Pub Date : 2024-12-01Epub Date: 2024-09-09DOI: 10.1080/22221751.2024.2398640
Éric Bergeron, Cheng-Feng Chiang, Michael K Lo, Elif Karaaslan, Syed Moinuddin Satter, Mohammed Ziaur Rahman, Mohammad Enayet Hossain, Wasik Rahman Aquib, Dewan Imtiaz Rahman, Subyeta Binte Sarwar, Joel M Montgomery, John D Klena, Christina F Spiropoulou
Nipah virus (NiV) is an emerging zoonotic RNA virus that can cause fatal respiratory and neurological diseases in animals and humans. Accurate NiV diagnostics and surveillance tools are crucial for the identification of acute and resolved infections and to improve our understanding of NiV transmission and circulation. Here, we have developed and validated a split NanoLuc luciferase NiV glycoprotein (G) biosensor for detecting antibodies in clinical and animal samples. This assay is performed by simply mixing reagents and measuring luminescence, which depends on the complementation of the split NanoLuc luciferase G biosensor following its binding to antibodies. This anti-NiV-G "mix-and-read" assay was validated using the WHO's first international standard for anti-NiV antibodies and more than 700 serum samples from the NiV-endemic country of Bangladesh. Anti-NiV antibodies from survivors persisted for at least 8 years according to both ⍺NiV-G mix-and-read and NiV neutralization assays. The ⍺NiV-G mix-and-read assay sensitivity (98.6%) and specificity (100%) were comparable to anti-NiV IgG ELISA performance but failed to detect anti-NiV antibodies in samples collected less than a week following the appearance of symptoms. Overall, the anti-NiV-G biosensor represents a simple, fast, and reliable tool that could support the expansion of NiV surveillance and retrospective outbreak investigations.
{"title":"Streamlined detection of Nipah virus antibodies using a split NanoLuc biosensor.","authors":"Éric Bergeron, Cheng-Feng Chiang, Michael K Lo, Elif Karaaslan, Syed Moinuddin Satter, Mohammed Ziaur Rahman, Mohammad Enayet Hossain, Wasik Rahman Aquib, Dewan Imtiaz Rahman, Subyeta Binte Sarwar, Joel M Montgomery, John D Klena, Christina F Spiropoulou","doi":"10.1080/22221751.2024.2398640","DOIUrl":"10.1080/22221751.2024.2398640","url":null,"abstract":"<p><p>Nipah virus (NiV) is an emerging zoonotic RNA virus that can cause fatal respiratory and neurological diseases in animals and humans. Accurate NiV diagnostics and surveillance tools are crucial for the identification of acute and resolved infections and to improve our understanding of NiV transmission and circulation. Here, we have developed and validated a split NanoLuc luciferase NiV glycoprotein (G) biosensor for detecting antibodies in clinical and animal samples. This assay is performed by simply mixing reagents and measuring luminescence, which depends on the complementation of the split NanoLuc luciferase G biosensor following its binding to antibodies. This anti-NiV-G \"mix-and-read\" assay was validated using the WHO's first international standard for anti-NiV antibodies and more than 700 serum samples from the NiV-endemic country of Bangladesh. Anti-NiV antibodies from survivors persisted for at least 8 years according to both ⍺NiV-G mix-and-read and NiV neutralization assays. The ⍺NiV-G mix-and-read assay sensitivity (98.6%) and specificity (100%) were comparable to anti-NiV IgG ELISA performance but failed to detect anti-NiV antibodies in samples collected less than a week following the appearance of symptoms. Overall, the anti-NiV-G biosensor represents a simple, fast, and reliable tool that could support the expansion of NiV surveillance and retrospective outbreak investigations.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-09-05DOI: 10.1080/22221751.2024.2396887
