{"title":"Preferential cleavage of the coronavirus defective viral genome by cellular endoribonuclease with characteristics of RNase L.","authors":"Ching-Hung Lin, Hsuan-Yung Lin, Chun-Chun Yang, Hsuan-Wei Hsu, Feng-Cheng Hsieh, Cheng-Yao Yang, Hung-Yi Wu","doi":"10.1186/s12985-024-02549-x","DOIUrl":"https://doi.org/10.1186/s12985-024-02549-x","url":null,"abstract":"<p><p>In testing whether coronavirus defective viral genome 12.7 (DVG12.7) with transcription regulating sequence (TRS) can synthesize subgenomic mRNA (sgmRNA) in coronavirus-infected cells, it was unexpectedly found by Northern blot assay that not only sgmRNA (designated sgmDVG 12.7) but also an RNA fragment with a size less than sgmDVG 12.7 was identified. A subsequent study demonstrated that the identified RNA fragment (designated clvDVG) was a cleaved RNA product originating from DVG12.7, and the cleaved sites were located in the loop region of stem‒loop structure and after UU and UA dinucleotides. clvDVG was also identified in mock-infected HRT-18 cells transfected with DVG12.7 transcript, indicating that cellular endoribonuclease is responsible for the cleavage. In addition, the sequence and structure surrounding the cleavage sites can affect the cleavage efficiency of DVG12.7. The cleavage features are therefore consistent with the general criteria for RNA cleavage by cellular RNase L. Furthermore, both the cleavage of rRNA and the synthesis of clvDVG were also identified in A549 cells. Because (i) the cleavage sites occurred predominantly after single-stranded UA and UU dinucleotides, (ii) the sequence and structure surrounding the cleavage sites affected the cleavage efficiency, (iii) the cleavage of rRNA is an index of the activation of RNase L, and (iv) the cleavage of both rRNA and DVG12.7 was identified in A549 cells, the results together indicated that the preferential cleavage of DVG12.7 is correlated with cellular endoribonuclease with the characteristics of RNase L and such cleavage features have not been previously characterized in coronaviruses.</p>","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Virology JournalPub Date : 2024-10-29DOI: 10.1186/s12985-024-02547-z
Saeed Tajik, Ali Vasheghani Farahani, Omid Salahi Ardekani, Saba Seyedi, Zahra Tayebi, Mostafa Kami, Faezeh Aghaei, Tahmine Mohammad Hosseini, Mohammad Mahdi Khosravi Nia, Roben Soheili, Arash Letafati
{"title":"Zika virus tropism and pathogenesis: understanding clinical impacts and transmission dynamics.","authors":"Saeed Tajik, Ali Vasheghani Farahani, Omid Salahi Ardekani, Saba Seyedi, Zahra Tayebi, Mostafa Kami, Faezeh Aghaei, Tahmine Mohammad Hosseini, Mohammad Mahdi Khosravi Nia, Roben Soheili, Arash Letafati","doi":"10.1186/s12985-024-02547-z","DOIUrl":"10.1186/s12985-024-02547-z","url":null,"abstract":"<p><p>The Zika virus (ZIKV) is classified within the Flavivirus genus of the Flaviviridae family and is categorized as an arbovirus. The virus was initially identified in a rhesus monkey in Uganda in 1947 and later in a human in Nigeria in 1952. Since 2007, the prevalence of the virus has been on the rise, culminating in a major outbreak in the United States (US) in 2015. During this outbreak, the adult population was severely impacted, experiencing a range of symptoms, including organ failure, microcephaly, fetal death, and Guillain-Barré syndrome (GBS). Additionally, skin rash, limb swelling, fever, headache, and heightened sensitivity are found in most adults with Zika syndrome. Although the virus can be transmitted through blood, vertical transmission from mother to child, and sexual contact, the primary way of transmission of the virus is through the Aedes mosquito. Cells such as neurons, macrophages, peripheral dendritic cells, and placental cells are among the target cells that the virus can infect. The TAM AXL receptor plays a crucial role in infection. After the virus enters the body through the bloodstream, it spreads in the body with a latent period of 3 to 12 days. Currently, there is no specific treatment or publicly available vaccine for the ZIKV. Limited laboratory testing has been conducted, and existing drugs originally designed for other pathogens have been repurposed for treatment. Given the Aedes mosquito's role as a vector and the wide geographical impact of the virus, this study aims to comprehensively investigate Zika's pathogenesis and clinical symptoms based on existing knowledge and research. By doing so, we seek to enhance our understanding of the virus and inform future prevention and treatment strategies.</p>","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11523830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Virology JournalPub Date : 2024-10-29DOI: 10.1186/s12985-024-02481-0
