Kazufumi Ikuta, Misako Yajima, Hiroshi Kitamura, Sorama Aoki, Teru Kanda
Placental trophoblasts constitute the interface between the fetal and maternal environments and physically prevent maternal-fetal viral transmission. However, congenital human cytomegalovirus (HCMV) infection in the early stages of pregnancy results in severe symptoms in the fetus. HCMV is the most common causative agent of intrauterine infection. To clarify the etiology of congenital HCMV infection, we focused on how the placental environment affects HCMV infection. We investigated the role of microRNAs (miRNAs), which are highly and specifically expressed in placental trophoblasts. The transfection of trophoblast-specific C19MC miRNAs, encoded by the chromosome 19 miRNA cluster, markedly enhanced HCMV Immediate Early (IE) gene expression and subsequent viral production. However, the expression of the herpes simplex virus type-1 IE gene was not changed by C19MC-BAC transfection. From among 46427 mapped genes, we identified that the expression of RAC2, a Rac family small GTPase, was markedly suppressed with an independent genetic hierarchical cluster by C19MC-BAC transfection. The suppression of RAC2 expression enhanced HCMV IE gene expression. Here, we propose the hypothesis that the placental environment contributes to HCMV-specific replication via the trophoblast-specific miRNA-mediated downregulation of RAC2 expression.
{"title":"Human Cytomegalovirus Replication Enhanced By Placental MicroRNAs.","authors":"Kazufumi Ikuta, Misako Yajima, Hiroshi Kitamura, Sorama Aoki, Teru Kanda","doi":"10.1002/jmv.70138","DOIUrl":"https://doi.org/10.1002/jmv.70138","url":null,"abstract":"<p><p>Placental trophoblasts constitute the interface between the fetal and maternal environments and physically prevent maternal-fetal viral transmission. However, congenital human cytomegalovirus (HCMV) infection in the early stages of pregnancy results in severe symptoms in the fetus. HCMV is the most common causative agent of intrauterine infection. To clarify the etiology of congenital HCMV infection, we focused on how the placental environment affects HCMV infection. We investigated the role of microRNAs (miRNAs), which are highly and specifically expressed in placental trophoblasts. The transfection of trophoblast-specific C19MC miRNAs, encoded by the chromosome 19 miRNA cluster, markedly enhanced HCMV Immediate Early (IE) gene expression and subsequent viral production. However, the expression of the herpes simplex virus type-1 IE gene was not changed by C19MC-BAC transfection. From among 46427 mapped genes, we identified that the expression of RAC2, a Rac family small GTPase, was markedly suppressed with an independent genetic hierarchical cluster by C19MC-BAC transfection. The suppression of RAC2 expression enhanced HCMV IE gene expression. Here, we propose the hypothesis that the placental environment contributes to HCMV-specific replication via the trophoblast-specific miRNA-mediated downregulation of RAC2 expression.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"96 12","pages":"e70138"},"PeriodicalIF":6.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882191","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}
Fangfang Chen, Dongmin Li, Houlin Tang, Lin Ge, Yan Cui, Peilong Li, Chang Cai, Qianqian Qin, Yichen Jin, Shuquan Qu, Zhongfu Liu, Yiming Shao, Zunyou Wu, Mengjie Han, Fan Lv
A thorough and precise comprehension understanding of the HIV epidemic is crucial for effective HIV prevention and control. This study aimed to update the estimates of the overall HIV burden in China in 2018 and to assess the trends of HIV prevalence, incidence, and mortality from 1985 to 2018. The Estimation and Projection Package (EPP)/Spectrum software was utilized for estimation, a method highly recommended by UNAIDS. Data were collected from more than 1800 HIV sentinel surveillance sites, population-based seroprevalence surveys, and HIV screening of antenatal clinics and pre-marital medical check-ups across the country. Assumptions about age and sex were used to adapt the parameters of disease progression, including CD4 progression rates and mortality rates for individuals on and off antiretroviral therapy (ART). Joinpoint (version 4.7.0.0) was used to analyze the trends of prevalence, incidence, mortality, and fatality rates from 1985 to 2018. In 2018, the total number of people living with HIV (PLWH) adults in China was estimated to be 1.23 million, corresponding to approximately 106.5/100 000 in the country. A total of 71.8% of adult PLWH were men. Over half of PLWH (58.6%) were infected through heterosexual contact, about one-third (30.2%) through male-to-male transmission, 9.0% through IDU, and 2.3% due to former plasma donation. HIV incidence in adults reached its first small peak in 1992 with 52 400 new infections (95% confidence interval: 2700-920 000). After a brief period of rapid decline between 1992 and 1994, the annual number of new infections among adults increased again and remained relatively stable at 81 000 (95% uncertainty interval [UI]: 60 000-105 000) in 2018. In recent years, the number of new infections through blood donation has been eliminated, and the number of infections through injecting drug use has been kept low. Sexual contact became the predominant transmission route, while casual sexual contact became increasingly common. Overall, HIV mortality has been steadily increasing and has recently begun to decline during the period of 2012-2018. The number of deaths from HIV/AIDS in 2018 was approximately 35 000 (95% UI: 30 000-41 000). The number of estimated PLWH in China has exceeded one million, due to the ongoing occurrence of new infections and longer survival rates. HIV transmission through blood products has been eradicated. Casual sex has become a significant mode of transmission. It is recommended to enhance the implementation of strategies and measures for sexual communication in the general population and to bolster multidisciplinary research.
