Jana Zeitvogel, Katinka Döhner, Ilona Klug, Timmy Richardo, Beate Sodeik, Thomas Werfel
Eczema herpeticum (EH) is a disseminated severe herpes simplex virus type 1 (HSV-1) infection that mainly occurs in a subset of patients suffering from atopic dermatitis (AD). EH is complex and multifaceted, involving immunological changes, environmental influences, and genetic aberrations. Certain genetic variants of the thymic stromal lymphopoietin (TSLP) may predispose to develop severe HSV-1-induced eczema. Therefore, we investigated the impact of TSLP on HSV-1 infection. TSLP encodes for two distinct forms: a long-form (lfTSLP), primarily associated with type 2 immunity, and a short-form (sfTSLP) with anti-inflammatory and antimicrobial properties. While sfTSLP reduced HSV-1 infectibility in human primary keratinocytes (HPK), lfTSLP did not. In HPK treated with sfTSLP, HSV-1 gene expression, and replication decreased, while virion binding to cells and targeting of incoming capsids to the nucleus were not diminished compared to untreated cells. sfTSLP caused only minor changes in the expression of innate immunity cytokines, and its inhibition of HSV-1 infection did not require de novo protein synthesis. Time window experiments indicated a different antiviral mechanism than LL-37. sfTSLP showed the strongest antiviral effect when administered to HPK before or after inoculation with HSV-1, and outperformed the inhibitory potential of LL-37 under these conditions. Our data show that sfTSLP has antiviral functions and promotes repression of the HSV-1 infection in HPK.
{"title":"Short-form thymic stromal lymphopoietin (sfTSLP) restricts herpes simplex virus infection of human primary keratinocytes","authors":"Jana Zeitvogel, Katinka Döhner, Ilona Klug, Timmy Richardo, Beate Sodeik, Thomas Werfel","doi":"10.1002/jmv.29865","DOIUrl":"10.1002/jmv.29865","url":null,"abstract":"<p>Eczema herpeticum (EH) is a disseminated severe herpes simplex virus type 1 (HSV-1) infection that mainly occurs in a subset of patients suffering from atopic dermatitis (AD). EH is complex and multifaceted, involving immunological changes, environmental influences, and genetic aberrations. Certain genetic variants of the thymic stromal lymphopoietin (<i>TSLP</i>) may predispose to develop severe HSV-1-induced eczema. Therefore, we investigated the impact of TSLP on HSV-1 infection. <i>TSLP</i> encodes for two distinct forms: a long-form (lfTSLP), primarily associated with type 2 immunity, and a short-form (sfTSLP) with anti-inflammatory and antimicrobial properties. While sfTSLP reduced HSV-1 infectibility in human primary keratinocytes (HPK), lfTSLP did not. In HPK treated with sfTSLP, HSV-1 gene expression, and replication decreased, while virion binding to cells and targeting of incoming capsids to the nucleus were not diminished compared to untreated cells. sfTSLP caused only minor changes in the expression of innate immunity cytokines, and its inhibition of HSV-1 infection did not require <i>de novo</i> protein synthesis. Time window experiments indicated a different antiviral mechanism than LL-37. sfTSLP showed the strongest antiviral effect when administered to HPK before or after inoculation with HSV-1, and outperformed the inhibitory potential of LL-37 under these conditions. Our data show that sfTSLP has antiviral functions and promotes repression of the HSV-1 infection in HPK.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.29865","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132921","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}
Van Thi Lo, Hyun A. Lim, Seong Sik Jang, Min Chan Kim, Alain Chrysler Chamfort, Ha Yeon Kim, Da Young Mun, Min Chang Kang, Han Byul Lee, Sunjoo Kim, Younghee Lee, Sangkyu Park, Sun-Woo Yoon, Hye Kwon Kim
The N121 site on the spike protein of SARS-CoV-2 is associated with heme and its metabolite, biliverdin, which can affect antibody binding. Both N121T and N121S substitutions have been observed in natural conditions and in a hamster model of dual infection with SARS-CoV-2 and Influenza A virus. Serum pseudotype neutralization assays against HIV-1 particles carrying wild-type, N121T, and N121S spikes with immune mouse and human sera revealed that N121T and N121S mutations had a greater impact on serum neutralization than biliverdin treatment. Although N121T and N121S substitutions are not currently major SARS-CoV-2 variants of concern, this study could provide fundamental information to prepare for potential future mutations at the N121 site of SARS-CoV-2.
