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Viruses Jun 2024Viral integration within the host genome plays a pivotal role in carcinogenesis. Various disruptive mechanisms are involved, leading to genomic instability, mutations,...
Viral integration within the host genome plays a pivotal role in carcinogenesis. Various disruptive mechanisms are involved, leading to genomic instability, mutations, and DNA damage. With next-generation sequencing (NGS), we can now precisely identify viral and host genomic breakpoints and chimeric sequences, which are useful for integration site analysis. In this study, we evaluated a commercial hybrid capture NGS panel specifically designed for detecting three key viruses: HPV, HBV, and HIV-1. We also tested workflows for Viral Hybrid Capture (VHC) and Viral Integration Site (VIS) analysis, leveraging customized viral databases in CLC Microbial Genomics. By analyzing sequenced data from virally infected cancer cell lines (including SiHa, HeLa, CaSki, C-33A, DoTc2, 2A3, SCC154 for HPV; 3B2, SNU-182 for HBV; and ACH-2 for HIV-1), we precisely pinpointed viral integration sites. The workflow also highlighted disrupted and neighboring human genes that may play a crucial role in tumor development. Our results included informative virus-host read mappings, genomic breakpoints, and integration circular plots. These visual representations enhance our understanding of the integration process. In conclusion, our seamless end-to-end workflow bridges the gap in understanding viral contributions to cancer development, paving the way for improved diagnostics and treatment strategies.
Topics: Humans; Virus Integration; Hepatitis B virus; HIV-1; High-Throughput Nucleotide Sequencing; Workflow; Carcinogenesis; Genomics; Cell Line, Tumor; Papillomaviridae
PubMed: 38932267
DOI: 10.3390/v16060975 -
Viruses Jun 2024Cervical cancer, along with other sexual and reproductive health and rights (SRHR) conditions, poses a significant burden in the Kingdom of Saudi Arabia (KSA). Despite...
Cervical cancer, along with other sexual and reproductive health and rights (SRHR) conditions, poses a significant burden in the Kingdom of Saudi Arabia (KSA). Despite the availability of effective preventive methods such as vaccinations, particularly against the Human Papillomavirus (HPV), awareness about such preventive methods and HPV vaccination remains alarmingly low in the KSA, even with governmental effort and support. While many women are aware of the risks, the uptake of the HPV vaccine remains below 10% (7.6%) at the country level. This highlights the urgent need for Knowledge, Attitude, and Practice (KAP) at the community level to raise awareness, dispel misconceptions, and empower women to embrace vaccinations. Additionally, there is a need to revitalize the cancer registry system to better track and monitor cervical cancer cases. This short communication aims to map these barriers while identifying opportunities for impactful research. Drawing from the scientific literature, government reports, and expert insights, we highlight the challenges surrounding the tackling of HPV. By exploring diverse sources of knowledge, this paper not only highlights current obstacles but also proposes actionable solutions for future interventions.
Topics: Humans; Uterine Cervical Neoplasms; Papillomavirus Vaccines; Female; Papillomavirus Infections; Saudi Arabia; Health Knowledge, Attitudes, Practice; Vaccination; Patient Acceptance of Health Care; Papillomaviridae
PubMed: 38932266
DOI: 10.3390/v16060974 -
Viruses Jun 2024Pathogenic adenovirus (Ad) infections are widespread but typically mild and transient, except in the immunocompromised. As vectors for gene therapy, vaccine, and... (Review)
Review
Pathogenic adenovirus (Ad) infections are widespread but typically mild and transient, except in the immunocompromised. As vectors for gene therapy, vaccine, and oncology applications, Ad-based platforms offer advantages, including ease of genetic manipulation, scale of production, and well-established safety profiles, making them attractive tools for therapeutic development. However, the immune system often poses a significant challenge that must be overcome for adenovirus-based therapies to be truly efficacious. Both pre-existing anti-Ad immunity in the population as well as the rapid development of an immune response against engineered adenoviral vectors can have detrimental effects on the downstream impact of an adenovirus-based therapeutic. This review focuses on the different challenges posed, including pre-existing natural immunity and anti-vector immunity induced by a therapeutic, in the context of innate and adaptive immune responses. We summarise different approaches developed with the aim of tackling these problems, as well as their outcomes and potential future applications.