{"title":"Estimates of HIV Incidence, Prevalence, and Mortality in China 2018.","authors":"Fangfang Chen, Dongmin Li, Houlin Tang, Lin Ge, Yan Cui, Peilong Li, Chang Cai, Qianqian Qin, Yichen Jin, Shuquan Qu, Zhongfu Liu, Yiming Shao, Zunyou Wu, Mengjie Han, Fan Lv","doi":"10.1002/jmv.70048","DOIUrl":"https://doi.org/10.1002/jmv.70048","url":null,"abstract":"<p><p>A thorough and precise comprehension understanding of the HIV epidemic is crucial for effective HIV prevention and control. This study aimed to update the estimates of the overall HIV burden in China in 2018 and to assess the trends of HIV prevalence, incidence, and mortality from 1985 to 2018. The Estimation and Projection Package (EPP)/Spectrum software was utilized for estimation, a method highly recommended by UNAIDS. Data were collected from more than 1800 HIV sentinel surveillance sites, population-based seroprevalence surveys, and HIV screening of antenatal clinics and pre-marital medical check-ups across the country. Assumptions about age and sex were used to adapt the parameters of disease progression, including CD4 progression rates and mortality rates for individuals on and off antiretroviral therapy (ART). Joinpoint (version 4.7.0.0) was used to analyze the trends of prevalence, incidence, mortality, and fatality rates from 1985 to 2018. In 2018, the total number of people living with HIV (PLWH) adults in China was estimated to be 1.23 million, corresponding to approximately 106.5/100 000 in the country. A total of 71.8% of adult PLWH were men. Over half of PLWH (58.6%) were infected through heterosexual contact, about one-third (30.2%) through male-to-male transmission, 9.0% through IDU, and 2.3% due to former plasma donation. HIV incidence in adults reached its first small peak in 1992 with 52 400 new infections (95% confidence interval: 2700-920 000). After a brief period of rapid decline between 1992 and 1994, the annual number of new infections among adults increased again and remained relatively stable at 81 000 (95% uncertainty interval [UI]: 60 000-105 000) in 2018. In recent years, the number of new infections through blood donation has been eliminated, and the number of infections through injecting drug use has been kept low. Sexual contact became the predominant transmission route, while casual sexual contact became increasingly common. Overall, HIV mortality has been steadily increasing and has recently begun to decline during the period of 2012-2018. The number of deaths from HIV/AIDS in 2018 was approximately 35 000 (95% UI: 30 000-41 000). The number of estimated PLWH in China has exceeded one million, due to the ongoing occurrence of new infections and longer survival rates. HIV transmission through blood products has been eradicated. Casual sex has become a significant mode of transmission. It is recommended to enhance the implementation of strategies and measures for sexual communication in the general population and to bolster multidisciplinary research.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"96 12","pages":"e70048"},"PeriodicalIF":6.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877350","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}
SARS-CoV-2 continues to mutate, leading to breakthrough infections. The development of new vaccine strategies to combat various strains is crucial. Protein cyclization can enhance thermal stability and may improve immunogenicity. Here, we designed a cyclic tandem dimeric receptor-binding domain protein (cirRBD2) via the split intein Cth-Ter. Cyclization does not affect the antigen epitopes of RBD but results in better thermal stability than that of its linear counterpart (linRBD2). Compared with the mice immunized with linRBD2, those immunized with two doses of 5 μg of cirRBD2 produced significantly greater levels of broad-spectrum neutralizing antibodies, and generated a considerable cellular immune response. In the VEEV-VRP-hACE2-transduced mouse model, two doses of 5 μg of cirRBD2 provided protection against infection with BA.5, XBB.1.9, and partial protection against EG.5 which has more mutations. This study developed a novel circular RBD dimer subunit vaccine for SARS-CoV-2 that exhibits broad-spectrum neutralizing activity against various variants. A similar strategy can be applied to develop vaccines for other pathogens, especially for thermally stable vaccines.
