Frontiers in virology最新文献

{"title":"Emergence of enterovirus D68 in a Norwegian paediatric population 2012-2022","authors":"Elisabeth Toverud Landaas, Ingvild Klundby, Per Kristian Knudsen, Anne-Marte Bakken Kran, Susanne Dudman, Andreas Lind, Mona Holberg-Petersen","doi":"10.3389/fviro.2024.1358963","DOIUrl":"https://doi.org/10.3389/fviro.2024.1358963","url":null,"abstract":"<sec><title>Background</title><p>Enterovirus D68 (EV-D68) primarily causes respiratory infection, occasionally manifesting with neurological symptoms. Outbreak reports have been published from various countries including Norway, but a longitudinal study on EV-D68 prevalence in Northern Europe is lacking.</p></sec><sec><title>Methods</title><p>Respiratory samples from children ≤14 years received at Oslo University Hospital in the years 2012-2022 were examined for EV-D68. Samples from 2012-2015 were retrospectively screened using a semi-specific RT-PCR, with positive samples confirmed by an EV-D68 specific RT-PCR. Samples from 2016-2022 underwent routine diagnostics with the EV-D68 specific RT-PCR.</p></sec><sec><title>Results</title><p>Among the 22,911 samples tested, EV-D68 was detected in 338 samples (324 patients). Most EV-D68 cases occurred in August to December. The highest detection rate was recorded in 2014, 2016 and 2022 (6.0%, 7.8% and 6.6% of samples from August-December). Lower frequencies were observed in 2018 and 2019 (1.0% and 2.4%), and in the years before the 2014 outbreak (2012: 1.3%, 2013: 0.8%). Few cases were identified in 2020-2021. Children aged 0-1 years accounted for 40%, and 0-4 years for 78%, of the EV-D68 positive patients. Most of the patients with EV-D68 (83%) were hospitalised.</p></sec><sec><title>Discussion</title><p>Also in Norway, EV-D68 has caused outbreaks with significant disease burden, especially among the youngest children. The detection rate varies, with a trend towards biennial outbreaks, except for low numbers in 2018 and during the COVID-19 restrictions (2020-2021). Due to its potential for severe respiratory illness and significant neurological complications, conducting EV-D68 testing is essential both for diagnosing clinically suspected cases, and for monitoring the disease burden.</p></sec>","PeriodicalId":73114,"journal":{"name":"Frontiers in virology","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139977785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enterovirus-D68 – a reemerging non-polio enterovirus that causes severe respiratory and neurological disease in children","authors":"Cassandra S. Grizer, Kevin Messacar, Joseph J. Mattapallil","doi":"10.3389/fviro.2024.1328457","DOIUrl":"https://doi.org/10.3389/fviro.2024.1328457","url":null,"abstract":"<p>The past decade has seen the global reemergence and rapid spread of enterovirus D68 (EV-D68), a respiratory pathogen that causes severe respiratory illness and paralysis in children. EV-D68 was first isolated in 1962 from children with pneumonia. Sporadic cases and small outbreaks have been reported since then with a major respiratory disease outbreak in 2014 associated with an increased number of children diagnosed with polio-like paralysis. From 2014-2018, major outbreaks were reported every other year in a biennial pattern with &gt; 90% of the cases occurring in children under the age of 16. With the outbreak of SARS-CoV-2 and the subsequent COVID-19 pandemic, there was a significant decrease in the prevalence EV-D68 cases along with other respiratory diseases. However, since the relaxation of pandemic social distancing protocols and masking mandates the number of EV-D68 cases have begun to rise again-culminating in another outbreak in 2022. Here we review the virology, pathogenesis, and the immune response to EV-D68, and discuss the epidemiology of EV-D68 infections and the divergence of contemporary strains from historical strains. Finally, we highlight some of the key challenges in the field that remain to be addressed.