Topics: Humans; Adenoviridae; Genetic Vectors; Genetic Therapy; Adaptive Immunity; Animals; Immunity, Innate; Immune System; Adenoviridae Infections
PubMed: 38932265
DOI: 10.3390/v16060973 -
Viruses Jun 2024Illicit drug and alcohol abuse have significant negative consequences for individuals who inject drugs/use drugs (PWID/UDs), including decreased immune system function... (Review)
Review
Illicit drug and alcohol abuse have significant negative consequences for individuals who inject drugs/use drugs (PWID/UDs), including decreased immune system function and increased viral pathogenesis. PWID/UDs are at high risk of contracting or transmitting viral illnesses such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV). In South Africa, a dangerous drug-taking method known as "Bluetoothing" has emerged among nyaope users, whereby the users of this drug, after injecting, withdraw blood from their veins and then reinject it into another user. Hence, the transmission of blood-borne viruses (BBVs) is exacerbated by this "Bluetooth" practice among nyaope users. Moreover, several substances of abuse promote HIV, HBV, and HCV replication. With a specific focus on the nyaope drug, viral replication, and transmission, we address the important influence of abused addictive substances and polysubstance use in this review.
Topics: Humans; Substance-Related Disorders; South Africa; Hepatitis C; Hepatitis B; HIV Infections; Virus Replication; Illicit Drugs; Hepatitis B virus; Virus Diseases; Blood-Borne Infections; Hepacivirus; Substance Abuse, Intravenous
PubMed: 38932263
DOI: 10.3390/v16060971 -
Viruses Jun 2024Begomoviruses have emerged as destructive pathogens of crops, particularly in the tropics and subtropics, causing enormous economic losses and threatening food security.... (Review)
Review
Begomoviruses have emerged as destructive pathogens of crops, particularly in the tropics and subtropics, causing enormous economic losses and threatening food security. Epidemics caused by begomoviruses have even spread in regions and crops that were previously free from these viruses. The most seriously affected crops include cassava; cotton; grain legumes; and cucurbitaceous, malvaceous, and solanaceous vegetables. Alphasatellites, betasatellites, and deltasatellites are associated with the diseases caused by begomoviruses, but begomovirus-betasatellite complexes have played significant roles in the evolution of begomoviruses, causing widespread epidemics in many economically important crops throughout the world. This article provides an overview of the evolution, distribution, and approaches used by betasatellites in the suppression of host plant defense responses and increasing disease severity.
Topics: Begomovirus; Plant Diseases; Crops, Agricultural; Satellite Viruses; Evolution, Molecular; DNA, Satellite; Phylogeny
PubMed: 38932261
DOI: 10.3390/v16060970 -
Viruses Jun 2024Innate immunity, the first line of host defense against viral infections, recognizes viral components through different pattern-recognition receptors. Nucleic acids... (Review)
Review
Innate immunity, the first line of host defense against viral infections, recognizes viral components through different pattern-recognition receptors. Nucleic acids derived from viruses are mainly recognized by Toll-like receptors, nucleotide-binding domain leucine-rich repeat-containing receptors, absent in melanoma 2-like receptors, and cytosolic DNA sensors (e.g., Z-DNA-binding protein 1 and cyclic GMP-AMP synthase). Different types of nucleic acid sensors can recognize specific viruses due to their unique structures. PANoptosis is a unique form of inflammatory cell death pathway that is triggered by innate immune sensors and driven by caspases and receptor-interacting serine/threonine kinases through PANoptosome complexes. Nucleic acid sensors (e.g., Z-DNA-binding protein 1 and absent in melanoma 2) not only detect viruses, but also mediate PANoptosis through providing scaffold for the assembly of PANoptosomes. This review summarizes the structures of different nucleic acid sensors, discusses their roles in viral infections by driving PANoptosis, and highlights the crosstalk between different nucleic acid sensors. It also underscores the promising prospect of manipulating nucleic acid sensors as a therapeutic approach for viral infections.