Siqiao Liang, Hanlin Liang, Xuemei Huang, Xiaona Liang, Ni Chen, Rong Xiao, Zengtao Luo, Quanfang Chen, Xinxin Zhong, Jingmin Deng, Jie Huang, Meihua Li, Meiling Yang, Wen Zeng, Haijuan Tang, Jing Jiang, Shouming Qin, Zhen Wei, Siyao Wu, Yan Ning, Ke Wang, Fu Cao, Jiujin Zhang, Qing Wei, Chengqiong Xu, Honglin Luo, Jian Song, Pei Li, Xiaokai Feng, Chenlu Yang, Jieping Lei, Hongwei Wang, Bin Cao, Zhiyi He
Anti-interferon-γ autoantibodies (AIGAs) syndrome is susceptible to disseminated opportunistic infections due to increased AIGAs, but its clinical immunological characteristics remain unrecognized. We conducted a prospective cohort study between January 2021 and December 2023, recruiting patients with opportunistic infections who were categorized into AIGAs-positive and AIGAs-negative groups. Clinical immunological data and outcomes were documented. A subset of AIGAs-positive patients received glucocorticoid treatment, and its effectiveness was evaluated. A total of 238 patients were enrolled, with 135 AIGAs-positive and 103 AIGAs-negative patients. AIGAs-positive patients showed higher rates of multiple pathogen dissemination, shorter progression-free survival (PFS), and increased exacerbation frequency. They also showed elevated erythrocyte sedimentation rate (ESR), globulin (GLB), immunoglobulin (Ig)G, IgE, and IgG4 levels. Among the 70 AIGAs-positive patients monitored for at least six months, three subtypes were identified: high AIGAs titer with immune damage, high AIGAs titer without immune damage, and low AIGAs titer without immune damage. Of the 55 patients followed for 1 year, decreasing AIGAs titer and immune indices (GLB, IgG, IgE, IgG4) were observed. Among the 31 patients with high AIGAs titer and immune damage treated with low-dose glucocorticoids at the stable phase, reductions were observed in immune indices and AIGAs titer in 67.74% of cases. In summary, AIGAs-positive patients exhibit infectious and immunological characteristics. Elevated AIGAs, IgG, IgG4, and IgE indicate abnormal immune damages. AIGAs titer generally decrease over time. Stable-phase AIGAs-positive patients can be categorized into three subtypes, with those having high AIGAs titer and increased immune indices potentially benefitting from glucocorticoid treatment.
{"title":"Clinical immunological characteristics of anti-interferon-γ autoantibodies syndrome: a 3 year prospective cohort study.","authors":"Siqiao Liang, Hanlin Liang, Xuemei Huang, Xiaona Liang, Ni Chen, Rong Xiao, Zengtao Luo, Quanfang Chen, Xinxin Zhong, Jingmin Deng, Jie Huang, Meihua Li, Meiling Yang, Wen Zeng, Haijuan Tang, Jing Jiang, Shouming Qin, Zhen Wei, Siyao Wu, Yan Ning, Ke Wang, Fu Cao, Jiujin Zhang, Qing Wei, Chengqiong Xu, Honglin Luo, Jian Song, Pei Li, Xiaokai Feng, Chenlu Yang, Jieping Lei, Hongwei Wang, Bin Cao, Zhiyi He","doi":"10.1080/22221751.2024.2396887","DOIUrl":"10.1080/22221751.2024.2396887","url":null,"abstract":"<p><p>Anti-interferon-γ autoantibodies (AIGAs) syndrome is susceptible to disseminated opportunistic infections due to increased AIGAs, but its clinical immunological characteristics remain unrecognized. We conducted a prospective cohort study between January 2021 and December 2023, recruiting patients with opportunistic infections who were categorized into AIGAs-positive and AIGAs-negative groups. Clinical immunological data and outcomes were documented. A subset of AIGAs-positive patients received glucocorticoid treatment, and its effectiveness was evaluated. A total of 238 patients were enrolled, with 135 AIGAs-positive and 103 AIGAs-negative patients. AIGAs-positive patients showed higher rates of multiple pathogen dissemination, shorter progression-free survival (PFS), and increased exacerbation frequency. They also showed elevated erythrocyte sedimentation rate (ESR), globulin (GLB), immunoglobulin (Ig)G, IgE, and IgG4 levels. Among the 70 AIGAs-positive