</p>","PeriodicalId":73114,"journal":{"name":"Frontiers in virology","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139773184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enterovirus D68 circulation between 2014 and 2022 in Slovenian children","authors":"Tina Uršič, Monika Jevšnik Virant, Rok Kogoj, Uros Krivec, Joanna Prusnik, Minca Mramor, Sara Lovšin, Miroslav Petrovec","doi":"10.3389/fviro.2024.1335752","DOIUrl":"https://doi.org/10.3389/fviro.2024.1335752","url":null,"abstract":"<sec><title>Introduction</title><p>Enterovirus D68 (EV-D68) belongs to the <italic>Picornaviridae</italic> family, genus <italic>Enterovirus</italic>. It is mostly known as a respiratory virus causing upper and lower respiratory tract infections, but it is also rarely associated with a variety of central nervous system complications, with acute flaccid myelitis being reported most frequently. This study assesses the incidence, seasonality, clinical presentation, and molecular epidemiology of the EV-D68 strain in EV-positive children hospitalized between 2014 and 2022 at the largest pediatric medical center in Slovenia.</p></sec><sec><title>Methods</title><p>EV-D68 was detected using specific qRT-PCR, whereas partial VP1 sequences were obtained with Sanger sequencing, and further analyzed using the software CLC Main Workbench version 7 and MEGA version X.</p></sec><sec><title>Results</title><p>EV-D68 was detected in 154 out of 1,145 (13.4%) EV-positive children. In the two epidemic years, 2014 and 2016, EV-D68 was most frequently detected in the summer and early autumn, peaking in September. The median age of EV-D68–infected children was 3 years (IQR 1–3 years), with a female: male ratio of 1:1.17. Rhinorrhea was present in 74.0% of children, respiratory distress in 82.5%, and hypoxemia requiring supplemental oxygen in 44.1%. Out of 154 patients, 80.0% were hospitalized, with a median stay of 2 days (IQR 1–3 days). Lower respiratory tract infection was observed in 89.0% of EV-D68–positive patients, with bronchitis and bronchiolitis being most frequently diagnosed. No central nervous system manifestations of EV-D68 infection were observed in the study cohort. Phylogenetic analysis of partial VP1 sequences of EV-D68 revealed close similarity to the EV-D68 variants that were circulating in other European countries in these years.</p></sec><sec><title>Discussion</title><p>Slovenia faced two EV-D68 epidemics in 2014 and 2016; however, after 2016 only nine more cases were detected until the end of the study period. Based on the results of this study, EV-D68 was a frequent cause of lower respiratory tract infection among EV-positive patients. However, none of the patients we studied needed ICU treatment, and none developed acute flaccid paralysis. Our results indicate that EV-D68 is not present constantly, so additional monitoring studies should be conducted in the future to better understand the implications of this EV type in human disease.</p></sec>","PeriodicalId":73114,"journal":{"name":"Frontiers in virology","volume":"76 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139515061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of Parvovirus B19 persistence and reactivation in human heart layers","authors":"Ashwin Badrinath, Anais Gardere, Samantha L. Palermo, Kenneth S. Campbell, Anna Kloc","doi":"10.3389/fviro.2024.1304779","DOIUrl":"https://doi.org/10.3389/fviro.2024.1304779","url":null,"abstract":"<p>Heart disease is the leading cause of death worldwide. Myocarditis, or inflammation of the cardiac muscle, is estimated to cause up to 1.5 million cases annually, with viral infection being the most common disease culprit. Past studies have shown that Parvovirus B19 is routinely detected in endomyocardial biopsies. This virus has been linked to acute heart inflammation, which can cause cardiac muscle damage. However, because Parvovirus B19 can be found in the heart tissues in the absence of disease symptoms, it is unclear if the long-term presence of the virus contributes to, or initiates, heart disease. Here, we utilized a PCR-based detection assay to assess the presence of the B19V genome and its mRNA intermediates in human heart tissues. The analysis was carried out in three heart layers derived from one individual: epicardium, endocardium and myocardium. We showed the Parvovirus B19 genome presence variability in different heart layers. Similarly, viral transcriptional activity, assessed by the mRNA presence, was detected only in a few of the analyzed samples. Our results suggest that localized sites of Parvovirus B19 infection may exist within individual heart layers, which may have implication for the cardiac muscle inflammation.