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Viruses May 2024This study aims to evaluate the safety and immunogenicity of the SKYVaricella vaccine in healthy Vietnamese children aged 12 months to 12 years.
OBJECTIVE
This study aims to evaluate the safety and immunogenicity of the SKYVaricella vaccine in healthy Vietnamese children aged 12 months to 12 years.
METHODS
This open-label, single-arm study involved 201 children divided into two groups: 60 children aged 12 months to 5 years and 141 children aged 6 to 12 years. Safety was assessed through immediate reactions, solicited adverse events within 7 days, and unsolicited events up to Day 42. Immunogenicity was evaluated by seroconversion rates (SCR) and geometric mean titer (GMT) increments using fluorescent antibody-to-membrane antigen (FAMA) on the day of vaccination (D0) and 42 days after vaccination (D42).
RESULTS
All participants completed the follow-up. Immediate adverse events included pain (8.0%), redness (8.0%), and swelling (20.9%) at the injection site. Within 7 days, pain (17.9%) and swelling (12.4%) were mild and self-resolving. Unsolicited adverse events were infrequent and mild. Both age groups achieved 100% SCR. GMT of varicella-zoster virus antibodies increased from 1.37 (SD 1.97) at D0 to 18.02 (SD 2.22) at D42, a 13.12-fold rise. No Grade 3 adverse events were observed.
CONCLUSION
The SKYVaricella vaccine shows a robust immunogenic response and favorable safety profile in Vietnamese children aged 12 months to 12 years. These findings endorse its potential inclusion in pediatric vaccination programs as a reliable preventive option against varicella.
Topics: Humans; Male; Female; Vietnam; Child; Chickenpox Vaccine; Antibodies, Viral; Infant; Vaccines, Attenuated; Child, Preschool; Vaccination; Chickenpox; Immunogenicity, Vaccine; Herpesvirus 3, Human; Southeast Asian People
PubMed: 38932134
DOI: 10.3390/v16060841 -
Biosensors Jun 2024Development and optimisation of bioelectronic monitoring techniques like microelectrode array-based field potential measurement and impedance spectroscopy for the...
Development and optimisation of bioelectronic monitoring techniques like microelectrode array-based field potential measurement and impedance spectroscopy for the functional, label-free and non-invasive monitoring of in vitro neuronal networks is widely investigated in the field of biosensors. Thus, these techniques were individually used to demonstrate the capabilities of, e.g., detecting compound-induced toxicity in neuronal culture models. In contrast, extended application for investigating the effects of central nervous system infecting viruses are rarely described. In this context, we wanted to analyse the effect of herpesviruses on functional neuronal networks. Therefore, we developed a unique hybrid bioelectronic monitoring platform that allows for performing field potential monitoring and impedance spectroscopy on the same microelectrode. In the first step, a neuronal culture model based on primary hippocampal cells from neonatal rats was established with reproducible and stable synchronised electrophysiological network activity after 21 days of cultivation on microelectrode arrays. For a proof of concept, the pseudorabies model virus PrV Kaplan-ΔgG-GFP was applied and the effect on the neuronal networks was monitored by impedance spectroscopy and field potential measurement for 72 h in a multiparametric mode. Analysis of several bioelectronic parameters revealed a virus concentration-dependent degeneration of the neuronal network within 24-48 h, with a significant early change in electrophysiological activity, subsequently leading to a loss of activity and network synchronicity. In conclusion, we successfully developed a microelectrode array-based hybrid bioelectronic measurement platform for quantitative monitoring of pathologic effects of a herpesvirus on electrophysiological active neuronal networks.
Topics: Animals; Rats; Biosensing Techniques; Neurons; Dielectric Spectroscopy; Nerve Net; Microelectrodes; Hippocampus; Herpesvirus 1, Suid; Cells, Cultured; Pseudorabies
PubMed: 38920600
DOI: 10.3390/bios14060295 -
BMC Veterinary Research Jun 2024Equid alphaherpesvirus 1 (EHV-1) is a ubiquitous and significant viral pathogen in horses worldwide, causing a range of conditions, including fever, respiratory disease,...