Topics: Humans; Virus Diseases; Immunity, Innate; Nucleic Acids; Animals; DNA-Binding Proteins; Viruses; Receptors, Pattern Recognition; RNA-Binding Proteins
PubMed: 38932258
DOI: 10.3390/v16060966 -
Viruses Jun 2024Quantification of Torquetenovirus (TTV) viremia is becoming important for evaluating the status of the immune system in solid organ transplant recipients, monitoring the...
Quantification of Torquetenovirus (TTV) viremia is becoming important for evaluating the status of the immune system in solid organ transplant recipients, monitoring the appearance of post-transplant complications, and controlling the efficacy of maintenance immunosuppressive therapy. Thus, diagnostic approaches able to scale up TTV quantification are needed. Here, we report on the development and validation of a real-time PCR assay for TTV quantification on the Hologic Panther Fusion System by utilizing its open-access channel. The manual real-time PCR previously developed in our laboratories was optimized to detect TTV DNA on the Hologic Panther Fusion System. The assay was validated using clinical samples. The automated TTV assay has a limit of detection of 1.6 log copies per ml of serum. Using 112 samples previously tested via manual real-time PCR, the concordance in TTV detection was 93% between the assays. When the TTV levels were compared, the overall agreement between the methods, as assessed using Passing-Bablok linear regression and Bland-Altman analyses, was excellent. In summary, we validated a highly sensitive and accurate method for the diagnostic use of TTV quantification on a fully automated Hologic Panther Fusion System. This will greatly improve the turnaround time for TTV testing and better support the laboratory diagnosis of this new viral biomarker.
Topics: Real-Time Polymerase Chain Reaction; Viremia; Humans; Viral Load; DNA Virus Infections; Sensitivity and Specificity; Torque teno virus; DNA, Viral; Limit of Detection; Reproducibility of Results; Automation, Laboratory
PubMed: 38932255
DOI: 10.3390/v16060963 -
Viruses Jun 2024Influenza A virus (IAV) infections in swine are usually subclinical, but they can reach high morbidity rates. The mortality rate is normally low. In this study, six...
Spontaneous Lethal Outbreak of Influenza A Virus Infection in Vaccinated Sows on Two Farms Suggesting the Occurrence of Vaccine-Associated Enhanced Respiratory Disease with Eosinophilic Lung Pathology.
Influenza A virus (IAV) infections in swine are usually subclinical, but they can reach high morbidity rates. The mortality rate is normally low. In this study, six vaccinated, spontaneously deceased sows revealed IAV infection and enhanced neutrophilic bronchopneumonia with unexpectedly large numbers of infiltrating eosinophils. The purpose of this study was to characterize these lung lesions with special emphasis on the phenotypes of inflammatory cells, the presence of eosinophilic peroxidase (EPO), and neutrophil extracellular traps (NETs). The number of Sirius red-stained eosinophils was significantly higher in the lungs of IAV-infected sows compared to healthy pigs, indicating a migration of eosinophils from blood vessels into the lung tissue stimulated by IAV infection. The detection of intra- and extracellular EPO in the lungs suggests its contribution to pulmonary damage. The presence of CD3 T lymphocytes, CD20 B lymphocytes, and Iba-1 macrophages indicates the involvement of cell-mediated immune responses in disease progression. Furthermore, high numbers of myeloperoxidase-positive cells were detected. However, DNA-histone-1 complexes were reduced in IAV-infected sows, leading to the hypothesis that NETs are not formed in the IAV-infected sows. In conclusion, our findings in the lungs of IAV-infected vaccinated sows suggest the presence of so far unreported field cases of vaccine-associated enhanced respiratory disease.
Topics: Animals; Swine; Lung; Swine Diseases; Orthomyxoviridae Infections; Female; Influenza Vaccines; Influenza A virus; Disease Outbreaks; Eosinophils; Extracellular Traps; Vaccination; Eosinophil Peroxidase
PubMed: 38932247
DOI: 10.3390/v16060955 -
Viruses Jun 2024Despite the availability of a vaccine against hepatitis B virus (HBV), this infection still causes public health problems, particularly in susceptible populations. In...