{"title":"A Novel Circular Delta-XBB15 RBD Dimeric Protein Subunit Vaccine Mediated by Split Intein Elicits an Immune Response and Protection Against Multiple SARS-CoV-2 Variants in Mice.","authors":"Kangyin Li, Yan Wu, Hongqing Zhang, Shaohong Chen, Bihao Wu, Tingting Li, Entao Li, Feiyang Luo, Aishun Jin, Bo Zhang, Yanan Zhang, Rui Gong, Huajun Zhang, Sandra Chiu","doi":"10.1002/jmv.70134","DOIUrl":"https://doi.org/10.1002/jmv.70134","url":null,"abstract":"<p><p>SARS-CoV-2 continues to mutate, leading to breakthrough infections. The development of new vaccine strategies to combat various strains is crucial. Protein cyclization can enhance thermal stability and may improve immunogenicity. Here, we designed a cyclic tandem dimeric receptor-binding domain protein (cirRBD2) via the split intein Cth-Ter. Cyclization does not affect the antigen epitopes of RBD but results in better thermal stability than that of its linear counterpart (linRBD2). Compared with the mice immunized with linRBD2, those immunized with two doses of 5 μg of cirRBD2 produced significantly greater levels of broad-spectrum neutralizing antibodies, and generated a considerable cellular immune response. In the VEEV-VRP-hACE2-transduced mouse model, two doses of 5 μg of cirRBD2 provided protection against infection with BA.5, XBB.1.9, and partial protection against EG.5 which has more mutations. This study developed a novel circular RBD dimer subunit vaccine for SARS-CoV-2 that exhibits broad-spectrum neutralizing activity against various variants. A similar strategy can be applied to develop vaccines for other pathogens, especially for thermally stable vaccines.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"96 12","pages":"e70134"},"PeriodicalIF":6.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877347","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}
Crimean-Congo hemorrhagic fever (CCHF) is a zoonotic infectious disease caused by the CCHF virus, a member of the Bunyavirales order and the Orthonairoviridae family. The exact pathogenesis is not fully understood. Long noncoding RNAs (lncRNAs) are RNAs that are shown to play a role in various pathological processes of viral diseases. NRAV and Lethe are two well-known lncRNAs. Although previous studies have shown that NRAV and Lethe play important roles in the pathogenesis of viral infections, their role in CCHF is unknown. This study aimed to evaluate the expression levels of NRAV and Lethe in patients with CCHFV. Eighty patients diagnosed with CCHF were included, and RNA was extracted from their blood samples. The expression of NRAV and Lethe was measured using quantitative real-time polymerase chain reaction (qPCR). Patients were divided into three groups based on severity score, which was mild, moderate, and severe, and into two groups (survivors and non-survivors). The expression levels of NRAV and Lethe were compared between these groups. Of the patients, 49 (61.25%) were male, 31 (38.75%) were female, and the mean age was 38.62 ± 19.28 years. No differences in age or gender were found between the groups. It was shown that NRAV expression was 21.86 times higher in the severe patient group compared to the moderate group and 22.74 times higher than in the mild group, statistically significant. When comparing fatal cases with survivors, NRAV expression levels were found to be 9.2 times higher in fatal cases. Lethe levels were 3 times lower in moderately severe cases compared to mild cases, but this difference was not statistically significant. In conclusion, our study suggests that NRAV may be a lncRNA involved in the pathogenesis of CCHFV.
{"title":"Investigation of Long Noncoding RNA-NRAV and Long Noncoding RNA-Lethe Expression in Crimean-Congo Hemorrhagic Fever.","authors":"Ayşenur Çömez Baysal, Yasemin Çakır Kıymaz, Nil Özbilum Şahin, Mehmet Bakır","doi":"10.1002/jmv.70142","DOIUrl":"https://doi.org/10.1002/jmv.70142","url":null,"abstract":"<p><p>Crimean-Congo hemorrhagic fever (CCHF) is a zoonotic infectious disease caused by the CCHF virus, a member of the Bunyavirales order and the Orthonairoviridae family. The exact pathogenesis is not fully understood. Long noncoding RNAs (lncRNAs) are RNAs that are shown to play a role in various pathological processes of viral diseases. NRAV and Lethe are two well-known lncRNAs. Although previous studies have shown that NRAV and Lethe play important roles in the pathogenesis of viral infections, their role in CCHF is unknown. This study aimed to evaluate the expression levels of NRAV and Lethe in patients with CCHFV. Eighty patients diagnosed with CCHF were included, and RNA was extracted from their blood samples. The expression of NRAV and Lethe was measured using quantitative real-time polymerase chain reaction (qPCR). Patients were divided into three groups based on severity score, which was mild, moderate, and severe, and into two groups (survivors and non-survivors). The expression levels of NRAV and Lethe were compared between these groups. Of the patients, 49 (61.25%) were male, 31 (38.75%) were female, and the mean age was 38.62 ± 19.28 years. No differences in age or gender were found between the groups. It was shown that NRAV expression was 21.86 times higher in the severe patient group compared to the moderate group and 22.74 times higher than in the mild group, statistically significant. When comparing fatal cases with survivors, NRAV expression levels were found to be 9.2 times higher in fatal cases. Lethe levels were 3 times lower in moderately severe cases compared to mild cases, but this difference was not statistically significant. In conclusion, our study suggests that NRAV may be a lncRNA involved in the pathogenesis of CCHFV.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"96 12","pages":"e70142"},"PeriodicalIF":6.8,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885857","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}
