Benjamin Morgan, Eleanor A Lyons, Amanda Handley, Nada Bogdanovic-Sakran, Daniel Pavlic, Desiree Witte, Jonathan Mandolo, Ann Turner, Khuzwayo C Jere, Frances Justice, Darren Suryawijaya Ong, Rhian Bonnici, Karen Boniface, Celeste M Donato, Ashley Mpakiza, Anell Meyer, Naor Bar-Zeev, Miren Iturriza-Gomara, Nigel A Cunliffe, Margaret Danchin, Julie E Bines
High titres of rotavirus-specific maternal antibodies may contribute to lower rotavirus vaccine efficacy in low- and middle-income countries (LMICs). RV3-BB vaccine (G3P[6]) is based on a neonatal rotavirus strain that replicates well in the newborn gut in the presence of breast milk. This study investigated the association between maternal serum antibodies and vaccine response in infants administered the RV3-BB vaccine. Serum was collected antenatally from mothers of 561 infants enrolled in the RV3-BB Phase II study conducted in Blantyre, Malawi, and analysed for rotavirus-specific serum IgA and IgG antibodies using enzyme-linked immunosorbent assay. Infant vaccine take was defined as cumulative IgA seroconversion (≥3 fold increase) and/or stool vaccine shedding. Maternal IgA or IgG antibody titres did not have a negative impact on vaccine-like stool shedding at any timepoint. Maternal IgG (but not IgA) titres were associated with reduced take post dose 1 (p < 0.005) and 3 (p < 0.05) in the neonatal vaccine schedule group but not at study completion (week 18). In LMICs where high maternal antibodies are associated with low rotavirus vaccine efficacy, RV3-BB in a neonatal or infant vaccine schedule has the potential to provide protection against severe rotavirus disease.
高滴度的轮状病毒特异性母源抗体可能会导致中低收入国家(LMICs)的轮状病毒疫苗效力降低。RV3-BB 疫苗(G3P[6])基于新生儿轮状病毒毒株,该毒株在母乳存在的情况下能在新生儿肠道中很好地复制。本研究调查了母体血清抗体与接种 RV3-BB 疫苗的婴儿的疫苗反应之间的关系。在马拉维布兰太尔进行的 RV3-BB II 期研究中,对 561 名婴儿的母亲进行了产前血清采集,并使用酶联免疫吸附试验分析了轮状病毒特异性血清 IgA 和 IgG 抗体。婴儿接种疫苗的定义是累积 IgA 血清转换(≥3 倍增长)和/或粪便疫苗脱落。母体 IgA 或 IgG 抗体滴度对任何时间点的疫苗样粪便脱落均无负面影响。母体 IgG(而非 IgA)滴度与新生儿疫苗接种组第 1 剂后(p < 0.005)和第 3 剂后(p < 0.05)的接种量减少有关,但与研究完成时(第 18 周)的接种量减少无关。在母源抗体高而轮状病毒疫苗效力低的低收入国家,新生儿或婴儿疫苗中的 RV3-BB 有可能提供预防严重轮状病毒疾病的保护。
{"title":"Rotavirus-Specific Maternal Serum Antibodies and Vaccine Responses to RV3-BB Rotavirus Vaccine Administered in a Neonatal or Infant Schedule in Malawi.","authors":"Benjamin Morgan, Eleanor A Lyons, Amanda Handley, Nada Bogdanovic-Sakran, Daniel Pavlic, Desiree Witte, Jonathan Mandolo, Ann Turner, Khuzwayo C Jere, Frances Justice, Darren Suryawijaya Ong, Rhian Bonnici, Karen Boniface, Celeste M Donato, Ashley Mpakiza, Anell Meyer, Naor Bar-Zeev, Miren Iturriza-Gomara, Nigel A Cunliffe, Margaret Danchin, Julie E Bines","doi":"10.3390/v16091488","DOIUrl":"https://doi.org/10.3390/v16091488","url":null,"abstract":"<p><p>High titres of rotavirus-specific maternal antibodies may contribute to lower rotavirus vaccine efficacy in low- and middle-income countries (LMICs). RV3-BB vaccine (G3P[6]) is based on a neonatal rotavirus strain that replicates well in the newborn gut in the presence of breast milk. This study investigated the association between maternal serum antibodies and vaccine response in infants administered the RV3-BB vaccine. Serum was collected antenatally from mothers of 561 infants enrolled in the RV3-BB Phase II study conducted in Blantyre, Malawi, and analysed for rotavirus-specific serum IgA and IgG antibodies using enzyme-linked immunosorbent assay. Infant vaccine take was defined as cumulative IgA seroconversion (≥3 fold increase) and/or stool vaccine shedding. Maternal IgA or IgG antibody titres did not have a negative impact on vaccine-like stool shedding at any timepoint. Maternal IgG (but not IgA) titres were associated with reduced take post dose 1 (<i>p</i> < 0.005) and 3 (<i>p</i> < 0.05) in the neonatal vaccine schedule group but not at study completion (week 18). In LMICs where high maternal antibodies are associated with low rotavirus vaccine efficacy, RV3-BB in a neonatal or infant vaccine schedule has the potential to provide protection against severe rotavirus disease.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11437397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142330872","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}