{"title":"N121T and N121S substitutions on the SARS-CoV-2 spike protein impact on serum neutralization","authors":"Van Thi Lo, Hyun A. Lim, Seong Sik Jang, Min Chan Kim, Alain Chrysler Chamfort, Ha Yeon Kim, Da Young Mun, Min Chang Kang, Han Byul Lee, Sunjoo Kim, Younghee Lee, Sangkyu Park, Sun-Woo Yoon, Hye Kwon Kim","doi":"10.1002/jmv.29871","DOIUrl":"10.1002/jmv.29871","url":null,"abstract":"<p>The N121 site on the spike protein of SARS-CoV-2 is associated with heme and its metabolite, biliverdin, which can affect antibody binding. Both N121T and N121S substitutions have been observed in natural conditions and in a hamster model of dual infection with SARS-CoV-2 and Influenza A virus. Serum pseudotype neutralization assays against HIV-1 particles carrying wild-type, N121T, and N121S spikes with immune mouse and human sera revealed that N121T and N121S mutations had a greater impact on serum neutralization than biliverdin treatment. Although N121T and N121S substitutions are not currently major SARS-CoV-2 variants of concern, this study could provide fundamental information to prepare for potential future mutations at the N121 site of SARS-CoV-2.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108166","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>Blood coagulation relies on a cascade of protein-protein interactions that comprise two primary downstream pathways (intrinsic and extrinsic<span><sup>1</sup></span>). Individuals deficient in certain coagulation pathway proteins, also known as clotting factors, may present with primary or secondary bleeding disorders (coagulopathies). For example, hemophilia results from genetic alterations to factors VIII, IX or XI,<span><sup>2</sup></span> while secondary bleeding disorders may result from dysregulation of clotting factors caused by underlying conditions,<span><sup>3-5</sup></span> medication use,<span><sup>6</sup></span> or infection.<span><sup>7-9</sup></span> Concentrated coagulation factors derived from human blood donations have been made available for treating bleeding disorders since the 1970s.<span><sup>10, 11</sup></span> However, therapeutic coagulation-factor use was found in the 1980s to be associated with a significantly increased risk of developing disease from the then newly discovered blood-borne pathogens (BBPs), such as human immunodeficiency virus-1 (HIV-1, discovered in 1983) and hepatitis C virus (HCV, discovered in 1990).<span><sup>12-15</sup></span> Measures were subsequently put into place throughout the mid-to-late 1980s and early 1990s to limit BBP spread to patients, who were using clotting factor products. Those practices included viral detection, viral exclusion and inactivation, and blood donor screening.</p><p>The degree of viral burden carried by clotting factor products before viral exclusion practices remained unknown with regard to contamination with HCV, HIV-1 and/or other BBPs that had since been found in patients with hemophilia (PWHs).<span><sup>16-19</sup></span> The authors of a newly published article in the Journal of Medical Virology<span><sup>20</sup></span> retrospectively identified BBPs present in 24 lyophilized clotting factor samples (14 commercially produced clothing factors and 10 from non-remunerated blood donors) taken from three time periods: 1974–1977, 1981–1985 and 1989–1992. Blood factor products (either single coagulation factor or a combination of the factors) came from commercial and nationalized (British and French blood bank) sources and were sorted by their listed expiration dates (Figure 1), as production date for each of them was not recorded. Using established or in-house developed qPCR assays, the authors intended to test those products for HIV-1, HIV-2, hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis E virus (HEV), human pegiviruses 1 and 2 (HPgV1, HPgV2), and the parvoviruses B19V and PARV4. It is important to note that while the authors stated in the abstract that HIV-2 would be part of a panel of BBPs to be tested, they did not report the result of this test in the subsequent sections of the manuscript. It is, therefore, unclear whether this had been done for this study. Regardless, samples identified as positive for HCV or HIV-1