patients monitored for at least six months, three subtypes were identified: high AIGAs titer with immune damage, high AIGAs titer without immune damage, and low AIGAs titer without immune damage. Of the 55 patients followed for 1 year, decreasing AIGAs titer and immune indices (GLB, IgG, IgE, IgG4) were observed. Among the 31 patients with high AIGAs titer and immune damage treated with low-dose glucocorticoids at the stable phase, reductions were observed in immune indices and AIGAs titer in 67.74% of cases. In summary, AIGAs-positive patients exhibit infectious and immunological characteristics. Elevated AIGAs, IgG, IgG4, and IgE indicate abnormal immune damages. AIGAs titer generally decrease over time. Stable-phase AIGAs-positive patients can be categorized into three subtypes, with those having high AIGAs titer and increased immune indices potentially benefitting from glucocorticoid treatment.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11378669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142043884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-08-26DOI: 10.1080/22221751.2024.2392656
Mohammad Khaja Mafij Uddin, Andrea Maurizio Cabibbe, Rumana Nasrin, Arash Ghodousi, Fahim Alam Nobel, S M Mazidur Rahman, Shahriar Ahmed, Md Fahim Ather, S M Abdur Razzaque, Md Abu Raihan, Pronab Kumar Modak, Jean Luc Berland, Wayne Van Gemert, Sardar Munim Ibna Mohsin, Daniela Maria Cirillo, Sayera Banu
Lack of appropriate early diagnostic tools for drug-resistant tuberculosis (DR-TB) and their incomplete drug susceptibility testing (DST) profiling is concerning for TB disease control. Existing methods, such as phenotypic DST (pDST), are time-consuming, while Xpert MTB/RIF (Xpert) and line probe assay (LPA) are limited to detecting resistance to few drugs. Targeted next-generation sequencing (tNGS) has been recently approved by WHO as an alternative approach for rapid and comprehensive DST. We aimed to investigate the performance and feasibility of tNGS for detecting DR-TB directly from clinical samples in Bangladesh. pDST, LPA and tNGS were performed among 264 sputum samples, either rifampicin-resistant (RR) or rifampicin-sensitive (RS) TB cases confirmed by Xpert assay. Resistotypes of tNGS were compared with pDST, LPA and composite reference standard (CRS, resistant if either pDST or LPA showed a resistant result). tNGS results revealed higher sensitivities for rifampicin (RIF) (99.3%), isoniazid (INH) (96.3%), fluoroquinolones (FQs) (94.4%), and aminoglycosides (AMGs) (100%) but comparatively lower for ethambutol (76.6%), streptomycin (68.7%), ethionamide (56.0%) and pyrazinamide (50.7%) when compared with pDST. The sensitivities of tNGS for INH, RIF, FQs and AMGs were 93.0%, 96.6%, 90.9%, and 100%, respectively and the specificities ranged from 91.3 to 100% when compared with CRS. This proof of concept study, conducted in a high-burden setting demonstrated that tNGS is a valuable tool for identifying DR-TB directly from the clinical specimens. Its feasibility in our laboratory suggests potential implementation and moving tNGS from research settings into clinical settings.
{"title":"Targeted next-generation sequencing of <i>Mycobacterium tuberculosis</i> from patient samples: lessons learned from high drug-resistant burden clinical settings in Bangladesh.","authors":"Mohammad Khaja Mafij Uddin, Andrea Maurizio Cabibbe, Rumana Nasrin, Arash Ghodousi, Fahim Alam Nobel, S M Mazidur Rahman, Shahriar Ahmed, Md Fahim Ather, S M Abdur Razzaque, Md Abu Raihan, Pronab Kumar Modak, Jean Luc Berland, Wayne Van Gemert, Sardar Munim Ibna Mohsin, Daniela Maria Cirillo, Sayera Banu","doi":"10.1080/22221751.2024.2392656","DOIUrl":"10.1080/22221751.2024.2392656","url":null,"abstract":"<p><p>Lack of appropriate early diagnostic tools for drug-resistant