Graziela Picciola Bordoni, Lucas Candido Gonçalves Barbosa, Fernando Santos Lima, Mônica de Oliveira Santos, José Daniel Gonçalves Vieira, Thais Reis Oliveira, Paulo Sérgio Scalize, Lilian Carla Carneiro
Identified as a potential reference pathogen by the WHO Guidelines for Drinking-Water Quality, Rotavirus (RV) is among the main enteric viruses that cause waterborne diseases. The aim of this study was to identify and correlate the presence of RV in collective and individual water sources of rural communities in the state of Goiás, within the seasons in which the collections were made (rainy and dry seasons). For this, 86 water samples in the dry period and 160 samples in the rainy period were collected. Concentration of water samples, extraction of viral genetic material and molecular tests were performed. When analyzing the presence of RV in the samples, taking into consideration the period studied, RV was found to be more prevalent in the dry season (54.7%) than in the rainy season (20%), showing a strong statistical association with the dry season (p-value < 0.001). The presence of pathogenic microorganisms in water is a public risk issue, enabling the emergence of outbreaks, endemics and epidemics. In the present research, there was an association between the presence of Rotavirus and the dry period of the year when compared to the rainy period.
{"title":"Short Communication: Rotavirus Group A Occurrence in Rural Water Source Samples in a Midwest Region State of Brazil, Comparing Wet and Dry Seasons.","authors":"Graziela Picciola Bordoni, Lucas Candido Gonçalves Barbosa, Fernando Santos Lima, Mônica de Oliveira Santos, José Daniel Gonçalves Vieira, Thais Reis Oliveira, Paulo Sérgio Scalize, Lilian Carla Carneiro","doi":"10.3390/v16091452","DOIUrl":"https://doi.org/10.3390/v16091452","url":null,"abstract":"<p><p>Identified as a potential reference pathogen by the WHO Guidelines for Drinking-Water Quality, Rotavirus (RV) is among the main enteric viruses that cause waterborne diseases. The aim of this study was to identify and correlate the presence of RV in collective and individual water sources of rural communities in the state of Goiás, within the seasons in which the collections were made (rainy and dry seasons). For this, 86 water samples in the dry period and 160 samples in the rainy period were collected. Concentration of water samples, extraction of viral genetic material and molecular tests were performed. When analyzing the presence of RV in the samples, taking into consideration the period studied, RV was found to be more prevalent in the dry season (54.7%) than in the rainy season (20%), showing a strong statistical association with the dry season (<i>p</i>-value < 0.001). The presence of pathogenic microorganisms in water is a public risk issue, enabling the emergence of outbreaks, endemics and epidemics. In the present research, there was an association between the presence of Rotavirus and the dry period of the year when compared to the rainy period.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11437416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142330874","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}
Taeyong Kwon, Jordan T Gebhardt, Eu Lim Lyoo, Mohammed Nooruzzaman, Natasha N Gaudreault, Igor Morozov, Diego G Diel, Juergen A Richt
The recent incursion of highly pathogenic influenza viruses into dairy cattle opens new insights for influenza virus ecology and its interspecies transmission and may have a significant impact on public health and agriculture. The aim of this study was to determine the stability of a bovine highly pathogenic avian influenza H5N1 virus isolate in the milk byproduct lactose and to evaluate two inactivation methods using industrial procedures. The bovine isolate of the highly pathogenic avian influenza H5N1 virus was stable for 14 days in a concentrated lactose solution under refrigerated conditions. Heat or citric acid treatments successfully inactivated the virus in lactose. This study highlights the persistence of HPAIV in lactose and its efficient inactivation under industrial standards.