<p>Type 1 diabetes (T1D) is a chronic autoimmune condition that occurs when the body's immune cells destroy the insulin-producing cells (beta-cells) in the pancreas, which leads to elevated blood sugar (glucose) level or hyperglycemic condition. It is the most common form of diabetes in children, which is believed to affect more than 500, 000 children worldwide [<span>1</span>]. T1D is most common in Scandinavian and other European countries or countries with high European ancestry but is relatively rare in East Asian countries [<span>1</span>]. Diagnosis rates of T1D peak at ages 10–14 [<span>1</span>], though the presence of T1D-associated autoantibodies may result in T1D being mistaken for type 2 diabetes (T2D) in older adults or in an exacerbation of T2D development [<span>2-5</span>]. Disease development is divided into three stages, with stage 1 being characterized by the initiation of beta-cell loss, stage 2 with changes in sugar level regulation, and stage 3 with symptom onset when the disease is typically diagnosed. Treatment requires the use of administered insulin to regulate blood sugar level, but T1D condition increases the risk for long-term complications such as diabetic retinopathy, neuropathy and cardiovascular disease.</p><p>As aforementioned, most cases of T1D result from an auto-immune mediated destruction of pancreatic beta-cells that produce insulin. While the triggers for initiating this beta-cell destruction have yet to be fully understood, ample clinical and preclinical studies have associated viral infection with T1D development in genetically susceptible individuals. Several mechanisms have been proposed to explain the phenomenon of virus-induced destruction of beta-cells, such as virus-mediated interference with auto-immunity checkpoints or molecular mimicry, in which viral infection may stimulate the production of antibodies against a viral protein that may inadvertently trigger an autoimmune response against antigenically similar protein or protein components of the beta cells, which can lead to pancreatic tissue pathogenesis resulting from either the acute or chronic viral infection and tissue inflammation [<span>6, 7</span>]. Among suspected viral culprits, enteroviruses (and most prominently coxsackie B viruses) have the strongest correlational clinical data linking viral infection [<span>8-12</span>], detection of viral genomic contents [<span>13-17</span>] and seropositivity [<span>9, 16</span>] with T1D development [<span>18-20</span>]. Furthermore, animal and cell culture experiments have demonstrated cell death [<span>11, 12</span>] and the onset of auto-immune diabetes [<span>21</span>] to enteroviral infection. However, it is important to note that other studies have not found significant associations between T1D and enteroviral infection under certain circumstances [<span>7, 22, 23</span>] or that T1D development is likely to be co-dependent on additional genetic and environmental factors [<span>24</span>]
{"title":"Human Primary Macrophages Can Transmit Coxsackie B4 Virus to Pancreatic Cells In Vitro","authors":"Morgan Brisse, Hinh Ly","doi":"10.1002/jmv.70102","DOIUrl":"10.1002/jmv.70102","url":null,"abstract":"<p>Type 1 diabetes (T1D) is a chronic autoimmune condition that occurs when the body's immune cells destroy the insulin-producing cells (beta-cells) in the pancreas, which leads to elevated blood sugar (glucose) level or hyperglycemic condition. It is the most common form of diabetes in children, which is believed to affect more than 500, 000 children worldwide [<span>1</span>]. T1D is most common in Scandinavian and other European countries or countries with high European ancestry but is relatively rare in East Asian countries [<span>1</span>]. Diagnosis rates of T1D peak at ages 10–14 [<span>1</span>], though the presence of T1D-associated autoantibodies may result in T1D being mistaken for type 2 diabetes (T2D) in older adults or in an exacerbation of T2D development [<span>2-5</span>]. Disease development is divided into three stages, with stage 1 being characterized by the initiation of beta-cell loss, stage 2 with changes in sugar level regulation, and stage 3 with symptom onset when the disease is typically diagnosed. Treatment requires the use of administered insulin to regulate blood sugar level, but T1D condition increases the risk for long-term complications such as diabetic retinopathy, neuropathy and cardiovascular disease.