</p>","PeriodicalId":73114,"journal":{"name":"Frontiers in virology","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139754276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"APOBEC3D excludes APOBEC3F from HIV-1 virions by competitive binding of RNA","authors":"Shreoshri Bhattacharjee, Amit Gaba, Linda Chelico","doi":"10.3389/fviro.2024.1343037","DOIUrl":"https://doi.org/10.3389/fviro.2024.1343037","url":null,"abstract":"<p>The human family of APOBEC3 enzymes are primarily studied as single-stranded DNA deoxycytidine deaminases that act as host restriction factors for a number of viruses and retroelements. The deamination of deoxycytidine to deoxyuridine causes inactivating mutations in target DNA and the nucleic acid binding ability may also cause deamination independent restriction. There are seven APOBEC3 enzymes in humans, named A-H, excluding E, each of which has restriction activity against a subset of viruses or retroelements. There are primarily four, APOBEC3D, APOBEC3F, APOBEC3G, and APOBEC3H that have been found to restrict replication of HIV-1, however their restriction activity varies and they have primarily been studied individually despite co-expression in the cells that HIV-1 infects. It is known that APOBEC3F hetero-oligomerizes with APOBEC3G and APOBEC3H and that this influences host restriction outcomes during HIV-1 infection in tissue culture. Here, we examined if APOBEC3F interacts with APOBEC3D and the functional outcomes. We found that <italic>APOBEC3D</italic> mRNA expression was similar to or higher than <italic>APOBEC3F</italic> mRNA in multiple donors, suggesting that the proteins would be co-expressed, allowing for interactions to occur. We determined that APOBEC3F and APOBEC3D interacted primarily through an RNA intermediate; however, this interaction resulted in APOBEC3D competitively excluding APOBEC3F from virions. Although HIV-1 restriction still occurred when APOBEC3F and APOBEC3D were co-expressed, it was due to primarily APOBEC3D-mediated deamination-independent restriction. The APOBEC3D-mediated exclusion of APOBEC3F from HIV-1 encapsidation could be recapitulated <italic>in vitro</italic> through RNA capture experiments in which APOBEC3D decreased or abrogated the ability of APOBEC3F to bind to HIV-1 protease or 5’UTR RNA, respectively. Overall, the data suggest that there are mechanisms at the protein level that segregate APOBEC3s into different virus particles.</p>","PeriodicalId":73114,"journal":{"name":"Frontiers in virology","volume":"123 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Seroprevalence of dengue, yellow fever, and related flaviviruses among the rural human population in Nguruman and Kerio Valley, Kenya.","authors":"Mercy Hokah Kibathi, Edith Chepkorir, Sepha Nyatichi Mabeya, David P Tchouassi, Rosemary Sang","doi":"10.3389/fviro.2024.1459021","DOIUrl":"10.3389/fviro.2024.1459021","url":null,"abstract":"<p><strong>Background: </strong>Yellow fever virus (YFV) and dengue virus (DENV) are among the major re-emerging arboviruses that pose a significant threat to public health. Their associated burden and prevalence can be substantially underestimated due to insufficient surveillance and inadequate diagnosis. This study aimed to determine evidence of dengue, yellow and related flaviviruses circulation among the rural human populations residing in Nguruman (Kajiado County) and Kerio Valley (Baringo County), two dryland ecosystems in the Kenyan Rift Valley.</p><p><strong>Methods: </strong>Serum samples obtained from febrile patients between 5 and 85 years through a hospital-based cross-sectional survey from July 2020 - May 2023, were screened for neutralizing antibodies to YFV, DENV-2 and related flaviviruses, West Nile virus (WNV) and Zika virus (ZIKV) via Plaque reduction neutralization test (PRNT). The study sites and important demographic characteristics were obtained using a structural questionnaire and the data analyzed and seroprevalence compared. A multinomial logistic regression model was done to predict risk for each of the most prevalent viruses with covariates; age, gender, and occupation.</p><p><strong>Results: </strong>Overall, 54.5% (50.1-59.0% 95% confidence interval (CI) of the samples tested positive for at least one of the four Flaviviruses. The percentage was significantly higher in Kerio Valley (64.34%, 184/286) than in Nguruman (40.2%, 78/194) (P<0.0001). YFV had the highest prevalence, followed by WNV (16.25%), ZIKV (5.2%), and DENV-2 (1%). Kerio Valley had a significantly higher YFV seroprevalence (51%) than Nguruman (6%) (P<0.0001), while DENV-2 was observed only in Nguruman with a low seropositivity of 2%. In contrast to Nguruman, where seropositivity rates were higher in males at 47.47% (P=0.049), in Kerio Valley, females showed considerably higher viral seropositivity at 60.82% than males (P<0001).