{"title":"Bovine Highly Pathogenic Avian Influenza Virus Stability and Inactivation in the Milk Byproduct Lactose.","authors":"Taeyong Kwon, Jordan T Gebhardt, Eu Lim Lyoo, Mohammed Nooruzzaman, Natasha N Gaudreault, Igor Morozov, Diego G Diel, Juergen A Richt","doi":"10.3390/v16091451","DOIUrl":"https://doi.org/10.3390/v16091451","url":null,"abstract":"<p><p>The recent incursion of highly pathogenic influenza viruses into dairy cattle opens new insights for influenza virus ecology and its interspecies transmission and may have a significant impact on public health and agriculture. The aim of this study was to determine the stability of a bovine highly pathogenic avian influenza H5N1 virus isolate in the milk byproduct lactose and to evaluate two inactivation methods using industrial procedures. The bovine isolate of the highly pathogenic avian influenza H5N1 virus was stable for 14 days in a concentrated lactose solution under refrigerated conditions. Heat or citric acid treatments successfully inactivated the virus in lactose. This study highlights the persistence of HPAIV in lactose and its efficient inactivation under industrial standards.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11437424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142330885","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}
Objective: Coronavirus disease 2019 (COVID-19) is the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Acute respiratory distress and preterm delivery are the two major complications induced by SARS-CoV-2 infection during pregnancy. In the presence of dyspnea, the use of systemic corticosteroids was recommended in pregnant and non-pregnant groups. Our primary aim was to investigate the effect of early-onset steroid treatment on mortality and adverse effects in pregnant women with COVID-19. Our secondary aim was to investigate the effect of steroid treatment on the length of hospital stay and intensive care unit (ICU) stay, and duration of treatment. The study also investigated infection, preterm birth, and ideal body weight (lbw) in newborns.
Methods: In this retrospective study, 253 patients were divided into three groups according to steroid administration. In Group 1 patients (n:112), treatment was started at the time of hospitalization. In Group 2 patients (n:90), treatment was started at least 24 h after hospitalization. Group 3 consisted of patients (n:51) who did not receive steroid treatment. Methylprednisolone (32 mg/day) was given to pregnant patients with a gestational age below 24 weeks or above 34 weeks, and dexametazone (6 mg/day) was given in four doses followed by 32 mg/day methylprednisolone for the others (whose baby was at a gestational age of 24 weeks and above but less than 34 weeks).
Result: The hospital stay, ICU stay, and steroid administration time were significantly lower in the Group 1 when compared to the others (p < 0.05). The steroid treatment requirement was 4.4 days in Group 1 and 5.7 days in Group 2 (p < 0.05). While no death was observed in Group 1, one patient died in Group 2 and three patients died in Group 3. There was no difference between the groups in terms of complications, including preterm labor.
Conclusions: No death was also observed with early-onset treatment. Early-onset treatment may be beneficial for fewer hospitalizations, fewer ICU stays, and less mechanical ventilation requirement in pregnant women with COVID-19. In addition, with early treatment, the total number of steroid administration days was reduced, which is important in terms of reducing the risk of side effects.
{"title":"Evaluation of the Effect of Early-Onset Steroid Treatment in the COVID-19-Positive Pregnant Women on Pregnancy Outcomes.","authors":"Neval Elgormus, Abdulhalim Senyigit, Omer Okuyan, Fatma Bozkurt, Derya Sivri Aydin, Hafize Uzun","doi":"10.3390/v16091453","DOIUrl":"https://doi.org/10.3390/v16091453","url":null,"abstract":"<p><strong>Objective: </strong>Coronavirus disease 2019 (COVID-19) is the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Acute respiratory distress and preterm delivery are the two major complications induced by SARS-CoV-2 infection during pregnancy. In the presence of dyspnea, the use of systemic corticosteroids was recommended in pregnant and non-pregnant groups. Our primary aim was to investigate the effect of early-onset steroid treatment on mortality and adverse effects in pregnant women with COVID-19. Our secondary aim was to investigate the effect of steroid treatment on the length of hospital stay and intensive care unit (ICU) stay, and duration of treatment. The study also investigated infection, preterm birth, and ideal body weight (lbw) in newborns.</p><p><strong>Methods: </strong>In this retrospective study, 253 patients were divided into three groups according to steroid administration. In Group 1 patients (n:112), treatment was started at the time of hospitalization. In Group 2 patients (n:90), treatment was started at least 24 h after hospitalization. Group 3 consisted of patients (n:51) who did not receive steroid treatment. Methylprednisolone (32 mg/day) was given to pregnant patients with a gestational age below 24 weeks or above 34 weeks, and dexametazone (6 mg/day) was given in four doses followed by 32 mg/day methylprednisolone for the others (whose baby was at a gestational age of 24 weeks and above but less than 34 weeks).