</p><p>As aforementioned, most cases of T1D result from an auto-immune mediated destruction of pancreatic beta-cells that produce insulin. While the triggers for initiating this beta-cell destruction have yet to be fully understood, ample clinical and preclinical studies have associated viral infection with T1D development in genetically susceptible individuals. Several mechanisms have been proposed to explain the phenomenon of virus-induced destruction of beta-cells, such as virus-mediated interference with auto-immunity checkpoints or molecular mimicry, in which viral infection may stimulate the production of antibodies against a viral protein that may inadvertently trigger an autoimmune response against antigenically similar protein or protein components of the beta cells, which can lead to pancreatic tissue pathogenesis resulting from either the acute or chronic viral infection and tissue inflammation [<span>6, 7</span>]. Among suspected viral culprits, enteroviruses (and most prominently coxsackie B viruses) have the strongest correlational clinical data linking viral infection [<span>8-12</span>], detection of viral genomic contents [<span>13-17</span>] and seropositivity [<span>9, 16</span>] with T1D development [<span>18-20</span>]. Furthermore, animal and cell culture experiments have demonstrated cell death [<span>11, 12</span>] and the onset of auto-immune diabetes [<span>21</span>] to enteroviral infection. However, it is important to note that other studies have not found significant associations between T1D and enteroviral infection under certain circumstances [<span>7, 22, 23</span>] or that T1D development is likely to be co-dependent on additional genetic and environmental factors [<span>24</span>]","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"96 12","pages":""},"PeriodicalIF":6.8,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.70102","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754954","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}
Rafael Tomaz Gomes, João Simão Sobrinho, Dalva Regina Neto Pimentel, Rossana Verónica Mendoza López, Miyuki Uno, Ana Carolina Prado Ribeiro e Silva, Alan Roger Santos-Silva, Laura Sichero, Jane Tomimori
Head and neck squamous cell carcinoma (SCC) predisposing factors include smoking and alcohol consumption. However, other agents have been investigated, including viruses. We aimed to investigate the presence of DNA of four different types of human polyomavirus (HPyV) in the oral cavity and oropharyngeal SCC samples from an oncology center in Brazil and evaluate the association between HPyV detection and clinical and sociodemographic characteristics. Sixty fresh frozen samples from three different anatomical sites (tongue, floor of the mouth, and oropharynx, 20 samples for each region) were retrospectively selected. Data from medical records such as age, sex, alcohol consumption, smoking, tumor staging and death in less than 5 years of diagnosis were collected. DNA was extracted for the identification of MCPyV, BKPyV, JCPyV, and TSPyV using PCR followed by Sanger sequencing of positive samples. The identity of the generated DNA sequences was confirmed by alignment reference sequences. The investigation of the presence of HPyV DNA showed positivity of 5% for MCPyV (n = 3), 0% for both BKPyV or TSPyV, and 60% for JCPyV (n = 36). No association was found between the positivity of any HPyV in samples with any clinical or sociodemographic characteristics of the patients, nor with a certain anatomical site, except for the association between death in less than 5 years after diagnosis and positivity for JCPyV (p = 0.009). Positivity for HPyV in oral cavity and oropharyngeal SCC was low for MCPyV, high for JCPyV and null for BKPyV and TSPyV. Further studies should be carried out to better understand the high prevalence of JCPyV found in oral cavity and oropharyngeal SCC.
{"title":"Prevalence of Human Polyomaviruses in Oral and Oropharyngeal Squamous Cell Carcinoma From Patients Treated at a Cancer Center in Sao Paulo, Brazil","authors":"Rafael Tomaz Gomes, João Simão Sobrinho, Dalva Regina Neto Pimentel, Rossana Verónica Mendoza López, Miyuki Uno, Ana Carolina Prado Ribeiro e Silva, Alan Roger Santos-Silva, Laura Sichero, Jane Tomimori","doi":"10.1002/jmv.70041","DOIUrl":"https://doi.org/10.1002/jmv.70041","url":null,"abstract":"<div>\u0000 \u0000 <p>Head and neck squamous cell carcinoma (SCC) predisposing factors include smoking and alcohol consumption. However, other agents have been investigated, including viruses. We aimed to investigate the presence of DNA of four different types of human polyomavirus (HPyV) in the oral cavity and oropharyngeal SCC samples from an oncology center in Brazil and evaluate the association between HPyV detection and clinical and sociodemographic characteristics. Sixty fresh frozen samples from three different anatomical sites (tongue, floor of the mouth, and oropharynx, 20 samples for each region) were retrospectively selected. Data from medical records such as age, sex, alcohol consumption, smoking, tumor staging and death in less than 5 years of diagnosis were collected. DNA was extracted for the identification of MCPyV, BKPyV, JCPyV, and TSPyV using PCR followed by Sanger sequencing of positive samples. The identity of the generated DNA sequences was confirmed by alignment reference sequences. The investigation of the presence of HPyV DNA showed positivity of 5% for MCPyV (<i>n</i> = 3), 0% for both BKPyV or TSPyV, and 60% for JCPyV (<i>n</i> = 36). No association was found between the positivity of any HPyV in samples with any clinical or sociodemographic characteristics of the patients, nor with a certain anatomical site, except for the association between death in less than 5 years after diagnosis and positivity for JCPyV (<i>p</i> = 0.009). Positivity for HPyV in oral cavity and oropharyngeal SCC was low for MCPyV, high for JCPyV and null for BKPyV and TSPyV. Further studies should be carried out to better understand the high prevalence of JCPyV found in oral cavity and oropharyngeal SCC.</p>\u0000 </div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"96 12","pages":""},"PeriodicalIF":6.8,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749259","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}