tuberculosis (DR-TB) and their incomplete drug susceptibility testing (DST) profiling is concerning for TB disease control. Existing methods, such as phenotypic DST (pDST), are time-consuming, while Xpert MTB/RIF (Xpert) and line probe assay (LPA) are limited to detecting resistance to few drugs. Targeted next-generation sequencing (tNGS) has been recently approved by WHO as an alternative approach for rapid and comprehensive DST. We aimed to investigate the performance and feasibility of tNGS for detecting DR-TB directly from clinical samples in Bangladesh. pDST, LPA and tNGS were performed among 264 sputum samples, either rifampicin-resistant (RR) or rifampicin-sensitive (RS) TB cases confirmed by Xpert assay. Resistotypes of tNGS were compared with pDST, LPA and composite reference standard (CRS, resistant if either pDST or LPA showed a resistant result). tNGS results revealed higher sensitivities for rifampicin (RIF) (99.3%), isoniazid (INH) (96.3%), fluoroquinolones (FQs) (94.4%), and aminoglycosides (AMGs) (100%) but comparatively lower for ethambutol (76.6%), streptomycin (68.7%), ethionamide (56.0%) and pyrazinamide (50.7%) when compared with pDST. The sensitivities of tNGS for INH, RIF, FQs and AMGs were 93.0%, 96.6%, 90.9%, and 100%, respectively and the specificities ranged from 91.3 to 100% when compared with CRS. This proof of concept study, conducted in a high-burden setting demonstrated that tNGS is a valuable tool for identifying DR-TB directly from the clinical specimens. Its feasibility in our laboratory suggests potential implementation and moving tNGS from research settings into clinical settings.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11348811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-09-01DOI: 10.1080/22221751.2024.2386136
Pallavi Singh, Pratap Vydyam, Tiffany Fang, Karel Estrada, Luis Miguel Gonzalez, Ricardo Grande, Madelyn Kumar, Sakshar Chakravarty, Vincent Berry, Vincent Ranwez, Bernard Carcy, Delphine Depoix, Sergio Sánchez, Emmanuel Cornillot, Steven Abel, Loic Ciampossin, Todd Lenz, Omar Harb, Alejandro Sanchez-Flores, Estrella Montero, Karine G Le Roch, Stefano Lonardi, Choukri Ben Mamoun
Babesiosis, caused by protozoan parasites of the genus Babesia, is an emerging tick-borne disease of significance for both human and animal health. Babesia parasites infect erythrocytes of vertebrate hosts where they develop and multiply rapidly to cause the pathological symptoms associated with the disease. The identification of new Babesia species underscores the ongoing risk of zoonotic pathogens capable of infecting humans, a concern amplified by anthropogenic activities and environmental changes. One such pathogen, Babesia MO1, previously implicated in severe cases of human babesiosis in the United States, was initially considered a subspecies of B. divergens, the predominant agent of human babesiosis in Europe. Here we report comparative multiomics analyses of B. divergens and B. MO1 that offer insight into their biology and evolution. Our analysis shows that despite their highly similar genomic sequences, substantial genetic and genomic divergence occurred throughout their evolution resulting in major differences in gene functions, expression and regulation, replication rates and susceptibility to antiparasitic drugs. Furthermore, both pathogens have evolved distinct classes of multigene families, crucial for their pathogenicity and adaptation to specific mammalian hosts. Leveraging genomic information for B. MO1, B. divergens, and other members of the Babesiidae family within Apicomplexa provides valuable insights into the evolution, diversity, and virulence of these parasites. This knowledge serves as a critical tool in preemptively addressing the emergence and rapid transmission of more virulent strains.