</p><p><strong>Result: </strong>The hospital stay, ICU stay, and steroid administration time were significantly lower in the Group 1 when compared to the others (<i>p</i> < 0.05). The steroid treatment requirement was 4.4 days in Group 1 and 5.7 days in Group 2 (<i>p</i> < 0.05). While no death was observed in Group 1, one patient died in Group 2 and three patients died in Group 3. There was no difference between the groups in terms of complications, including preterm labor.</p><p><strong>Conclusions: </strong>No death was also observed with early-onset treatment. Early-onset treatment may be beneficial for fewer hospitalizations, fewer ICU stays, and less mechanical ventilation requirement in pregnant women with COVID-19. In addition, with early treatment, the total number of steroid administration days was reduced, which is important in terms of reducing the risk of side effects.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11437463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142330931","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}
Nadine Krämer, Uxía Gestal Mato, Steffi Krauter, Nicole Büscher, Ahmad Afifi, Lina Herhaus, Luise Florin, Bodo Plachter, Christine Zimmermann
(1) Background: Intrinsic defense mechanisms are pivotal host strategies to restrict viruses already at early stages of their infection. Here, we addressed the question of how the autophagy receptor sequestome 1 (SQSTM1/p62, hereafter referred to as p62) interferes with human cytomegalovirus (HCMV) infection. (2) Methods: CRISPR/Cas9-mediated genome editing, mass spectrometry and the expression of p62 phosphovariants from recombinant HCMVs were used to address the role of p62 during infection. (3) Results: The knockout of p62 resulted in an increased release of HCMV progeny. Mass spectrometry revealed an interaction of p62 with cellular proteins required for nucleocytoplasmic transport. Phosphoproteomics further revealed that p62 is hyperphosphorylated at position S272 in HCMV-infected cells. Phosphorylated p62 showed enhanced nuclear retention, which is concordant with enhanced interaction with viral proteins relevant for genome replication and nuclear capsid egress. This modification led to reduced HCMV progeny release compared to a non-phosphorylated version of p62. (4) Conclusions: p62 is a restriction factor for HCMV replication. The activity of the receptor appears to be regulated by phosphorylation at position S272, leading to enhanced nuclear localization, viral protein degradation and impaired progeny production.
{"title":"The Autophagy Receptor <i>SQSTM1</i>/p62 Is a Restriction Factor of HCMV Infection.","authors":"Nadine Krämer, Uxía Gestal Mato, Steffi Krauter, Nicole Büscher, Ahmad Afifi, Lina Herhaus, Luise Florin, Bodo Plachter, Christine Zimmermann","doi":"10.3390/v16091440","DOIUrl":"10.3390/v16091440","url":null,"abstract":"<p><p>(1) Background: Intrinsic defense mechanisms are pivotal host strategies to restrict viruses already at early stages of their infection. Here, we addressed the question of how the autophagy receptor sequestome 1 (<i>SQSTM1</i>/p62, hereafter referred to as p62) interferes with human cytomegalovirus (HCMV) infection. (2) Methods: CRISPR/Cas9-mediated genome editing, mass spectrometry and the expression of p62 phosphovariants from recombinant HCMVs were used to address the role of p62 during infection. (3) Results: The knockout of p62 resulted in an increased release of HCMV progeny. Mass spectrometry revealed an interaction of p62 with cellular proteins required for nucleocytoplasmic transport. Phosphoproteomics further revealed that p62 is hyperphosphorylated at position S272 in HCMV-infected cells. Phosphorylated p62 showed enhanced nuclear retention, which is concordant with enhanced interaction with viral proteins relevant for genome replication and nuclear capsid egress. This modification led to reduced HCMV progeny release compared to a non-phosphorylated version of p62. (4) Conclusions: p62 is a restriction factor for HCMV replication. The activity of the receptor appears to be regulated by phosphorylation at position S272, leading to enhanced nuclear localization, viral protein degradation and impaired progeny production.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11436200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142330876","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}
Chantal J Snoeck, Aurélie Sausy, Manon Bourg, Judith M Hübschen
Since early 2024, a multistate outbreak of highly pathogenic avian influenza H5N1 has been affecting dairy cattle in the USA. The influenza viral RNA concentrations in milk make it an ideal matrix for surveillance purposes. However, viral RNA detection in multi-component fluids such as milk can be complex, and optimization of influenza detection methods is thus required. Raw bulk tank milk and mastitis milk samples were artificially contaminated with an avian influenza strain and subjected to five extraction methods. HCoV-229E and synthetic RNA were included as exogenous internal process controls. Given the high viral load usually observed in individual raw milk samples, four out of five tested methods would enable influenza detection in milk with normal texture, over a time window of at least 2 weeks post-onset of clinical signs. Nevertheless, sample dilution 1:3 in molecular transport medium prior to RNA extraction provided the best results for dilution of inhibitory substances and a good recovery rate of influenza RNA, that reached 12.5 ± 1.2% and 10.4 ± 3.8% in two independent experiments in bulk milk and 11.2 ± 3.6% and 10.0 ± 2.9% on two cohorts of mastitis milk samples. We have also shown compatibility of an influenza RT-qPCR system with synthetic RNA detection for simultaneous validation of the RNA extraction and RT-qPCR processes.