</p><p><strong>Conclusion: </strong>The study suggests that there is significant circulation of Flaviviruses in both regions, posing a public health risk, that could potentially contribute to clinical disease. However, seropositivity rates vary for each specific site. Furthermore, there could be a risk of YFV, WNV, and ZIKV transmission in both sites with DENV transmission specifically noted in Nguruman. The study findings inform direct cost-effective actions (such as YF vaccines) and precise surveillance data of vector populations for improved disease risk prediction.</p>","PeriodicalId":73114,"journal":{"name":"Frontiers in virology","volume":"4 ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12998444/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147488747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of the evolutionary and virological aspects of mutations in the receptor binding motif of the SARS-CoV-2 spike protein","authors":"Yuuka Masuda, H. Nasser, Jiří Zahradník, Shuya Mitoma, Ryo Shimizu, Kayoko Nagata, A. Takaori-Kondo, Gideon Schreiber, Kotaro Shirakawa, Akatsuki Saito, Terumasa Ikeda, Jumpei Ito, Kei Sato","doi":"10.3389/fviro.2023.1328229","DOIUrl":"https://doi.org/10.3389/fviro.2023.1328229","url":null,"abstract":"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has substantially diversified during the pandemic, resulting in the successive emergence of variants characterized by various mutations. It has been observed that several epidemic variants, including those classified as variants of concern, share mutations at four key residues (L452R, T478K, E484K, and N501Y) within the receptor binding motif (RBM) region of the spike protein. However, the processes through which these four specific RBM mutations were acquired during the evolution of SARS-CoV-2, as well as the degree to which they enhance viral fitness, remain unclear. Moreover, the effect of these mutations on the properties of the spike protein is not yet fully understood. In this study, we performed a comprehensive phylogenetic analysis and showed that the four RBM mutations have been convergently acquired across various lineages throughout the evolutionary history of SARS-CoV-2. We also found a specific pattern in the order of acquisition for some of these mutations. Additionally, our epidemic dynamic modeling demonstrated that acquiring these mutations leads to an increase in the effective reproduction number of the virus. Furthermore, we engineered mutant spike proteins with all feasible combinations of the four mutations, and examined their properties to uncover the influence that these mutations have on viral characteristics. Our results provide insights into the roles these four mutations play in shaping the viral characteristics, epidemic proliferation, and evolutionary pathway of SARS-CoV-2.","PeriodicalId":73114,"journal":{"name":"Frontiers in virology","volume":"31 16","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138946868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trends in the enterovirus surveillance in Oslo, Norway before and during the COVID-19 pandemic","authors":"Susanne Dudman, Ingvild Klundby, Joakim Øverbø, Sanela Numanovic, Mariann Nilsen, Andreas Lind, Mona Holberg-Petersen, Elisabeth Toverud Landaas","doi":"10.3389/fviro.2023.1343781","DOIUrl":"https://doi.org/10.3389/fviro.2023.1343781","url":null,"abstract":"<sec><title>Background</title><p>Enteroviruses have the potential to cause both high morbidity and mortality especially in children. High season in Norway is between August and November, but this seasonality was interrupted by the COVID-19 pandemic.</p></sec><sec><title>Methods</title><p>In this study, we describe the enterovirus surveillance in Norway before and during the COVID-19 pandemic including the years from the start of 2016 until the end of 2022. Screening of enterovirus was performed by both laboratory developed methods and FilmArray^® ME Panel. Relevant samples were typed, mostly by VP1 sequencing.