Equid alphaherpesvirus 1 (EHV-1) is a ubiquitous and significant viral pathogen in horses worldwide, causing a range of conditions, including fever, respiratory disease, abortion in pregnant mares and the severe neurological disease called equine herpes myeloencephalopathy (EHM). Despite that EHV-1 is a notifiable animal disease in Sweden, there is limited knowledge about the circulating strains. This study aimed to analyze the genetic diversity of EHV-1 strains in equine samples from different Swedish outbreaks by partial genome sequencing. Genotyping based on three selected open reading frames ORF11, ORF30, and ORF34 in the viral genome was conducted for 55 outbreaks of EHV-1 spanning from the years 2012 to 2021. The analysis revealed 14 different genovariants, with one prominent genovariant identified in 49% of the outbreaks. Additionally, the study identified seven mutations not previously described. Three new mutations were demonstrated in ORF11, all synonymous, and four new mutations in ORF34, two synonymous, and two non-synonymous. Notably, different EHV-1 genovariants were found in five out of six studied EHM outbreaks, but clonal spreading was shown within the outbreaks. Moreover, the study demonstrated that healthy (recovered) horses that returned from an EHM outbreak at an international meeting in Valencia, Spain (2021), were positive for the virus clone responsible for the severe disease outbreak despite several weeks of quarantine. These findings shed light on the genetic diversity and transmission dynamics of the virus and significantly contribute to better understanding of the epidemiology of EHV-1 in Sweden and globally.
Topics: Animals; Horses; Sweden; Herpesvirus 1, Equid; Horse Diseases; Disease Outbreaks; Herpesviridae Infections; Genetic Variation; Genome, Viral; Genotype; Open Reading Frames
PubMed: 38909196
DOI: 10.1186/s12917-024-04096-7 -
Nature Communications Jun 2024During primary varicella zoster virus (VZV) infection, infected lymphocytes drive primary viremia, causing systemic dissemination throughout the host, including the...
During primary varicella zoster virus (VZV) infection, infected lymphocytes drive primary viremia, causing systemic dissemination throughout the host, including the skin. This results in cytokine expression, including interferons (IFNs), which partly limit infection. VZV also spreads from skin keratinocytes to lymphocytes prior to secondary viremia. It is not clear how VZV achieves this while evading the cytokine response. Here, we show that VZV glycoprotein C (gC) binds IFN-γ and modifies its activity, increasing the expression of a subset of IFN-stimulated genes (ISGs), including intercellular adhesion molecule 1 (ICAM1), chemokines and immunomodulatory genes. The higher ICAM1 protein level at the plasma membrane of keratinocytes facilitates lymphocyte function-associated antigen 1-dependent T cell adhesion and expression of gC during infection increases VZV spread to peripheral blood mononuclear cells. This constitutes the discovery of a strategy to modulate IFN-γ activity, upregulating a subset of ISGs, promoting enhanced lymphocyte adhesion and virus spread.
Topics: Humans; Interferon-gamma; Cell Adhesion; T-Lymphocytes; Intercellular Adhesion Molecule-1; Keratinocytes; Herpesvirus 3, Human; Varicella Zoster Virus Infection; Leukocytes, Mononuclear; Viral Envelope Proteins; Lymphocyte Function-Associated Antigen-1
PubMed: 38909022
DOI: 10.1038/s41467-024-49657-4 -
Frontiers in Immunology 2024Varicella zoster virus (VZV) causes varicella and can reactivate as herpes zoster, and both diseases present a significant burden worldwide. However, the mechanisms by...
INTRODUCTION
Varicella zoster virus (VZV) causes varicella and can reactivate as herpes zoster, and both diseases present a significant burden worldwide. However, the mechanisms by which VZV establishes latency in the sensory ganglia and disseminates to these sites remain unclear.