Despite the availability of a vaccine against hepatitis B virus (HBV), this infection still causes public health problems, particularly in susceptible populations. In Portugal, universal free vaccination started in 1994, and most HBV infections are diagnosed in immigrants from high-prevalence countries. Our aim was to assess the pattern of HBV genotypes/subgenotypes in samples collected between 2017 and 2021 from a convenience sample of 70 infected residents in Portugal. The HBV pol/HBsAg region was amplified and sequenced, allowing the analysis of RT sequences submitted to phylogenetic analysis and mutations assessment. A total of 37.1% of samples were from native Portuguese, aged 25-53 years (mean: 36.7 years), and the remaining samples were from individuals born outside of Portugal. A high diversity of HBV was identified: subgenotypes A1-A3 in 41.0% (16/39); D1, D3, and D4 in 30.7% (12/39); E in 23.1% (9/39); and F4 in 2.6% (1/39). Besides genotypes A and D, Portuguese were also infected with genotypes E and F, which are prevalent in Africa and South America, respectively. Resistance mutations in RT sequences were not found. The findings provide valuable insights for updating the HBV molecular epidemiology in Portugal. However, successful strategies to prevent and control the infection are still needed in the country, especially among susceptible and vulnerable populations.
Topics: Humans; Hepatitis B virus; Genotype; Adult; Middle Aged; Phylogeny; Hepatitis B; Female; Male; Portugal; Vaccination; Hepatitis B Vaccines; Mutation; Genetic Variation; Hepatitis B Surface Antigens; DNA, Viral; Young Adult
PubMed: 38932246
DOI: 10.3390/v16060954 -
Viruses Jun 2024Respiratory viruses significantly impact global morbidity and mortality, causing more disease in humans than any other infectious agent. Beyond pathogens, various...
BACKGROUND
Respiratory viruses significantly impact global morbidity and mortality, causing more disease in humans than any other infectious agent. Beyond pathogens, various viruses and bacteria colonize the respiratory tract without causing disease, potentially influencing respiratory diseases' pathogenesis. Nevertheless, our understanding of respiratory microbiota is limited by technical constraints, predominantly focusing on bacteria and neglecting crucial populations like viruses. Despite recent efforts to improve our understanding of viral diversity in the human body, our knowledge of viral diversity associated with the human respiratory tract remains limited.
METHODS
Following a comprehensive search in bibliographic and sequencing data repositories using keyword terms, we retrieved shotgun metagenomic data from public repositories (n = 85). After manual curation, sequencing data files from 43 studies were analyzed using EVEREST (pipEline for Viral assEmbly and chaRactEriSaTion). Complete and high-quality contigs were further assessed for genomic and taxonomic characterization.
RESULTS
Viral contigs were obtained from 194 out of the 868 FASTQ files processed through EVEREST. Of the 1842 contigs that were quality assessed, 8% (n = 146) were classified as complete/high-quality genomes. Most of the identified viral contigs were taxonomically classified as bacteriophages, with taxonomic resolution ranging from the superkingdom level down to the species level. Captured contigs were spread across 25 putative families and varied between RNA and DNA viruses, including previously uncharacterized viral genomes. Of note, airway samples also contained virus(es) characteristic of the human gastrointestinal tract, which have not been previously described as part of the lung virome. Additionally, by performing a meta-analysis of the integrated datasets, ecological trends within viral populations linked to human disease states and their biogeographical distribution along the respiratory tract were observed.
CONCLUSION
By leveraging publicly available repositories of shotgun metagenomic data, the present study provides new insights into viral genomes associated with specimens from the human respiratory tract across different disease spectra. Further studies are required to validate our findings and evaluate the potential impact of these viral communities on respiratory tract physiology.
Topics: Humans; Metagenomics; Virome; Genome, Viral; Respiratory System; Viruses; Metagenome; Computer Simulation; Phylogeny; Computational Biology; Microbiota; Bacteriophages
PubMed: 38932245
DOI: 10.3390/v16060953