</p></sec><sec><title>Results</title><p>Seventy-four percent of all cases occurred in infants under five years of age. A significant reduction in positive cases was observed during the peak years of the COVID-19 pandemic compared to the years before. Pre-pandemic, a wide range of types from all four enterovirus species were detected. During the years with COVID-19 infection control measures, significantly fewer enterovirus types were found along with a substantial reduction in the detection rate.</p></sec><sec><title>Conclusion</title><p>Enterovirus surveillance discovered a large amount of different types mainly affecting infants. The positivity rate was markedly reduced during the pandemic in 2020-2022 and fewer types occurred.</p></sec>","PeriodicalId":73114,"journal":{"name":"Frontiers in virology","volume":"58 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139396459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential susceptibility of human microglia HMC3 cells and brain microvascular endothelial HBEC-5i cells to Mayaro and Una virus infection","authors":"Dalkiria Campos, Madelaine Sugasti-Salazar, Patricia Valdés-Torres, Paola Elaine Galán-Jurado, Dalel Zegarra, José González-Santamaría","doi":"10.3389/fviro.2023.1325282","DOIUrl":"https://doi.org/10.3389/fviro.2023.1325282","url":null,"abstract":"<p>Mayaro (MAYV) and Una (UNAV) are emerging alphaviruses circulating in the Americas. Earlier reports have revealed that MAYV infects different human cell lines, including synovial and dermal fibroblasts, chondrocytes, osteoblasts, astrocytes and pericytes, as well as neural progenitor cells. In this study we evaluated the susceptibility of immortalized human microglia HMC3 cells and brain microvascular endothelial HBEC-5i cells to MAYV and UNAV infection. Cytopathic effects, cell viability, viral progeny yields, and the presence of E1 and nsP1 proteins in HMC3 and HBEC-5i cells infected with several MAYV or UNAV strains were assessed using an inverted microscope, MTT assay, plaque-forming assays, and immunofluorescence or Western blot, respectively. Finally, the expression of immune response genes was analyzed using RT-qPCR. MAYV and UNAV demonstrated strong cytopathic effects and significantly reduced cell viability in HMC3 cells. Moreover, the HMC3 cells were efficiently infected regardless of the virus strain tested, and E1 and nsP1 viral proteins were detected. In contrast, only MAYV appeared to infect HBEC-5i cells, and minimal effects on cell morphology or viability were observed. Furthermore, the MAYV titer and viral protein levels were substantially lower in the infected HBEC-5i cells when compared to those of the infected microglia cells. Finally, unlike UNAV, MAYV elicited a strong expression of specific interferon-stimulated genes in microglia cells, along with pro-inflammatory cytokines implicated in the immune response. Collectively, these findings demonstrate that MAYV and UNAV are capable of infecting relevant human brain cells.</p>","PeriodicalId":73114,"journal":{"name":"Frontiers in virology","volume":"79 1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139396220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Processing of the Hepatitis E virus ORF1 nonstructural polyprotein","authors":"Yogesh A. Karpe","doi":"10.3389/fviro.2023.1327745","DOIUrl":"https://doi.org/10.3389/fviro.2023.1327745","url":null,"abstract":"<p>Hepatitis E viruses (HEV) Open Reading Frame 1 (ORF1) encodes a non-structural polyprotein. In most positive-sense RNA viruses found in animals, this non-structural polyprotein is cleaved by viral protease or host protease. However, the mechanism behind the processing of HEV polyprotein remains one of the most controversial questions in HEV biology. The role of putative HEV protease in processing is difficult to demonstrate. Recent studies have questioned the existence of HEV protease and suggested that pORF1 lacks protease activity. Conversely, studies also suggested the role of host proteases involved in the blood coagulation cascade, like thrombin, in processing the HEV pORF1 polyprotein. In summary, recent studies support the notion that pORF1 lacks protease activity and host proteases are responsible for processing pORF1. The present review compiles a thorough overview of contentious research on HEV’s papain-like cysteine protease (PCP) and highlights recent advancements in the field. We aim to discuss the challenges and opportunities in the field to focus on further research.</p>","PeriodicalId":73114,"journal":{"name":"Frontiers in virology","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139101821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}