{"title":"Retroactive blood-borne pathogens detection of archival clotting factor concentrates throughout the 1970s and 1980s highlights virus contaminations","authors":"Morgan Brisse, Hinh Ly","doi":"10.1002/jmv.29907","DOIUrl":"10.1002/jmv.29907","url":null,"abstract":"<p>Blood coagulation relies on a cascade of protein-protein interactions that comprise two primary downstream pathways (intrinsic and extrinsic<span><sup>1</sup></span>). Individuals deficient in certain coagulation pathway proteins, also known as clotting factors, may present with primary or secondary bleeding disorders (coagulopathies). For example, hemophilia results from genetic alterations to factors VIII, IX or XI,<span><sup>2</sup></span> while secondary bleeding disorders may result from dysregulation of clotting factors caused by underlying conditions,<span><sup>3-5</sup></span> medication use,<span><sup>6</sup></span> or infection.<span><sup>7-9</sup></span> Concentrated coagulation factors derived from human blood donations have been made available for treating bleeding disorders since the 1970s.<span><sup>10, 11</sup></span> However, therapeutic coagulation-factor use was found in the 1980s to be associated with a significantly increased risk of developing disease from the then newly discovered blood-borne pathogens (BBPs), such as human immunodeficiency virus-1 (HIV-1, discovered in 1983) and hepatitis C virus (HCV, discovered in 1990).<span><sup>12-15</sup></span> Measures were subsequently put into place throughout the mid-to-late 1980s and early 1990s to limit BBP spread to patients, who were using clotting factor products. Those practices included viral detection, viral exclusion and inactivation, and blood donor screening.</p><p>The degree of viral burden carried by clotting factor products before viral exclusion practices remained unknown with regard to contamination with HCV, HIV-1 and/or other BBPs that had since been found in patients with hemophilia (PWHs).<span><sup>16-19</sup></span> The authors of a newly published article in the Journal of Medical Virology<span><sup>20</sup></span> retrospectively identified BBPs present in 24 lyophilized clotting factor samples (14 commercially produced clothing factors and 10 from non-remunerated blood donors) taken from three time periods: 1974–1977, 1981–1985 and 1989–1992. Blood factor products (either single coagulation factor or a combination of the factors) came from commercial and nationalized (British and French blood bank) sources and were sorted by their listed expiration dates (Figure 1), as production date for each of them was not recorded. Using established or in-house developed qPCR assays, the authors intended to test those products for HIV-1, HIV-2, hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis E virus (HEV), human pegiviruses 1 and 2 (HPgV1, HPgV2), and the parvoviruses B19V and PARV4. It is important to note that while the authors stated in the abstract that HIV-2 would be part of a panel of BBPs to be tested, they did not report the result of this test in the subsequent sections of the manuscript. It is, therefore, unclear whether this had been done for this study. Regardless, samples identified as positive for HCV or HIV-1","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.29907","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120004","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 active form of vitamin D (VD) exerts hormonal effects by regulating the expression of genes involved in T-cell activity, cell differentiation, and proliferation. Human T-cell leukemia virus type 1 (HTLV-1) is a causative agent of life-threatening diseases, adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy (HAM). Among ATL patients, hypercalcemia is one of the most serious complications due to bone resorption. In this study, wild-type mice administered UV-irradiated HTLV-1-infected cells showed up to 47% decrease of plasma VD level compared with untreated mice. To clarify the effect of HTLV-1 on plasma VD level, 315 samples registered in nationwide cohort study on ATL onset were measured. The VD level in HAM (14.98 ± 8.5 ng/mL) was significantly lower than those in asymptomatic carriers and ATL (p < 0.05). Upon comparing the VD levels in ATL stratified by disease subtypes, acute ATL showed a lower level (15.81 ± 12.0 ng/mL) than chronic and smoldering types (p < 0.05). In the longitudinal observation, VD levels were significantly higher in untreated spontaneous remission cases than in ATL progression cases, in which the VD levels decreased approximately 40% after onset. In cases of relapse after transplantation, the plasma VD level dropped to 38.7% of the pre-relapse level, while in cases of complete remission, the VD level increased with improvement of the performance status. Taken together, these results suggest that plasma VD level is a potential indicator for the onset and relapse of HTLV-1-associated diseases.