{"title":"Comparison of Extraction Methods for the Detection of Avian Influenza Virus RNA in Cattle Milk.","authors":"Chantal J Snoeck, Aurélie Sausy, Manon Bourg, Judith M Hübschen","doi":"10.3390/v16091442","DOIUrl":"https://doi.org/10.3390/v16091442","url":null,"abstract":"<p><p>Since early 2024, a multistate outbreak of highly pathogenic avian influenza H5N1 has been affecting dairy cattle in the USA. The influenza viral RNA concentrations in milk make it an ideal matrix for surveillance purposes. However, viral RNA detection in multi-component fluids such as milk can be complex, and optimization of influenza detection methods is thus required. Raw bulk tank milk and mastitis milk samples were artificially contaminated with an avian influenza strain and subjected to five extraction methods. HCoV-229E and synthetic RNA were included as exogenous internal process controls. Given the high viral load usually observed in individual raw milk samples, four out of five tested methods would enable influenza detection in milk with normal texture, over a time window of at least 2 weeks post-onset of clinical signs. Nevertheless, sample dilution 1:3 in molecular transport medium prior to RNA extraction provided the best results for dilution of inhibitory substances and a good recovery rate of influenza RNA, that reached 12.5 ± 1.2% and 10.4 ± 3.8% in two independent experiments in bulk milk and 11.2 ± 3.6% and 10.0 ± 2.9% on two cohorts of mastitis milk samples. We have also shown compatibility of an influenza RT-qPCR system with synthetic RNA detection for simultaneous validation of the RNA extraction and RT-qPCR processes.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11437502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142330906","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}
The prediction of liver-related events (LRE) after sustained virological response (SVR) in HCV-advanced chronic liver disease (ACLD) patients is crucial. We aimed to evaluate incidence and risk factors of LRE in HCV-cirrhotic patients after SVR and to assess dynamic changes of liver stiffness in participants without LRE at the end of follow-up. We enrolled 575 consecutive patients with HCV-ACLD treated with DAAs and followed up for 5 years after SVR12. Overall, 98 (17%) patients developed any type of event, and HCC was the most frequent LRE. The incidence rate was 1.6 per 100 person-years (p/y) for both HCC and hepatic decompensation. Baseline LSM ≥ 20 kPa was the only independent predictor of hepatic decompensation, while LSM ≥ 20 kPa and male sex were independent predictors of HCC development. Among the 341 participants without LRE and with paired LSM, any LSM reduction was observed in 314 (92.1%), and half of them showed a decrease of LSM ≥ 20%. Among patients without LRE, 27.3% of participants without ≥20% LSM decrease at 2 years achieved the 5-year goal; in contrast, 31.6% of participants with ≥20% LSM decrease at 2 years lost it at 5 years. These findings provide evidence that baseline LSM is a tool to stratify patients at risk of developing LRE; the dynamic changes of LSM value suggest the need for monitoring this parameter over time.