METHODS
We combined a single-cell sequencing approach and a well-established rhesus macaque experimental model using Simian varicella virus (SVV), which recapitulates the VZV infection in humans, to define the acute immune response to SVV in the lung as well as compare the transcriptome of infected and bystander lung-resident T cells and macrophages.
RESULTS AND DISCUSSION
Our analysis showed a decrease in the frequency of alveolar macrophages concomitant with an increase in that of infiltrating macrophages expressing antiviral genes as well as proliferating T cells, effector CD8 T cells, and T cells expressing granzyme A (GZMA) shortly after infection. Moreover, infected T cells harbored higher numbers of viral transcripts compared to infected macrophages. Furthermore, genes associated with cellular metabolism (glycolysis and oxidative phosphorylation) showed differential expression in infected cells, suggesting adaptations to support viral replication. Overall, these data suggest that SVV infection remodels the transcriptome of bystander and infected lung-resident T cells and macrophages.
Topics: Animals; Macaca mulatta; Lung; Macrophages, Alveolar; Transcriptome; T-Lymphocytes; Varicellovirus; Macrophages; Herpesviridae Infections; Herpesvirus 3, Human; Disease Models, Animal; Single-Cell Analysis
PubMed: 38887303
DOI: 10.3389/fimmu.2024.1408212 -
Nature Communications Jun 2024This study investigates the role of circular RNAs (circRNAs) in the context of Varicella-Zoster Virus (VZV) lytic infection. We employ two sequencing technologies,...
This study investigates the role of circular RNAs (circRNAs) in the context of Varicella-Zoster Virus (VZV) lytic infection. We employ two sequencing technologies, short-read sequencing and long-read sequencing, following RNase R treatment on VZV-infected neuroblastoma cells to identify and characterize both cellular and viral circRNAs. Our large scanning analysis identifies and subsequent experiments confirm 200 VZV circRNAs. Moreover, we discover numerous VZV latency-associated transcripts (VLTs)-like circRNAs (circVLTs), which contain multiple exons and different isoforms within the same back-splicing breakpoint. To understand the functional significance of these circVLTs, we utilize the Bacteria Artificial Chromosome system to disrupt the expression of viral circRNAs in genomic DNA location. We reveal that the sequence flanking circVLTs' 5' splice donor plays a pivotal role as a cis-acting element in the formation of circVLTs. The circVLTs is dispensable for VZV replication, but the mutation downstream of circVLTs exon 5 leads to increased acyclovir sensitivity in VZV infection models. This suggests that circVLTs may have a role in modulating the sensitivity to antiviral treatment. The findings shed new insight into the regulation of cellular and viral transcription during VZV lytic infection, emphasizing the intricate interplay between circRNAs and viral processes.
Topics: RNA, Circular; Herpesvirus 3, Human; Humans; RNA, Viral; Virus Replication; Cell Line, Tumor; Virus Latency; Varicella Zoster Virus Infection; Acyclovir; Exons
PubMed: 38858365
DOI: 10.1038/s41467-024-49112-4 -
Veterinary Research May 2024Pseudorabies virus (PRV) is recognized as the aetiological agent responsible for Aujeszky's disease, or pseudorabies, in swine populations. Rab6, a member of the small...
