughout the body. Vaccine strains used against MD include 3 (GaAHV3), a non-oncogenic chicken alphaherpesvirus homologous to MDV, and homologous meleagrid alphaherpesvirus 1 (MeAHV1) or turkey herpesvirus (HVT). Previous work has shown most of the MDV gC produced during in vitro passage is secreted into the media of infected cells although the predicted protein contains a transmembrane domain. We formerly identified two alternatively spliced gC mRNAs that are secreted during MDV replication in vitro, termed gC104 and gC145 based on the size of the intron removed for each (gC) transcript. Since gC is conserved within the subfamily, we hypothesized GaAHV3 (strain 301B/1) and HVT also secrete gC due to mRNA splicing. To address this, we collected media from 301B/1- and HVT-infected cell cultures and used Western blot analyses and determined that both 301B/1 and HVT produced secreted gC. Next, we extracted RNAs from 301B/1- and HVT-infected cell cultures and chicken feather follicle epithelial (FFE) skin cells. RT-PCR analyses confirmed one splicing variant for 301B/1 gC (gC104) and two variants for HVT gC (gC104 and gC145). Interestingly, the splicing between all three viruses was remarkably conserved. Further analysis of predicted and validated mRNA splicing donor, branch point (BP), and acceptor sites suggested single nucleotide polymorphisms (SNPs) within the 301B/1 transcript sequence resulted in no gC145 being produced. However, modification of the 301B/1 gC145 donor, BP, and acceptor sites to the MDV sequences did not result in gC145 mRNA splice variant, suggesting mRNA splicing is more complex than originally hypothesized. In all, our results show that mRNA splicing of avian herpesviruses is conserved and this information may be important in developing the next generation of MD vaccines or therapies to block transmission.
Topics: Animals; Chickens; RNA Splicing; Viral Envelope Proteins; RNA, Messenger; Marek Disease; Mardivirus; Viral Proteins; Herpesvirus 2, Gallid; Alternative Splicing; Antigens, Viral
PubMed: 38793663
DOI: 10.3390/v16050782