摘要 由巴贝斯虫属原生动物寄生虫引起的巴贝斯虫病是一种新出现的蜱媒疾病,对人类和动物健康都具有重要意义。巴贝西亚原虫感染脊椎动物宿主的红细胞,并在红细胞中迅速发育和繁殖,从而引起与该疾病相关的病理症状。巴贝西亚原虫新物种的发现凸显了能够感染人类的人畜共患病原体的持续风险,而人类活动和环境变化加剧了这种风险。其中一种病原体是巴贝西亚原虫 MO1,它曾与美国的严重人类巴贝西亚原虫病病例有牵连,最初被认为是巴贝西亚原虫的一个亚种,而巴贝西亚原虫是欧洲人类巴贝西亚原虫病的主要病原体。在此,我们报告了对 B. divergens 和 B. MO1 进行的多组学比较分析,以深入了解它们的生物学和进化情况。我们的分析表明,尽管它们的基因组序列高度相似,但在整个进化过程中发生了巨大的遗传和基因组差异,导致基因功能、表达和调控、复制率和对抗原药物的敏感性等方面存在重大差异。此外,这两种病原体都进化出了不同类别的多基因家族,这对它们的致病性和对特定哺乳动物宿主的适应性至关重要。利用 B. MO1、B. Divergens 和 Apicomplexa 中 Babesiidae 家族其他成员的基因组信息,可以深入了解这些寄生虫的进化、多样性和毒力。这些知识是先发制人地应对毒性更强的菌株的出现和快速传播的重要工具。
{"title":"Insights into the evolution, virulence and speciation of <i>Babesia MO1</i> and <i>Babesia divergens</i> through multiomics analyses.","authors":"Pallavi Singh, Pratap Vydyam, Tiffany Fang, Karel Estrada, Luis Miguel Gonzalez, Ricardo Grande, Madelyn Kumar, Sakshar Chakravarty, Vincent Berry, Vincent Ranwez, Bernard Carcy, Delphine Depoix, Sergio Sánchez, Emmanuel Cornillot, Steven Abel, Loic Ciampossin, Todd Lenz, Omar Harb, Alejandro Sanchez-Flores, Estrella Montero, Karine G Le Roch, Stefano Lonardi, Choukri Ben Mamoun","doi":"10.1080/22221751.2024.2386136","DOIUrl":"10.1080/22221751.2024.2386136","url":null,"abstract":"<p><p>Babesiosis, caused by protozoan parasites of the genus <i>Babesia</i>, is an emerging tick-borne disease of significance for both human and animal health. <i>Babesia</i> parasites infect erythrocytes of vertebrate hosts where they develop and multiply rapidly to cause the pathological symptoms associated with the disease. The identification of new <i>Babesia</i> species underscores the ongoing risk of zoonotic pathogens capable of infecting humans, a concern amplified by anthropogenic activities and environmental changes. One such pathogen, <i>Babesia MO1</i>, previously implicated in severe cases of human babesiosis in the United States, was initially considered a subspecies of <i>B. divergens</i>, the predominant agent of human babesiosis in Europe. Here we report comparative multiomics analyses of <i>B. divergens</i> and <i>B. MO1</i> that offer insight into their biology and evolution. Our analysis shows that despite their highly similar genomic sequences, substantial genetic and genomic divergence occurred throughout their evolution resulting in major differences in gene functions, expression and regulation, replication rates and susceptibility to antiparasitic drugs. Furthermore, both pathogens have evolved distinct classes of multigene families, crucial for their pathogenicity and adaptation to specific mammalian hosts. Leveraging genomic information for <i>B. MO1</i>, <i>B. divergens</i>, and other members of the Babesiidae family within Apicomplexa provides valuable insights into the evolution, diversity, and virulence of these parasites. This knowledge serves as a critical tool in preemptively addressing the emergence and rapid transmission of more virulent strains.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11370697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2023-12-30DOI: 10.1080/22221751.2023.2281356
Konner Cool, Natasha N Gaudreault, Jessie D Trujillo, Igor Morozov, Chester D McDowell, Dashzeveg Bold, Taeyong Kwon, Velmurugan Balaraman, Patricia Assato, Daniel W Madden, Emily Mantlo, Jayme Souza-Neto, Franco Matias-Ferreyra, Jaime Retallick, Gagandeep Singh, Michael Schotsaert, Mariano Carossino, Udeni B R Balasuriya, William C Wilson, Roman M Pogranichniy, Adolfo García-Sastre, Juergen A Richt
Since emerging in late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has repeatedly crossed the species barrier with natural infections reported in various domestic and wild animal species. The emergence and global spread of SARS-CoV-2 variants of concern (VOCs) has expanded the range of susceptible host species. Previous experimental infection studies in cattle using Wuhan-like SARS-CoV-2 isolates suggested that cattle were not likely amplifying hosts for SARS-CoV-2. However, SARS-CoV-2 sero- and RNA-positive cattle have since been identified in Europe, India, and Africa. Here, we investigated the susceptibility and transmission of the Delta and Omicron SARS-CoV-2 VOCs in cattle. Eight Holstein calves were co-infected orally and intranasally with a mixed inoculum of SARS-CoV-2 VOCs Delta and Omicron BA.2. Twenty-four hours post-challenge, two sentinel calves were introduced to evaluate virus transmission. The co-infection resulted in a high proportion of calves shedding SARS-CoV-2 RNA at 1- and 2-days post-challenge (DPC). Extensive tissue distribution of SARS-CoV-2 RNA was observed at 3 and 7 DPC and infectious virus was recovered from two calves at 3 DPC. Next-generation sequencing revealed that only the SARS-CoV-2 Delta variant was detected in clinical samples and tissues. Similar to previous experimental infection studies in cattle, we observed only limited seroconversion and no clear evidence of transmission to sentinel calves. Together, our findings suggest that cattle are more permissive to infection with SARS-CoV-2 Delta than Omicron BA.2 and Wuhan-like isolates but, in the absence of horizontal transmission, are not likely to be reservoir hosts for currently circulating SARS-CoV-2 variants.