Pseudorabies virus (PRV) is recognized as the aetiological agent responsible for Aujeszky's disease, or pseudorabies, in swine populations. Rab6, a member of the small GTPase family, is implicated in various membrane trafficking processes, particularly exocytosis regulation. Its involvement in PRV infection, however, has not been documented previously. In our study, we observed a significant increase in the Rab6 mRNA and protein levels in both PK-15 porcine kidney epithelial cells and porcine alveolar macrophages, as well as in the lungs and spleens of mice infected with PRV. The overexpression of wild-type Rab6 and its GTP-bound mutant facilitated PRV proliferation, whereas the GDP-bound mutant form of Rab6 had no effect on viral propagation. These findings indicated that the GTPase activity of Rab6 was crucial for the successful spread of PRV. Further investigations revealed that the reduction in Rab6 levels through knockdown significantly hampered PRV proliferation and disrupted virus assembly and egress. At the molecular level, Rab6 was found to interact with the PRV glycoproteins gB and gE, both of which are essential for viral assembly and egress. Our results collectively suggest that PRV exploits Rab6 to expedite its assembly and egress and identify Rab6 as a promising novel target for therapeutic treatment for PRV infection.
Topics: Animals; Herpesvirus 1, Suid; Swine; rab GTP-Binding Proteins; Mice; Pseudorabies; Virus Release; Virus Assembly; Swine Diseases; Cell Line
PubMed: 38807225
DOI: 10.1186/s13567-024-01328-4 -
Virology Journal May 2024Equine herpesvirus type 1 (EHV-1) is commonly associated with horse abortion. Currently, there are no reported cases of abortion resulting from EHV-1 infection in...
BACKGROUND
Equine herpesvirus type 1 (EHV-1) is commonly associated with horse abortion. Currently, there are no reported cases of abortion resulting from EHV-1 infection in donkeys.
RESULTS
This was the first survey-based study of Chinese donkeys. The presence of EHV-1 was identified by PCR. This survey was conducted in Chabuchar County, North Xinjiang, China, in 2020. A donkey EHV-1 strain (Chabuchar/2020) was successfully isolated in MDBK cells. Seventy-two of 100 donkey sera were able to neutralize the isolated EHV-1. Moreover, the ORF33 sequence of the donkey-origin EHV-1 Chabuchar/2020 strain showed high levels of similarity in both its nucleotide (99.7‒100%) and amino acid (99.5‒100%) sequences, with those of horse EHV-1 strains. EHV-1 Chabuchar/2020 showed significant consistency and was classified within cluster 1 of horse EHV-1 strains. Further, analysis of the expected ORF30 nucleotide sequence revealed that donkey EHV-1 strains contained guanine at position 2254, resulting in a change to aspartic acid at position 752 of the viral DNA polymerase. Therefore, these strains were classified as horse neuropathogenic strains. Lastly, a phylogenetic tree was constructed using the partial ORF68 nucleotide sequences, showing that the identified donkey EHV-1 strain and the EHV-1 strain found in aborted Yili horses in China comprised a novel independent VIII group.
CONCLUSION
This study showed the first isolation and identification of EHV-1 as an etiological agent of abortions in donkeys. Further analysis of the ORF33, ORF30, and ORF68 sequences indicated that the donkey EHV-1 contained the neuropathogenic genotype of strains in the VIII group. It is thus important to be aware of EHV-1 infection in the donkey population, even though the virus has only been identified in donkey abortions in China.
Topics: Animals; Equidae; Herpesvirus 1, Equid; China; Phylogeny; Herpesviridae Infections; Lung; Aborted Fetus; Female; DNA, Viral; Open Reading Frames; Sequence Analysis, DNA; Pregnancy; Polymerase Chain Reaction
PubMed: 38802935
DOI: 10.1186/s12985-024-02390-2 -
One Health (Amsterdam, Netherlands) Jun 2024Peru was one of the most affected countries during the COVID-19 pandemic. Moreover, multiple other viral diseases (enteric, respiratory, bloodborne, and vector-borne)...