While the SARS-CoV-2 vaccine offers 70%–95% protection effectiveness against Coronavirus disease 2019 (COVID-19), a portion of recipients do not produce adequate protective immune responses, particularly, neutralizing antibodies (nAbs). Previous studies of COVID-19 patients have identified several public antibody lineages, such as IGHV3-30, IGHV3-33, IGHV3-53, IGHV1-58, and IGHV1-24. However, it remains unclear how these public antibodies evolve during vaccination or whether there are any special antibody lineages correlated with SARS-CoV-2 vaccination. In this study, through a combination of single B cell sequencing and next-generation sequencing analysis, we systemically studied the dynamic changes of antibody lineages derived from different B cell germlines in their sequence, frequency, and neutralization ability in different vaccinees before and after receiving inactivated SARS-CoV-2 vaccines. Our findings indicate that the frequency of antibodies derived from the IGHV4-34 lineage increased in most individuals after vaccination, and the higher frequency of the antibody usually resulted in stronger binding affinity. Additionally, the ratio of IGHV4-34 derived antibodies, when compared with other public antibodies, more strongly correlated with the neutralization activity of immune sera from vaccinees. Taken together, these results suggest that IGHV4-34 is a novel vaccine-elicited public nAb lineage that plays a crucial role in immune response following inactivated COVID-19 vaccination.
{"title":"Discovery of a Novel Public Antibody Lineage Correlated With Inactivated SARS-CoV-2 Vaccine and the Resultant Neutralization Activity","authors":"Jing Wang, Shuangshuang Ni, QianQian Chen, Chenchen Wang, Hao Liu, Lina Huang, Muhammad Waqas Nasir, Wei Wang, Xiangyu Zhang, Jianjun Wu, Zhirong Liu, Jiabing Wu, Liangmin Zhang, Yong Gao","doi":"10.1002/jmv.70073","DOIUrl":"https://doi.org/10.1002/jmv.70073","url":null,"abstract":"<div>\u0000 \u0000 <p>While the SARS-CoV-2 vaccine offers 70%–95% protection effectiveness against Coronavirus disease 2019 (COVID-19), a portion of recipients do not produce adequate protective immune responses, particularly, neutralizing antibodies (nAbs). Previous studies of COVID-19 patients have identified several public antibody lineages, such as IGHV3-30, IGHV3-33, IGHV3-53, IGHV1-58, and IGHV1-24. However, it remains unclear how these public antibodies evolve during vaccination or whether there are any special antibody lineages correlated with SARS-CoV-2 vaccination. In this study, through a combination of single B cell sequencing and next-generation sequencing analysis, we systemically studied the dynamic changes of antibody lineages derived from different B cell germlines in their sequence, frequency, and neutralization ability in different vaccinees before and after receiving inactivated SARS-CoV-2 vaccines. Our findings indicate that the frequency of antibodies derived from the IGHV4-34 lineage increased in most individuals after vaccination, and the higher frequency of the antibody usually resulted in stronger binding affinity. Additionally, the ratio of IGHV4-34 derived antibodies, when compared with other public antibodies, more strongly correlated with the neutralization activity of immune sera from vaccinees. Taken together, these results suggest that IGHV4-34 is a novel vaccine-elicited public nAb lineage that plays a crucial role in immune response following inactivated COVID-19 vaccination.</p>\u0000 </div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"96 12","pages":""},"PeriodicalIF":6.8,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749301","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}
Human rotavirus A (RVA) causes acute gastroenteritis in infants and young children. The LLR RVA vaccine, which licensed in 2000 and widely used in China, significantly reduced rotavirus disease burden in China. With the changing of RV circulating strains and the emergence of new genotypes, the LLR vaccine against RVGE needed to be upgraded. In this study, we aimed to establish an RG system for the RVA vaccine strain LLR (G10P[15]). Transfection with plasmids expressing 11 genomic RNA segments of LLR along with the pCMV/868CP helper plasmid, resulted in rescue of the infectious virus with an artificially introduced genetic marker on its genome, indicating that an RG system for the LLR strain was successfully established. Furthermore, the plasmid-based reverse genetics system was used to generate lamb RVA reassortants with VP4 or VP7 genes derived from human RVA strains in China, which were not previously adapted to cell culture. We were able to rescue the six VP7 (G1, G2, G3, G4, G8, and G9) mono-reassortants, but no VP4 (P[4] or P[8]) mono-reassortant was rescued. The six VP7 reassortants covered all G-genotypes currently circulating in China and stably replicated in MA104 cells, which should be exploited as the next-generation rotavirus vaccines candidates in China. Furthermore, the LLR RG system in this study will be a useful vaccine vector for intestinal pathogens such as norovirus and Vibrio cholerae.