{"title":"Prediction of Clinical Trajectory in HCV-Related ACLD after SVR: Role of Liver Stiffness in a 5-Years Prospective Study.","authors":"Filomena Morisco, Alessandro Federico, Massimo Marignani, Flavia L Lombardo, Valentina Cossiga, Luisa Ranieri, Mario Romeo, Marina Cipullo, Paola Begini, Alessandra Zannella, Tommaso Stroffolini","doi":"10.3390/v16091439","DOIUrl":"https://doi.org/10.3390/v16091439","url":null,"abstract":"<p><p>The prediction of liver-related events (LRE) after sustained virological response (SVR) in HCV-advanced chronic liver disease (ACLD) patients is crucial. We aimed to evaluate incidence and risk factors of LRE in HCV-cirrhotic patients after SVR and to assess dynamic changes of liver stiffness in participants without LRE at the end of follow-up. We enrolled 575 consecutive patients with HCV-ACLD treated with DAAs and followed up for 5 years after SVR12. Overall, 98 (17%) patients developed any type of event, and HCC was the most frequent LRE. The incidence rate was 1.6 per 100 person-years (p/y) for both HCC and hepatic decompensation. Baseline LSM ≥ 20 kPa was the only independent predictor of hepatic decompensation, while LSM ≥ 20 kPa and male sex were independent predictors of HCC development. Among the 341 participants without LRE and with paired LSM, any LSM reduction was observed in 314 (92.1%), and half of them showed a decrease of LSM ≥ 20%. Among patients without LRE, 27.3% of participants without ≥20% LSM decrease at 2 years achieved the 5-year goal; in contrast, 31.6% of participants with ≥20% LSM decrease at 2 years lost it at 5 years. These findings provide evidence that baseline LSM is a tool to stratify patients at risk of developing LRE; the dynamic changes of LSM value suggest the need for monitoring this parameter over time.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11437428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142330867","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}
Mohammad A Kashem, Patrycja Sroga, Vivien Salazar, Hamza Amjad, Kate Hole, Janice Koziuk, Ming Yang, Charles Nfon, Shawn Babiuk
Foot-and-mouth disease (FMD) is one of the most infectious viral transboundary diseases of livestock, which causes devastating global economic losses. Different enzyme-linked immunosorbent assays (ELISAs) are used for sero-surveillance of the foot-and-mouth disease virus (FMDV). However, more sensitive, accurate, and convenient ELISAs are still required to detect antibodies against FMDV serotypes. The primary goal of this study was to establish serotype-specific monoclonal antibody (mAb)-based blocking ELISAs (mAb-bELISAs) that would provide better performance characteristics or be equivalent in performance characteristics compared with a conventional polyclonal antibody (pAb)-based competitive ELISA (pAb-cELISA). Four mAb-bELISAs were developed using FMDV serotype-specific mAbs for the detection of anti-FMDV/O/A/Asia1/SAT2 antibodies. Using a 50% cut-off, all four mAb-bELISAs exhibited species-independent 99.74%, 98.01%, 96.59%, and 98.55% diagnostic specificity (DSp) and 98.93%, 98.25%, 100%, and 87.50% diagnostic sensitivity (DSe) for FMDV serotypes O, A, Asia1, and SAT2, respectively. In addition, a 100% DSe of serotypes O- and SAT2-specific mAb-bELISAs was observed for porcine sera when the cut-off was 30%. All mAb-bELISAs developed in this study displayed high repeatability/reproducibility without cross-reactivity. Finally, the diagnostic performance of mAb-bELISAs was found to be better than or equivalent to compared with pAb-cELISAs, suggesting that mAb-bELISAs can be used to replace existing pAb-ELISAs for the detection of antibodies against these four FMDV serotypes.
{"title":"Development and Validation of Serotype-Specific Blocking ELISA for the Detection of Anti-FMDV O/A/Asia1/SAT2 Antibodies.","authors":"Mohammad A Kashem, Patrycja Sroga, Vivien Salazar, Hamza Amjad, Kate Hole, Janice Koziuk, Ming Yang, Charles Nfon, Shawn Babiuk","doi":"10.3390/v16091438","DOIUrl":"https://doi.org/10.3390/v16091438","url":null,"abstract":"<p><p>Foot-and-mouth disease (FMD) is one of the most infectious viral transboundary diseases of livestock, which causes devastating global economic losses. Different enzyme-linked immunosorbent assays (ELISAs) are used for sero-surveillance of the foot-and-mouth disease virus (FMDV). However, more sensitive, accurate, and convenient ELISAs are still required to detect antibodies against FMDV serotypes. The primary goal of this study was to establish serotype-specific monoclonal antibody (mAb)-based blocking ELISAs (mAb-bELISAs) that would provide better performance characteristics or be equivalent in performance characteristics compared with a conventional polyclonal antibody (pAb)-based competitive ELISA (pAb-cELISA). Four mAb-bELISAs were developed using FMDV serotype-specific mAbs for the detection of anti-FMDV/O/A/Asia1/SAT2 antibodies. Using a 50% cut-off, all four mAb-bELISAs exhibited species-independent 99.74%, 98.01%, 96.59%, and 98.55% diagnostic specificity (DSp) and 98.93%, 98.25%, 100%, and 87.50% diagnostic sensitivity (DSe) for FMDV serotypes O, A, Asia1, and SAT2, respectively. In addition, a 100% DSe of serotypes O- and SAT2-specific mAb-bELISAs was observed for porcine sera when the cut-off was 30%. All mAb-bELISAs developed in this study displayed high repeatability/reproducibility without cross-reactivity. Finally, the diagnostic performance of mAb-bELISAs was found to be better than or equivalent to compared with pAb-cELISAs, suggesting that mAb-bELISAs can be used to replace existing pAb-ELISAs for the detection of antibodies against these four FMDV serotypes.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11437413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142330912","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}