维生素 D (VD) 的活性形式通过调节参与 T 细胞活性、细胞分化和增殖的基因的表达来发挥激素作用。人类 T 细胞白血病病毒 1 型(HTLV-1)是威胁生命的疾病--成人 T 细胞白血病(ATL)和 HTLV-1 相关骨髓病(HAM)的致病因子。在 ATL 患者中,高钙血症是骨吸收导致的最严重并发症之一。在这项研究中,给野生型小鼠注射经紫外线照射的 HTLV-1 感染细胞后,其血浆 VD 水平比未经处理的小鼠下降了 47%。为了明确 HTLV-1 对血浆 VD 水平的影响,我们对全国范围内有关 ATL 发病的队列研究中登记的 315 个样本进行了测量。HAM的VD水平(14.98 ± 8.5 ng/mL)明显低于无症状携带者和ATL(p
{"title":"Plasma vitamin D levels are correlated with the pathogenesis of human T-cell leukemia virus type 1-associated diseases","authors":"Yasuko Sagara, Hitomi Nakamura, Yasuhiro Sagara, Etsuko Shitsuta, Kaoru Uchimaru, Yoshihisa Yamano, Toshiki Watanabe, Kiyonori Miura, Koji Matsuzaki","doi":"10.1002/jmv.29898","DOIUrl":"10.1002/jmv.29898","url":null,"abstract":"<p>The active form of vitamin D (VD) exerts hormonal effects by regulating the expression of genes involved in T-cell activity, cell differentiation, and proliferation. Human T-cell leukemia virus type 1 (HTLV-1) is a causative agent of life-threatening diseases, adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy (HAM). Among ATL patients, hypercalcemia is one of the most serious complications due to bone resorption. In this study, wild-type mice administered UV-irradiated HTLV-1-infected cells showed up to 47% decrease of plasma VD level compared with untreated mice. To clarify the effect of HTLV-1 on plasma VD level, 315 samples registered in nationwide cohort study on ATL onset were measured. The VD level in HAM (14.98 ± 8.5 ng/mL) was significantly lower than those in asymptomatic carriers and ATL (<i>p</i> < 0.05). Upon comparing the VD levels in ATL stratified by disease subtypes, acute ATL showed a lower level (15.81 ± 12.0 ng/mL) than chronic and smoldering types (<i>p</i> < 0.05). In the longitudinal observation, VD levels were significantly higher in untreated spontaneous remission cases than in ATL progression cases, in which the VD levels decreased approximately 40% after onset. In cases of relapse after transplantation, the plasma VD level dropped to 38.7% of the pre-relapse level, while in cases of complete remission, the VD level increased with improvement of the performance status. Taken together, these results suggest that plasma VD level is a potential indicator for the onset and relapse of HTLV-1-associated diseases.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108175","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}
Marc Arbyn, Kate Cuschieri, Jesper Bonde, Rob Schuurman, Clementina Cocuzza, Davy Vanden Broeck, Fang-Hui Zhao, Remila Rezhake, Murat Gultekin, Silvia de Sanjosé, Karen Canfell, David Hawkes, Marion Saville, Peter Hillemanns, Joakim Dillner, Johannes Berkhof, Jean-Luc Prétet, Tarik Gheit, Gary Clifford, Partha Basu, Maribel Almonte, Nicolas Wentzensen, Mario Poljak
While HC2 and GP5+/6+ PCR-EIA were pivotal in test validation of new HPV assays, they represent the first generation of comparator tests based upon technologies that are not in widespread use anymore. In the current guideline, criteria for second-generation comparator tests are presented that include more detailed resolution of HPV genotypes. Second-generation comparator tests should preferentially target only the 12 genotypes classified as carcinogenic (IARC-group I), and show consistent non-inferior sensitivity for CIN2+ and CIN3+ and specificity for ≤CIN1 compared to one of the first-generations comparators, in at least three validation studies using benchmarks of 0.95 for relative sensitivity and 0.98 for relative specificity. Validation should take into account used storage media and other sample handling procedures. Meta-analyses were conducted to identify the assays that fulfill these stringent criteria. Four tests fulfilled the new criteria: (1) RealTime High-Risk HPV Test (Abbott), (2) Cobas-4800 HPV test (Roche Molecular System), (3) Onclarity HPV Assay (BD Diagnostics), and (4) Anyplex II HPV HR Detection (Seegene), each evaluated in three to six studies. Whereas the four assays target 14 carcinogenic genotypes, the first two identify separately HPV16 and 18, the third assay identifies five types separately and the fourth identifies all the types separately.