Peru was one of the most affected countries during the COVID-19 pandemic. Moreover, multiple other viral diseases (enteric, respiratory, bloodborne, and vector-borne) are endemic and rising. According to Peru's Ministry of Health, various health facilities in the country were reallocated for the COVID-19 pandemic, thereby leading to reduced action to curb other diseases. Many viral diseases in the area are under-reported and not recognized. The One Health approach, in addition to clinical testing, incorporates environmental surveillance for detection of infectious disease outbreaks. The purpose of this work is to use a screening tool that is based on molecular methods, high throughput sequencing and bioinformatics analysis of wastewater samples to identify virus-related diseases circulating in Trujillo-Peru. To demonstrate the effectiveness of the tool, we collected nine untreated wastewater samples from the Covicorti wastewater utility in Trujillo-Peru on October 22, 2022. High throughput metagenomic sequencing followed by bioinformatic analysis was used to assess the viral diversity of the samples. Our results revealed the presence of sequences associated with multiple human and zoonotic viruses including Orthopoxvirus, Hepatovirus, Rhadinovirus, Parechovirus, Mamastrovirus, Enterovirus, Varicellovirus, Norovirus, Kobuvirus, Bocaparvovirus, Simplexvirus, Spumavirus, Orthohepevirus, Cardiovirus, Molliscipoxvirus, Salivirus, Parapoxvirus, Gammaretrovirus, Alphavirus, Lymphocryptovirus, Erythroparvovirus, Sapovirus, Cosavirus, Deltaretrovirus, Roseolovirus, Flavivirus, Betacoronavirus, Rubivirus, Lentivirus, Betapolyomavirus, Rotavirus, Hepacivirus, Alphacoronavirus, Mastadenovirus, Cytomegalovirus and Alphapapillomavirus. For confirmation purposes, we tested the samples for the presence of selective viruses belonging to the genera detected above. PCR based molecular methods confirmed the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), monkeypox virus (MPXV), noroviruses GI and GII (NoVGI and NoVGII), and rotavirus A (RoA) in our samples. Furthermore, publicly available clinical data for selected viruses confirm our findings. Wastewater or other environmental media surveillance, combined with bioinformatics methods, has the potential to serve as a systematic screening tool for the identification of human or zoonotic viruses that may cause disease. The results of this method can guide further clinical surveillance efforts and allocation of resources. Incorporation of this bioinformatic-based screening tool by public health officials in Peru and other Latin American countries will help manage endemic and emerging diseases that could save human lives and resources.
PubMed: 38798735
DOI: 10.1016/j.onehlt.2024.100756 -
Viruses May 2024Equid herpesvirus 4 (EHV-4) is a common respiratory pathogen in horses. It sporadically induces abortion or neonatal death. Although its contribution in neurological...
Equid herpesvirus 4 (EHV-4) is a common respiratory pathogen in horses. It sporadically induces abortion or neonatal death. Although its contribution in neurological disorders is not clearly demonstrated, there is a strong suspicion of its involvement. Despite preventive treatments using vaccines against EHV-1/EHV-4, the resurgence of alpha-EHV infection still constitutes an important threat to the horse industry. Yet very few studies have been conducted on the search for antiviral molecules against EHV-4. A screening of 42 antiviral compounds was performed in vitro on equine fibroblast cells infected with the EHV-4 405/76 reference strain (VR2230). The formation of cytopathic effects was monitored by real-time cell analysis (RTCA), and the viral load was quantified by quantitative PCR. Aciclovir, the most widely used antiviral against alpha-herpesviruses in vivo, does not appear to be effective against EHV-4 in vitro. Potential antiviral activities were confirmed for eight molecules (idoxuridine, vidarabine, pritelivir, cidofovir, valganciclovir, ganciclovir, aphidicolin, and decitabine). Decitabine demonstrates the highest efficacy against EHV-4 in vitro. Transcriptomic analysis revealed the up-regulation of various genes implicated in interferon (IFN) response, suggesting that decitabine triggers the immune antiviral pathway.
Topics: Animals; Antiviral Agents; Horses; Decitabine; Immunity, Innate; Herpesvirus 4, Equid; Fibroblasts; Herpesviridae Infections; Horse Diseases; Viral Load; Cell Line; Virus Replication; Drug Evaluation, Preclinical
PubMed: 38793627
DOI: 10.3390/v16050746