{"title":"Experimental co-infection of calves with SARS-CoV-2 Delta and Omicron variants of concern.","authors":"Konner Cool, Natasha N Gaudreault, Jessie D Trujillo, Igor Morozov, Chester D McDowell, Dashzeveg Bold, Taeyong Kwon, Velmurugan Balaraman, Patricia Assato, Daniel W Madden, Emily Mantlo, Jayme Souza-Neto, Franco Matias-Ferreyra, Jaime Retallick, Gagandeep Singh, Michael Schotsaert, Mariano Carossino, Udeni B R Balasuriya, William C Wilson, Roman M Pogranichniy, Adolfo García-Sastre, Juergen A Richt","doi":"10.1080/22221751.2023.2281356","DOIUrl":"10.1080/22221751.2023.2281356","url":null,"abstract":"<p><p>Since emerging in late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has repeatedly crossed the species barrier with natural infections reported in various domestic and wild animal species. The emergence and global spread of SARS-CoV-2 variants of concern (VOCs) has expanded the range of susceptible host species. Previous experimental infection studies in cattle using Wuhan-like SARS-CoV-2 isolates suggested that cattle were not likely amplifying hosts for SARS-CoV-2. However, SARS-CoV-2 sero- and RNA-positive cattle have since been identified in Europe, India, and Africa. Here, we investigated the susceptibility and transmission of the Delta and Omicron SARS-CoV-2 VOCs in cattle. Eight Holstein calves were co-infected orally and intranasally with a mixed inoculum of SARS-CoV-2 VOCs Delta and Omicron BA.2. Twenty-four hours post-challenge, two sentinel calves were introduced to evaluate virus transmission. The co-infection resulted in a high proportion of calves shedding SARS-CoV-2 RNA at 1- and 2-days post-challenge (DPC). Extensive tissue distribution of SARS-CoV-2 RNA was observed at 3 and 7 DPC and infectious virus was recovered from two calves at 3 DPC. Next-generation sequencing revealed that only the SARS-CoV-2 Delta variant was detected in clinical samples and tissues. Similar to previous experimental infection studies in cattle, we observed only limited seroconversion and no clear evidence of transmission to sentinel calves. Together, our findings suggest that cattle are more permissive to infection with SARS-CoV-2 Delta than Omicron BA.2 and Wuhan-like isolates but, in the absence of horizontal transmission, are not likely to be reservoir hosts for currently circulating SARS-CoV-2 variants.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":null,"pages":null},"PeriodicalIF":13.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10763854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71479446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-05-31DOI: 10.1080/22221751.2024.2359004
Qian Wang, Yicheng Guo, Logan T Schwanz, Ian A Mellis, Yiwei Sun, Yiming Qu, Guillaume Urtecho, Riccardo Valdez, Emily Stoneman, Aubree Gordon, Harris H Wang, David D Ho, Lihong Liu
As SARS-CoV-2 continues to spread and mutate, tracking the viral evolutionary trajectory and understanding the functional consequences of its mutations remain crucial. Here, we characterized the antibody evasion, ACE2 receptor engagement, and viral infectivity of the highly mutated SARS-CoV-2 Omicron subvariant BA.2.87.1. Compared with other Omicron subvariants, including EG.5.1 and the current predominant JN.1, BA.2.87.1 exhibits less immune evasion, reduced viral receptor engagement, and comparable infectivity in Calu-3 lung cells. Intriguingly, two large deletions (Δ15-26 and Δ136-146) in the N-terminal domain (NTD) of the spike protein facilitate subtly increased antibody evasion but significantly diminish viral infectivity. Collectively, our data support the announcement by the USA CDC that the public health risk posed by BA.2.87.1 appears to be low.