{"title":"Establishment of a Reverse Genetics System for Rotavirus Vaccine Strain LLR and Developing Vaccine Candidates Carrying VP7 Gene Cloned From Human Strains Circulating in China","authors":"Xiafei Liu, Shan Li, Junjie Yu, Pengdi Chai, Zhiping Xie, Lili Pang, Jinsong Li, Wuyang Zhu, Weihong Ren, Zhaojun Duan","doi":"10.1002/jmv.70065","DOIUrl":"https://doi.org/10.1002/jmv.70065","url":null,"abstract":"<div>\u0000 \u0000 <p>Human rotavirus A (RVA) causes acute gastroenteritis in infants and young children. The LLR RVA vaccine, which licensed in 2000 and widely used in China, significantly reduced rotavirus disease burden in China. With the changing of RV circulating strains and the emergence of new genotypes, the LLR vaccine against RVGE needed to be upgraded. In this study, we aimed to establish an RG system for the RVA vaccine strain LLR (G10P[15]). Transfection with plasmids expressing 11 genomic RNA segments of LLR along with the pCMV/868CP helper plasmid, resulted in rescue of the infectious virus with an artificially introduced genetic marker on its genome, indicating that an RG system for the LLR strain was successfully established. Furthermore, the plasmid-based reverse genetics system was used to generate lamb RVA reassortants with VP4 or VP7 genes derived from human RVA strains in China, which were not previously adapted to cell culture. We were able to rescue the six VP7 (G1, G2, G3, G4, G8, and G9) mono-reassortants, but no VP4 (P[4] or P[8]) mono-reassortant was rescued. The six VP7 reassortants covered all G-genotypes currently circulating in China and stably replicated in MA104 cells, which should be exploited as the next-generation rotavirus vaccines candidates in China. Furthermore, the LLR RG system in this study will be a useful vaccine vector for intestinal pathogens such as norovirus and Vibrio cholerae.</p></div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"96 12","pages":""},"PeriodicalIF":6.8,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749233","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}
Marija Suka, Valentina Cirkovic, Marina Siljic, Marko Jankovic, Ana Loncar, Milica Rajkovic, Gorana Stamenkovic, Olivera Vukicevic-Radic, Maja Stanojevic
West Nile Virus (WNV) is considered one of the most widely distributed arboviruses worldwide. In 2018, Serbia was among the European countries reporting the highest number of WNV cases. This study aimed to characterize WNV strains circulating in Serbia, and to estimate the pathways and dynamics of WNV-2 spread in the Balkans and globally through the phylogenetic approach. Fifty newly generated NS5 Serbian sequences were found to belong to WNV lineage 2. Phylodynamic analyses of the Balkan clade indicated the potential for an increase in genetic diversity and structure of virus populations. Presented phylogeographic analyses implied four instances of long-distance WNV-2 migration from Africa to Europe, during the 1940s to 1950s, while further dissemination of WNV-2 originated in Hungary in mid-1970s and subsequently spread to Austria and Serbia. Extensive dispersion took place during the 1990s–2000s, as the virus spread from Austria to central and western Europe, and from Hungary to the Balkans. Continuous phylogeography analysis of the Balkans WNV-2 clade implied the central role of Serbia for WNV dissemination across the Balkan peninsula. Furthermore, previously undocumented instance of intercontinental migration of WNV-2 from Europe to Asia was implied. In-depth phylogenetic investigation into the global distribution of WNV-2 may provide valuable insights into the prediction and prevention of potential epidemics.