{"title":"Criteria for second generation comparator tests in validation of novel HPV DNA tests for use in cervical cancer screening","authors":"Marc Arbyn, Kate Cuschieri, Jesper Bonde, Rob Schuurman, Clementina Cocuzza, Davy Vanden Broeck, Fang-Hui Zhao, Remila Rezhake, Murat Gultekin, Silvia de Sanjosé, Karen Canfell, David Hawkes, Marion Saville, Peter Hillemanns, Joakim Dillner, Johannes Berkhof, Jean-Luc Prétet, Tarik Gheit, Gary Clifford, Partha Basu, Maribel Almonte, Nicolas Wentzensen, Mario Poljak","doi":"10.1002/jmv.29881","DOIUrl":"10.1002/jmv.29881","url":null,"abstract":"<p>While HC2 and GP5+/6+ PCR-EIA were pivotal in test validation of new HPV assays, they represent the first generation of comparator tests based upon technologies that are not in widespread use anymore. In the current guideline, criteria for second-generation comparator tests are presented that include more detailed resolution of HPV genotypes. Second-generation comparator tests should preferentially target only the 12 genotypes classified as carcinogenic (IARC-group I), and show consistent non-inferior sensitivity for CIN2+ and CIN3+ and specificity for ≤CIN1 compared to one of the first-generations comparators, in at least three validation studies using benchmarks of 0.95 for relative sensitivity and 0.98 for relative specificity. Validation should take into account used storage media and other sample handling procedures. Meta-analyses were conducted to identify the assays that fulfill these stringent criteria. Four tests fulfilled the new criteria: (1) RealTime High-Risk HPV Test (Abbott), (2) Cobas-4800 HPV test (Roche Molecular System), (3) Onclarity HPV Assay (BD Diagnostics), and (4) Anyplex II HPV HR Detection (Seegene), each evaluated in three to six studies. Whereas the four assays target 14 carcinogenic genotypes, the first two identify separately HPV16 and 18, the third assay identifies five types separately and the fourth identifies all the types separately.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.29881","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Epidemiological and clinical overview of the 2024 Oropouche virus disease outbreaks, an emerging/re-emerging neurotropic arboviral disease and global public health threat","authors":"Benjamin M. Liu","doi":"10.1002/jmv.29897","DOIUrl":"10.1002/jmv.29897","url":null,"abstract":"","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108165","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}
Nabila Tabassum, Kaljit Bhuller, Amy Webster, Farah Siddiqui, Suzanna Dunkerton, Manjiri Khare, Breslin Eamonn, Hatem A. Mousa, Ian Scudamore, Damian Roland, Rachel Rowlands, Srini Bandi, Vinayak R. Rai, Atul Bagul, Jorge Jesus-Silva, Paul W. Bird, Sarah R. Young, Lucy James, Oliver T. R. Toovey, Julian W. Tang
{"title":"Clinical impact of recent surge in acute parvovirus B19 infections in Leicester UK, March–July 2024","authors":"Nabila Tabassum, Kaljit Bhuller, Amy Webster, Farah Siddiqui, Suzanna Dunkerton, Manjiri Khare, Breslin Eamonn, Hatem A. Mousa, Ian Scudamore, Damian Roland, Rachel Rowlands, Srini Bandi, Vinayak R. Rai, Atul Bagul, Jorge Jesus-Silva, Paul W. Bird, Sarah R. Young, Lucy James, Oliver T. R. Toovey, Julian W. Tang","doi":"10.1002/jmv.29903","DOIUrl":"10.1002/jmv.29903","url":null,"abstract":"","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120002","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}
The ubiquitin-proteasome system is frequently employed to degrade viral proteins, thereby inhibiting viral replication and pathogenicity. Through an analysis of the degradation kinetics of all the SARS-CoV-2 proteins, our study revealed rapid degradation of several proteins, particularly NSP5. Additionally, we identified FBXO22, an E3 ubiquitin ligase, as the primary regulator of NSP5 ubiquitination. Moreover, we validated the interaction between FBXO22 and NSP5, demonstrating that FBXO22-mediated ubiquitination of NSP5 facilitated its recognition by the proteasome, leading to subsequent degradation. Specifically, FBXO22 catalyzed the formation of K48-linked polyubiquitin chains on NSP5 at lysine residues 5 and 90. Knockdown of FBXO22 resulted in decreased NSP5 ubiquitination levels, increased stability, and enhanced ability to evade the host innate immune response. Notably, the protein level of FBXO22 were negatively correlated with SARS-CoV-2 load, highlighting its importance in inhibiting viral replication. This study elucidates the molecular mechanism by which FBXO22 mediates the degradation of NSP5 and underscores its critical role in limiting viral replication. The identification of FBXO22 as a regulator of NSP5 stability provides new insights and potential avenues for targeting NSP5 in antiviral strategies.