{"title":"SARS-CoV-2 omicron BA.2.87.1 exhibits higher susceptibility to serum neutralization than EG.5.1 and JN.1.","authors":"Qian Wang, Yicheng Guo, Logan T Schwanz, Ian A Mellis, Yiwei Sun, Yiming Qu, Guillaume Urtecho, Riccardo Valdez, Emily Stoneman, Aubree Gordon, Harris H Wang, David D Ho, Lihong Liu","doi":"10.1080/22221751.2024.2359004","DOIUrl":"10.1080/22221751.2024.2359004","url":null,"abstract":"<p><p>As SARS-CoV-2 continues to spread and mutate, tracking the viral evolutionary trajectory and understanding the functional consequences of its mutations remain crucial. Here, we characterized the antibody evasion, ACE2 receptor engagement, and viral infectivity of the highly mutated SARS-CoV-2 Omicron subvariant BA.2.87.1. Compared with other Omicron subvariants, including EG.5.1 and the current predominant JN.1, BA.2.87.1 exhibits less immune evasion, reduced viral receptor engagement, and comparable infectivity in Calu-3 lung cells. Intriguingly, two large deletions (Δ15-26 and Δ136-146) in the N-terminal domain (NTD) of the spike protein facilitate subtly increased antibody evasion but significantly diminish viral infectivity. Collectively, our data support the announcement by the USA CDC that the public health risk posed by BA.2.87.1 appears to be low.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":null,"pages":null},"PeriodicalIF":13.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11146261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141079989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-06-04DOI: 10.1080/22221751.2024.2356146
Siquan Shen, Chengkang Tang, Weiwei Yang, Li Ding, Renru Han, Qingyu Shi, Yan Guo, Dandan Yin, Fupin Hu
Ceftazidime-avibactam (CZA) is employed for the treatment of infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-KP). Resistance to CZA is frequently linked to point mutations in the blaKPC. We conducted in vitro simulations of in vivo blaKPC mutations using CZA. Four pre-therapy KPC-KP isolates (K1, K2, K3, and K4) were evaluated, all initially exhibited susceptibility to CZA and produced KPC-2. The crucial distinction was that following CZA treatment, the blaKPC-2 mutated in K1, K2, and K3, rendering them resistant to CZA, while K4 achieved microbiological clearance, and blaKPC-2 remained unaltered. The induction assay identified various blaKPC-2 variants, including blaKPC-25, blaKPC-127, blaKPC-100, blaKPC-128, blaKPC-137, blaKPC-138, blaKPC-144 and blaKPC-180. Our findings suggest that the resistance of KPC-KP to CZA primarily results from the emergence of KPC variants, complemented by increased blaKPC expression. A close correlation exists between avibactam concentration and the rate of increased CZA minimum Inhibitory concentration, as well as blaKPC mutation. Inadequate avibactam concentration is more likely to induce resistance in strains against CZA, there is also a higher likelihood of mutation in the blaKPC-2 and the optimal avibactam ratio remains to be determined. Simultaneously, we selected a blaKPC-33-producing K. pneumoniae strain (mutated from blaKPC-2) and induced it with imipenem and meropenem, respectively. The blaKPC-2 was detected during the process, indicating that the mutation is reversible. Clinical use of carbapenems to treat KPC variant strains increases the risk of infection, as the gene can mutate back to blaKPC-2, rendering the strain even more cross-resistant to carbapenems and CZA.