Sten Vermund, Maggie Bartlett
{"title":"Editorial: Charting a united health frontier to end pandemics.","authors":"Sten Vermund, Maggie Bartlett","doi":"10.1186/s12985-024-02481-0","DOIUrl":"10.1186/s12985-024-02481-0","url":null,"abstract":"","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11523657/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Virology JournalPub Date : 2024-10-28DOI: 10.1186/s12985-024-02523-7
Qi Xin, Xiao Liang, Jin Yang, Xiaorui Wang, Fang Hu, Meng Jiang, Yijia Liu, Jin Gong, Yiwen Pan, Lijuan Liu, Jiao Xu, Yuxin Cui, Hongyu Qin, Han Bai, Yixin Li, Junpeng Ma, Chengsheng Zhang, Bingyin Shi
{"title":"Metabolomic alterations in the plasma of patients with various clinical manifestations of COVID-19.","authors":"Qi Xin, Xiao Liang, Jin Yang, Xiaorui Wang, Fang Hu, Meng Jiang, Yijia Liu, Jin Gong, Yiwen Pan, Lijuan Liu, Jiao Xu, Yuxin Cui, Hongyu Qin, Han Bai, Yixin Li, Junpeng Ma, Chengsheng Zhang, Bingyin Shi","doi":"10.1186/s12985-024-02523-7","DOIUrl":"10.1186/s12985-024-02523-7","url":null,"abstract":"<p><strong>Background: </strong>The metabolomic profiles of individuals with different clinical manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have not been clearly characterized.</p><p><strong>Methods: </strong>We performed metabolomics analysis of 166 individuals, including 62 healthy controls, 16 individuals with asymptomatic SARS-CoV-2 infection, and 88 patients with moderate (n = 42) and severe (n = 46) symptomatic 2019 coronavirus disease (COVID-19; 17 with short-term and 34 with long-term nucleic-acid test positivity). By examining differential expression, we identified candidate metabolites associated with different SARS-CoV-2 infection presentations. Functional and machine learning analyses were performed to explore the metabolites' functions and verify their candidacy as biomarkers.</p><p><strong>Results: </strong>A total of 417 metabolites were detected. We discovered 70 differentially expressed metabolites that may help differentiate asymptomatic infections from healthy controls and COVID-19 patients with different disease severity. Cyclamic acid and N-Acetylneuraminic Acid were identified to distinguish symptomatic infected patients and asymptomatic infected patients. Shikimic Acid, Glycyrrhetinic acid and 3-Hydroxybutyrate can supply significant insights for distinguishing short-term and long-term nucleic-acid test positivity.</p><p><strong>Conclusion: </strong>Metabolomic profiling may highlight novel biomarkers for the identification of individuals with asymptomatic SARS-CoV-2 infection and further our understanding of the molecular pathogenesis of COVID-19.</p>","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11520427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142523201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Virology JournalPub Date : 2024-10-28DOI: 10.1186/s12985-024-02542-4
Kaat Ramaekers, Els Keyaerts, Lieselot Houspie, Kurt Beuselinck, Marijke Reynders, Katrien Lagrou, Marc Van Ranst, Annabel Rector
{"title":"Epidemiology and genetic diversity of human respiratory syncytial virus in Belgium between 2011 and 2019.","authors":"Kaat Ramaekers, Els Keyaerts, Lieselot Houspie, Kurt Beuselinck, Marijke Reynders, Katrien Lagrou, Marc Van Ranst, Annabel Rector","doi":"10.1186/s12985-024-02542-4","DOIUrl":"10.1186/s12985-024-02542-4","url":null,"abstract":"<p><strong>Background: </strong>Human respiratory syncytial virus (HRSV) is worldwide one of the leading causes of acute respiratory tract infections in young children and the elderly population. Two distinct subtypes of HRSV (A and B) and a multitude of genotypes have been described. The laboratory of Clinical and Epidemiological Virology (KU Leuven/University Hospitals Leuven) has a long-standing history of HRSV surveillance in Belgium.</p><p><strong>Methods: </strong>In this study, the seasonal circulation of HRSV in Belgium was monitored during 8 consecutive seasons prior to the SARS-CoV-2 pandemic (2011-2012 until 2018-2019). By use of a multiplex quantitative real time PCR panel, 27,386 respiratory samples were tested for HRSV. Further subtyping and sequencing of the HRSV positive samples was performed by PCR and Sanger sequencing. The prevalence and positivity rate were estimated in 4 distinct age groups and the circulating strains of each subtype were situated in a global context and in reference to the described genotypes in literature.