Shrews (Soricidae) are common small wild mammals. Some species of shrews, such as Asian house shrews (Suncus murinus), have a significant overlap in their habitats with humans and domestic animals. Currently, over 190 species of viruses in 32 families, including Adenoviridae, Arenaviridae, Arteriviridae, Astroviridae, Anelloviridae, Bornaviridae, Caliciviridae, Chuviridae, Coronaviridae, Filoviridae, Flaviviridae, Hantaviridae, Hepadnaviridae, Hepeviridae, Nairoviridae, Nodaviridae, Orthoherpesviridae, Orthomyxoviridae, Paramyxoviridae, Parvoviridae, Phenuiviridae, Picobirnaviridae, Picornaviridae, Polyomaviridae, Poxviridae, Rhabdoviridae, Sedoreoviridae, Spinareoviridae, and three unclassified families, have been identified in shrews. Diverse shrew viruses, such as Borna disease virus 1, Langya virus, and severe fever with thrombocytopenia syndrome virus, cause diseases in humans and/or domestic animals, posing significant threats to public health and animal health. This review compiled fundamental information about shrews and provided a comprehensive summary of the viruses that have been detected in shrews, with the aim of facilitating a deep understanding of shrews and the diversity, epidemiology, and risks of their viruses.
{"title":"Viruses Identified in Shrews (<i>Soricidae</i>) and Their Biomedical Significance.","authors":"Huan-Yu Gong, Rui-Xu Chen, Su-Mei Tan, Xiu Wang, Ji-Ming Chen, Yuan-Long Zhang, Ming Liao","doi":"10.3390/v16091441","DOIUrl":"https://doi.org/10.3390/v16091441","url":null,"abstract":"<p><p>Shrews (<i>Soricidae</i>) are common small wild mammals. Some species of shrews, such as Asian house shrews (<i>Suncus murinus</i>), have a significant overlap in their habitats with humans and domestic animals. Currently, over 190 species of viruses in 32 families, including <i>Adenoviridae</i>, <i>Arenaviridae</i>, <i>Arteriviridae</i>, <i>Astroviridae</i>, <i>Anelloviridae</i>, <i>Bornaviridae</i>, <i>Caliciviridae</i>, <i>Chuviridae</i>, <i>Coronaviridae</i>, <i>Filoviridae</i>, <i>Flaviviridae</i>, <i>Hantaviridae</i>, <i>Hepadnaviridae</i>, <i>Hepeviridae</i>, <i>Nairoviridae</i>, <i>Nodaviridae</i>, <i>Orthoherpesviridae</i>, <i>Orthomyxoviridae</i>, <i>Paramyxoviridae</i>, <i>Parvoviridae</i>, <i>Phenuiviridae</i>, <i>Picobirnaviridae</i>, <i>Picornaviridae</i>, <i>Polyomaviridae</i>, <i>Poxviridae</i>, <i>Rhabdoviridae</i>, <i>Sedoreoviridae</i>, <i>Spinareoviridae</i>, and three unclassified families, have been identified in shrews. Diverse shrew viruses, such as Borna disease virus 1, Langya virus, and severe fever with thrombocytopenia syndrome virus, cause diseases in humans and/or domestic animals, posing significant threats to public health and animal health. This review compiled fundamental information about shrews and provided a comprehensive summary of the viruses that have been detected in shrews, with the aim of facilitating a deep understanding of shrews and the diversity, epidemiology, and risks of their viruses.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11437491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142336612","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}
Julie Joseph, Thomas A Premeaux, Ritesh Tandon, Edward L Murphy, Roberta Bruhn, Christophe Nicot, Bobby Brooke Herrera, Alexander Lemenze, Reem Alatrash, Prince Baffour Tonto, Lishomwa C Ndhlovu, Pooja Jain
HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a progressive demyelinating disease of the spinal cord due to chronic inflammation. Hallmarks of disease pathology include dysfunctional anti-viral responses and the infiltration of HTLV-1-infected CD4+ T cells and HTLV-1-specific CD8+ T cells in the central nervous system. HAM/TSP individuals exhibit CD4+ and CD8+ T cells with elevated co-expression of multiple inhibitory immune checkpoint proteins (ICPs), but ICP blockade strategies can only partially restore CD8+ T-cell effector function. Exosomes, small extracellular vesicles, can enhance the spread of viral infections and blunt anti-viral responses. Here, we evaluated the impact of exosomes isolated from HTLV-1-infected cells and HAM/TSP patient sera on dendritic cell (DC) and T-cell phenotypes and function. We observed that exosomes derived from HTLV-infected cell lines (OSP2) elicit proinflammatory cytokine responses in DCs, promote helper CD4+ T-cell polarization, and suppress CD8+ T-cell effector function. Furthermore, exosomes from individuals with HAM/TSP stimulate CD4+ T-cell polarization, marked by increased Th1 and regulatory T-cell differentiation. We conclude that exosomes in the setting of HAM/TSP are detrimental to DC and T-cell function and may contribute to the progression of pathology with HTLV-1 infection.