{"title":"Dynamics of West Nile Virus Lineage 2 Spread in the Balkans in the Context of Global Spatio-Temporal Dispersal","authors":"Marija Suka, Valentina Cirkovic, Marina Siljic, Marko Jankovic, Ana Loncar, Milica Rajkovic, Gorana Stamenkovic, Olivera Vukicevic-Radic, Maja Stanojevic","doi":"10.1002/jmv.70092","DOIUrl":"https://doi.org/10.1002/jmv.70092","url":null,"abstract":"<div>\u0000 \u0000 <p>West Nile Virus (WNV) is considered one of the most widely distributed arboviruses worldwide. In 2018, Serbia was among the European countries reporting the highest number of WNV cases. This study aimed to characterize WNV strains circulating in Serbia, and to estimate the pathways and dynamics of WNV-2 spread in the Balkans and globally through the phylogenetic approach. Fifty newly generated NS5 Serbian sequences were found to belong to WNV lineage 2. Phylodynamic analyses of the Balkan clade indicated the potential for an increase in genetic diversity and structure of virus populations. Presented phylogeographic analyses implied four instances of long-distance WNV-2 migration from Africa to Europe, during the 1940s to 1950s, while further dissemination of WNV-2 originated in Hungary in mid-1970s and subsequently spread to Austria and Serbia. Extensive dispersion took place during the 1990s–2000s, as the virus spread from Austria to central and western Europe, and from Hungary to the Balkans. Continuous phylogeography analysis of the Balkans WNV-2 clade implied the central role of Serbia for WNV dissemination across the Balkan peninsula. Furthermore, previously undocumented instance of intercontinental migration of WNV-2 from Europe to Asia was implied. In-depth phylogenetic investigation into the global distribution of WNV-2 may provide valuable insights into the prediction and prevention of potential epidemics.</p></div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"96 12","pages":""},"PeriodicalIF":6.8,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749234","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}
Marianne Graninger, Verena Endmayr, Laura M. Kühner, Sarah M. Berger, Paulus Rommer, Sigrid Klotz, Ellen Gelpi, Hannes Vietzen, Romana Höftberger, Elisabeth Puchhammer-Stöckl
Long coronavirus disease 2019 (COVID) (LC) symptoms including pain and autonomic dysfunction are in some patients associated with small-fiber neuropathy (SFN). The pathomechanisms underlying SFN are mostly unclear. Natural killer (NK) cells play a crucial role in immune regulation, viral clearance and nerve metabolism. The aim of this study was to identify associations between development of small-fiber dysfunction dependent and independent of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and human genetic markers associated with specific NK cell functions. The genetic markers assessed in all cohorts included: FCGR3A, IGHG1, HLA-E, NKG2C, and rs9916629. Genotyping was performed using TaqMan assays, Sanger sequencing and touchdown polymerase chain reaction. We assessed human cytomegalovirus (HCMV) IgG serostatus in all participants, and screened for anti-neuronal, anti-glial and anti-ganglioside autoantibodies in both patient cohorts. We included 50 LC patients with newly-emerged symptoms of small-fiber dysfunction after SARS-CoV-2 infection, 27 prepandemic SFN patients and 320 control persons. Markers associated with low NKG2C response, that is, deletion of the NKG2C gene and lack of prior HCMV infection (IgG seronegativity), occurred significantly more frequently in prepandemic SFN patients compared to LC patients and controls (p = 0.0109 and 0.0005, respectively). In conclusion, markers of impaired NKG2C pathways are associated with prepandemic SFN, but not with Long COVID-associated small-fiber dysfunction.
{"title":"Association Between NK Cell Genetic Variants and the Development of Long COVID Associated- and Prepandemic Small Fiber Neuropathy","authors":"Marianne Graninger, Verena Endmayr, Laura M. Kühner, Sarah M. Berger, Paulus Rommer, Sigrid Klotz, Ellen Gelpi, Hannes Vietzen, Romana Höftberger, Elisabeth Puchhammer-Stöckl","doi":"10.1002/jmv.70091","DOIUrl":"https://doi.org/10.1002/jmv.70091","url":null,"abstract":"<p>Long coronavirus disease 2019 (COVID) (LC) symptoms including pain and autonomic dysfunction are in some patients associated with small-fiber neuropathy (SFN). The pathomechanisms underlying SFN are mostly unclear. Natural killer (NK) cells play a crucial role in immune regulation, viral clearance and nerve metabolism. The aim of this study was to identify associations between development of small-fiber dysfunction dependent and independent of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and human genetic markers associated with specific NK cell functions. The genetic markers assessed in all cohorts included: <i>FCGR3A</i>, <i>IGHG1</i>, <i>HLA-E</i>, <i>NKG2C</i>, and rs9916629. Genotyping was performed using TaqMan assays, Sanger sequencing and touchdown polymerase chain reaction. We assessed human cytomegalovirus (HCMV) IgG serostatus in all participants, and screened for anti-neuronal, anti-glial and anti-ganglioside autoantibodies in both patient cohorts. We included 50 LC patients with newly-emerged symptoms of small-fiber dysfunction after SARS-CoV-2 infection, 27 prepandemic SFN patients and 320 control persons. Markers associated with low NKG2C response, that is, deletion of the <i>NKG2C</i> gene and lack of prior HCMV infection (IgG seronegativity), occurred significantly more frequently in prepandemic SFN patients compared to LC patients and controls (<i>p</i> = 0.0109 and 0.0005, respectively). In conclusion, markers of impaired NKG2C pathways are associated with prepandemic SFN, but not with Long COVID-associated small-fiber dysfunction.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"96 12","pages":""},"PeriodicalIF":6.8,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.70091","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749235","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号