</p><p><strong>Results: </strong>HRSV circulated in Belgium in a yearly re-occurring pattern during the winter months and both HRSV subtypes co-circulated simultaneously. All HRSV-B strains contained the 60 nt duplication in the HVR2 region of the G gene. Strains of subtype HRSV-A with a 72 nt duplication in the HVR2 region were first observed during the 2011-2012 season and replaced all other circulating strains from 2014 to 2015 onwards.</p>","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11520483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142523198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Virology JournalPub Date : 2024-10-28DOI: 10.1186/s12985-024-02545-1
Maggie L Bartlett, Marcela Uhart
{"title":"Leveraging one health as a sentinel approach for pandemic resilience.","authors":"Maggie L Bartlett, Marcela Uhart","doi":"10.1186/s12985-024-02545-1","DOIUrl":"10.1186/s12985-024-02545-1","url":null,"abstract":"<p><p>The resurgence of H5N1 avian influenza highlights the urgent need for robust surveillance systems to detect zoonotic risks before they evolve into human-to-human transmission. The One Health approach-integrating human, animal, and environmental health-offers a comprehensive framework for addressing these challenges. H5N1, a highly pathogenic avian influenza virus, has caused significant mortality in avian populations and poses a serious threat to human health. While human cases are rare, alarming outbreaks in mammals, such as elephant seals with up to 96% mortality, emphasize the importance of early detection in animal populations. Traditional surveillance methods, which often focus solely on human cases, are reactive and may be too late to prevent widespread transmission. One Health enhances early warning systems by monitoring wildlife, livestock, and environmental samples, identifying viral spillover events at their source, and enabling timely interventions to contain the virus before it reaches human populations.</p>","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11520784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142523200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"First detection of D181 genotype of infectious bronchitis in poultry flocks of Morocco.","authors":"Mouahid Mohamed, Bidoudan Yassmina, Regragui Rim, El Kaouani Mouna, Fellahi Siham","doi":"10.1186/s12985-024-02539-z","DOIUrl":"10.1186/s12985-024-02539-z","url":null,"abstract":"<p><strong>Background: </strong>This paper reports the first pathological and molecular characterization of the novel variant of infectious bronchitis virus (IBV) D181 in poultry flocks in Morocco and Africa.</p><p><strong>Methods: </strong>The study includes six poultry farms, involving three flocks of layers aged between 28 and 67 weeks and three broiler flocks aged 27, 39 and 42 days from different regions of Morocco. In all affected layer flocks, a severe drop in egg production with poor eggshell quality was reported. Necropsy of dead birds was carried out, and samples of trachea, lungs, oviduct, ovaries, and kidneys were fixed in 10% neutral buffered formalin for histopathologic examinations, while other portions were stored at -20 °C for molecular analysis. Real time RT-qPCR for IBV gene group was performed, and IBV variants were identified. Partial S1 gene sequences were amplified by conventional RT-PCR, sequenced, and aligned for phylogenetic and amino acid similarity analysis.</p><p><strong>Results: </strong>Necropsy of dead birds revealed misshapen and hemorrhagic ovarian follicles with an edematous oviduct and severe reaction in the cecal tonsils. A caseous material accumulation in the sinus was noted in few birds. In contrast, the broiler flocks exhibited respiratory clinical signs such as difficulty in breathing, sneezing, tracheal rales, watery eyes and lethargy, associated with a decrease in feed consumption. Mortality in broiler ranged from 2 to 15%. Histopathological analysis of samples showed a lympho-plasmocytic inflammation in the oviduct, trachea, and lungs. Individual necrosis of epithelial cells, with sloughing of the bronchial epithelium and accumulation of desquamated cells with mucus in the airways, was observed in some birds. Partial S1 gene sequencing and phylogenetic analyses showed that the Moroccan strains were very closely related to D181 strains isolated in Dutch layers and breeders in 2018. Nucleotide sequence identities reached 90.9-95% with the Dutch isolates (strain CK/NL/D181/2018).