{"title":"E3 ubiquitin ligase FBXO22 inhibits SARS-CoV-2 replication via promoting proteasome-dependent degradation of NSP5","authors":"Yuzheng Zhou, Wei Feng, Chuwei Yang, Xiafei Wei, Lujie Fan, Yezi Wu, Xiang Gao, Xiaotong Shen, Zheng Zhang, Juanjuan Zhao","doi":"10.1002/jmv.29891","DOIUrl":"10.1002/jmv.29891","url":null,"abstract":"<p>The ubiquitin-proteasome system is frequently employed to degrade viral proteins, thereby inhibiting viral replication and pathogenicity. Through an analysis of the degradation kinetics of all the SARS-CoV-2 proteins, our study revealed rapid degradation of several proteins, particularly NSP5. Additionally, we identified FBXO22, an E3 ubiquitin ligase, as the primary regulator of NSP5 ubiquitination. Moreover, we validated the interaction between FBXO22 and NSP5, demonstrating that FBXO22-mediated ubiquitination of NSP5 facilitated its recognition by the proteasome, leading to subsequent degradation. Specifically, FBXO22 catalyzed the formation of K48-linked polyubiquitin chains on NSP5 at lysine residues 5 and 90. Knockdown of FBXO22 resulted in decreased NSP5 ubiquitination levels, increased stability, and enhanced ability to evade the host innate immune response. Notably, the protein level of FBXO22 were negatively correlated with SARS-CoV-2 load, highlighting its importance in inhibiting viral replication. This study elucidates the molecular mechanism by which FBXO22 mediates the degradation of NSP5 and underscores its critical role in limiting viral replication. The identification of FBXO22 as a regulator of NSP5 stability provides new insights and potential avenues for targeting NSP5 in antiviral strategies.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120003","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}
The natural history of cervical cancer is closely linked to that of high-risk human papillomaviruses (HPV) infection. It is recognized that upon HPV DNA integration, partial or complete loss of the E2 open reading frame precludes expression of the corresponding protein, resulting in upregulation of the E6 and E7 viral oncoproteins. To better characterize HPV16 infection at the cervical level, viral load, viral DNA integration, and viral early transcript expression (E2, E5, and E6) were analyzed in a series of 158 cervical specimens representative of the full spectrum of cervical disease. Overall, the frequency of early transcript detection varied from 45% to 90% and tended to increase with lesion severity. In addition, the levels of E2, E5, and E6 transcript expression were slightly higher in high-grade lesions than in cervical specimens without abnormalities. Notably, early transcript expression was clearly associated with viral load, and no inverse correlation was found between the expression of E2 and E6 transcripts. No clear association was found between early transcript expression and HPV16 DNA integration, with the exception that samples with a fully integrated HPV16 genome did not harbor E2 or E5 transcripts. In conclusion, early HPV16 transcript expression appears to be associated with viral load rather than lesion grade. From a practical point of view, quantification of HPV16 early transcripts is difficult to translate into a relevant biomarker for cervical cancer screening.