HTLV-1相关脊髓病/热带痉挛性截瘫(HAM/TSP)是一种由慢性炎症引起的进行性脊髓脱髓鞘疾病。该病的病理特征包括抗病毒反应失调以及中枢神经系统中受 HTLV-1 感染的 CD4+ T 细胞和 HTLV-1 特异性 CD8+ T 细胞的浸润。HAM/TSP患者的CD4+和CD8+T细胞共同表达多种抑制性免疫检查点蛋白(ICP),但ICP阻断策略只能部分恢复CD8+T细胞的效应功能。外泌体是一种小的细胞外囊泡,它能增强病毒感染的传播并削弱抗病毒反应。在这里,我们评估了从HTLV-1感染细胞和HAM/TSP患者血清中分离出的外泌体对树突状细胞(DC)和T细胞表型及功能的影响。我们观察到,从HTLV感染细胞系(OSP2)中提取的外泌体可引起DC的促炎细胞因子反应,促进辅助性CD4+ T细胞极化,并抑制CD8+ T细胞的效应功能。此外,HAM/TSP 患者的外泌体可刺激 CD4+ T 细胞极化,其特征是 Th1 和调节性 T 细胞分化增加。我们的结论是,HAM/TSP患者体内的外泌体不利于直流电和T细胞功能,可能会导致HTLV-1感染的病理进展。
{"title":"Dendritic Cells Pulsed with HAM/TSP Exosomes Sensitize CD4 T Cells to Enhance HTLV-1 Infection, Induce Helper T-Cell Polarization, and Decrease Cytotoxic T-Cell Response.","authors":"Julie Joseph, Thomas A Premeaux, Ritesh Tandon, Edward L Murphy, Roberta Bruhn, Christophe Nicot, Bobby Brooke Herrera, Alexander Lemenze, Reem Alatrash, Prince Baffour Tonto, Lishomwa C Ndhlovu, Pooja Jain","doi":"10.3390/v16091443","DOIUrl":"10.3390/v16091443","url":null,"abstract":"<p><p>HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a progressive demyelinating disease of the spinal cord due to chronic inflammation. Hallmarks of disease pathology include dysfunctional anti-viral responses and the infiltration of HTLV-1-infected CD4+ T cells and HTLV-1-specific CD8+ T cells in the central nervous system. HAM/TSP individuals exhibit CD4+ and CD8+ T cells with elevated co-expression of multiple inhibitory immune checkpoint proteins (ICPs), but ICP blockade strategies can only partially restore CD8+ T-cell effector function. Exosomes, small extracellular vesicles, can enhance the spread of viral infections and blunt anti-viral responses. Here, we evaluated the impact of exosomes isolated from HTLV-1-infected cells and HAM/TSP patient sera on dendritic cell (DC) and T-cell phenotypes and function. We observed that exosomes derived from HTLV-infected cell lines (OSP2) elicit proinflammatory cytokine responses in DCs, promote helper CD4+ T-cell polarization, and suppress CD8+ T-cell effector function. Furthermore, exosomes from individuals with HAM/TSP stimulate CD4+ T-cell polarization, marked by increased Th1 and regulatory T-cell differentiation. We conclude that exosomes in the setting of HAM/TSP are detrimental to DC and T-cell function and may contribute to the progression of pathology with HTLV-1 infection.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11436225/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142330909","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}