</p><p><strong>Conclusion: </strong>Our sequencing results demonstrate for the first time that the D181 IBV genotype is circulating in Moroccan poultry. These findings justify permanent monitoring of circulating strains in order to appropriately adjust vaccination strategies to align with the evolving field situation.</p>","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11520396/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142523199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Asiatic acid inhibits HBV cccDNA transcription by promoting HBx degradation.","authors":"Ranran Li, Chunduo Wang, Kexin Xu, Zongzhu Zhan, Siyi He, Jihua Ren, Fan Li, Nana Tao, Zhihong Li, Zhen Yang, Haibo Yu","doi":"10.1186/s12985-024-02535-3","DOIUrl":"10.1186/s12985-024-02535-3","url":null,"abstract":"<p><strong>Background: </strong>Hepatitis B virus (HBV) infection is a persistent global public health problem, and curing for chronic hepatitis B (CHB) through the application of existing antiviral drugs is beset by numerous challenges. The viral protein HBx is a critical regulatory factor in the life cycle of HBV. Targeting HBx is a promising possibility for the development of novel therapeutic strategies.</p><p><strong>Methods: </strong>The Nano-Glo<sup>®</sup> HiBiT Lysis Detection System was used to screen the herbal monomer compound library for compounds that inhibit HBx expression. Western blotting was used to examine proteins expression. Southern blotting or Northern blotting were used to detect HBV DNA or HBV RNA. ELISA was performed to detect the HBsAg level. The effect of asiatic acid on HBV in vivo was investigated by using recombinant cccDNA mouse model.</p><p><strong>Results: </strong>Asiatic acid, an extract of Centella asiatica, significantly reduced the HBx level. Mechanistic studies demonstrated that asiatic acid may promote the degradation of HBx in an autophagy pathway-dependent manner. Subsequently, asiatic acid was found to reduce the amount of HBx bound to covalently closed circular DNA (cccDNA) microchromosomes, and repressive chromatin modifications then occurred, ultimately inhibiting cccDNA transcriptional activity. Moreover, in HBV-infected cells and a mouse model of persistent HBV infection, asiatic acid exhibited potent anti-HBV activity, as evidenced by decreased levels of HBV RNAs, HBV DNA and HBsAg.</p><p><strong>Conclusions: </strong>Asiatic acid was identified as a compound that targets HBx, revealing its potential for application as an anti-HBV agent.</p>","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11520515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142523197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Virology JournalPub Date : 2024-10-25DOI: 10.1186/s12985-024-02536-2
Dilceu Silveira Tolentino Júnior, Maryana Santos Vasconcelos Marques, Roberto Carlos de Oliveira
{"title":"Adapted Milwaukee protocol for rabies treatment in a Brazilian indigenous child: case report.","authors":"Dilceu Silveira Tolentino Júnior, Maryana Santos Vasconcelos Marques, Roberto Carlos de Oliveira","doi":"10.1186/s12985-024-02536-2","DOIUrl":"10.1186/s12985-024-02536-2","url":null,"abstract":"<p><strong>Background: </strong>This case report describes the treatment of a 12-year-old indigenous Brazilian girl from the Maxakali group with rabies using the adapted Milwaukee Protocol.</p><p><strong>Case presentation: </strong>The patient suffered a superficial bat bite on her right elbow, reported on April 5, 2022. Despite receiving immunoglobulin, a vaccine, and antiviral medications such as amantadine and sapropterin, the patient succumbed to the disease 25 days after hospital admission. The report highlights the inherent challenges in treating rabies due to the virus's neurotropic nature and the difficulties in delivering antiviral drugs to the central nervous system. The case underscores the need for early antiviral intervention and calls for more studies to validate and improve treatment protocols for rabies in vulnerable populations, particularly those with genetic and immunological susceptibilities like the Maxakali indigenous group.</p><p><strong>Conclusion: </strong>The findings suggest that while the Milwaukee Protocol offers some hope, significant obstacles remain in achieving successful outcomes in rabies cases.</p>","PeriodicalId":23616,"journal":{"name":"Virology Journal","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11515255/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}