{"title":"The level of expression of HPV16 early transcripts is not associated with the natural history of cervical lesions","authors":"Elise Jacquin, Maëlle Saunier, Quentin Lepiller, Franck Monnien, Frédéric Mauny, Rajeev Ramanah, Xavier Carcopino, Didier Riethmuller, Christiane Mougin, Jean-Luc Prétet","doi":"10.1002/jmv.29875","DOIUrl":"10.1002/jmv.29875","url":null,"abstract":"<p>The natural history of cervical cancer is closely linked to that of high-risk human papillomaviruses (HPV) infection. It is recognized that upon HPV DNA integration, partial or complete loss of the E2 open reading frame precludes expression of the corresponding protein, resulting in upregulation of the E6 and E7 viral oncoproteins. To better characterize HPV16 infection at the cervical level, viral load, viral DNA integration, and viral early transcript expression (E2, E5, and E6) were analyzed in a series of 158 cervical specimens representative of the full spectrum of cervical disease. Overall, the frequency of early transcript detection varied from 45% to 90% and tended to increase with lesion severity. In addition, the levels of E2, E5, and E6 transcript expression were slightly higher in high-grade lesions than in cervical specimens without abnormalities. Notably, early transcript expression was clearly associated with viral load, and no inverse correlation was found between the expression of E2 and E6 transcripts. No clear association was found between early transcript expression and HPV16 DNA integration, with the exception that samples with a fully integrated HPV16 genome did not harbor E2 or E5 transcripts. In conclusion, early HPV16 transcript expression appears to be associated with viral load rather than lesion grade. From a practical point of view, quantification of HPV16 early transcripts is difficult to translate into a relevant biomarker for cervical cancer screening.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108176","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}
Ricarda Plümers, Jens Dreier, Cornelius Knabbe, Tanja Vollmer
In healthy adults, parvovirus B19 (PVB19) typically causes mild symptoms but can lead to severe complications in immunosuppressed individuals or those with high red blood cell turnover. Infection can occur through respiratory transmission or via transfusion, necessitating the testing of blood donations in Germany. Between 2015 and April 2024, we screened 2 105 755 blood donations for PVB19 using polymerase chain reaction. Incidence rates were calculated for three periods: pre-COVID-19 (2015–2020), during the pandemic (2020–2023), and post-COVID-19 (2023–2024). A total of 242 PVB19-positive donations were identified. In the first period, there were 101 positives out of 1 228 361 donations (incidence: 0.83/10 000). In the second period, four positives were found out of 621 222 donations (incidence: 0.06/10 000). In the third period, 137 positives were detected out of 235 088 donations (incidence: 5.35/10 000) with a striking increase of incidence between December 2023 and March 2024 (4.3–21.1/10 000 donations). Most people develop lifelong immunity after infection in childhood but the COVID-19 pandemic interventions, like masks and distancing, correlate with a decline in PVB19 infections in donors indicating an impact of hygiene measures on PVB19 infection rates.
{"title":"Unexpected high incidence of parvovirus B19 nucleic acid detection in German blood donors in the winter/spring season 2023/2024","authors":"Ricarda Plümers, Jens Dreier, Cornelius Knabbe, Tanja Vollmer","doi":"10.1002/jmv.29878","DOIUrl":"https://doi.org/10.1002/jmv.29878","url":null,"abstract":"<p>In healthy adults, parvovirus B19 (PVB19) typically causes mild symptoms but can lead to severe complications in immunosuppressed individuals or those with high red blood cell turnover. Infection can occur through respiratory transmission or via transfusion, necessitating the testing of blood donations in Germany. Between 2015 and April 2024, we screened 2 105 755 blood donations for PVB19 using polymerase chain reaction. Incidence rates were calculated for three periods: pre-COVID-19 (2015–2020), during the pandemic (2020–2023), and post-COVID-19 (2023–2024). A total of 242 PVB19-positive donations were identified. In the first period, there were 101 positives out of 1 228 361 donations (incidence: 0.83/10 000). In the second period, four positives were found out of 621 222 donations (incidence: 0.06/10 000). In the third period, 137 positives were detected out of 235 088 donations (incidence: 5.35/10 000) with a striking increase of incidence between December 2023 and March 2024 (4.3–21.1/10 000 donations). Most people develop lifelong immunity after infection in childhood but the COVID-19 pandemic interventions, like masks and distancing, correlate with a decline in PVB19 infections in donors indicating an impact of hygiene measures on PVB19 infection rates.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.29878","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100022","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}