{"title":"In vitro mimicry of in vivo KPC mutations by ceftazidime-avibactam: phenotypes, mechanisms, genetic structure and kinetics of enzymatic hydrolysis.","authors":"Siquan Shen, Chengkang Tang, Weiwei Yang, Li Ding, Renru Han, Qingyu Shi, Yan Guo, Dandan Yin, Fupin Hu","doi":"10.1080/22221751.2024.2356146","DOIUrl":"10.1080/22221751.2024.2356146","url":null,"abstract":"<p><p>Ceftazidime-avibactam (CZA) is employed for the treatment of infections caused by <i>Klebsiella pneumoniae</i> carbapenemase-producing <i>K. pneumoniae</i> (KPC-KP). Resistance to CZA is frequently linked to point mutations in the <i>bla</i><sub>KPC</sub>. We conducted <i>in vitro</i> simulations of <i>in vivo bla</i><sub>KPC</sub> mutations using CZA. Four pre-therapy KPC-KP isolates (K1, K2, K3, and K4) were evaluated, all initially exhibited susceptibility to CZA and produced KPC-2. The crucial distinction was that following CZA treatment, the <i>bla</i><sub>KPC-2</sub> mutated in K1, K2, and K3, rendering them resistant to CZA, while K4 achieved microbiological clearance, and <i>bla</i><sub>KPC-2</sub> remained unaltered. The induction assay identified various <i>bla</i><sub>KPC-2</sub> variants, including <i>bla</i><sub>KPC-25</sub>, <i>bla</i><sub>KPC-127</sub>, <i>bla</i><sub>KPC-100</sub>, <i>bla</i><sub>KPC-128</sub>, <i>bla</i><sub>KPC-137</sub>, <i>bla</i><sub>KPC-138</sub>, <i>bla</i><sub>KPC-144</sub> and <i>bla</i><sub>KPC-180</sub>. Our findings suggest that the resistance of KPC-KP to CZA primarily results from the emergence of KPC variants, complemented by increased <i>bla</i><sub>KPC</sub> expression. A close correlation exists between avibactam concentration and the rate of increased CZA minimum Inhibitory concentration, as well as <i>bla</i><sub>KPC</sub> mutation. Inadequate avibactam concentration is more likely to induce resistance in strains against CZA, there is also a higher likelihood of mutation in the <i>bla</i><sub>KPC-2</sub> and the optimal avibactam ratio remains to be determined. Simultaneously, we selected a <i>bla</i><sub>KPC-33</sub>-producing <i>K. pneumoniae</i> strain (mutated from <i>bla</i><sub>KPC-2</sub>) and induced it with imipenem and meropenem, respectively. The <i>bla</i><sub>KPC-2</sub> was detected during the process, indicating that the mutation is reversible. Clinical use of carbapenems to treat KPC variant strains increases the risk of infection, as the gene can mutate back to <i>bla</i><sub>KPC-2</sub>, rendering the strain even more cross-resistant to carbapenems and CZA.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":null,"pages":null},"PeriodicalIF":13.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11151810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140921677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The discovery of promising cytokines and clarification of their immunological mechanisms in controlling the intracellular fate of Mycobacterium tuberculosis (Mtb) are necessary to identify effective diagnostic biomarkers and therapeutic targets. To escape immune clearance, Mtb can manipulate and inhibit the normal host process of phagosome maturation. Phagosome maturation arrest by Mtb involves multiple effectors and much remains unknown about this important aspect of Mtb pathogenesis. In this study, we found that interleukin 16 (IL-16) is elevated in the serum samples of Tuberculosis (TB) patients and can serve as a specific target for treatment TB. There was a significant difference in IL-16 levels among active TB, latent TB infection (LTBI), and non-TB patients. This study first revealed that macrophages are the major source of IL-16 production in response to Mtb infection, and elucidated that IL-16 can promote Mtb intracellular survival by inhibiting phagosome maturation and suppressing the expression of Rev-erbα which can inhibit IL-10 secretion. The experiments using zebrafish larvae infected with M. marinum and mice challenged with H37Rv demonstrated that reducing IL-16 levels resulted in less severe pathology and improved survival, respectively. In conclusion, this study provided direct evidence that Mtb hijacks the host macrophages-derived interleukin 16 to enhance intracellular growth. It is suggesting the immunosuppressive role of IL-16 during Mtb infection, supporting IL-16 as a promising therapeutic target.
{"title":"<i>Mycobacterium tuberculosis</i> hijacks host macrophages-derived interleukin 16 to block phagolysosome maturation for enhancing intracellular growth.","authors":"Haibo Su, Shufeng Weng, Liulin Luo, Qin Sun, Taiyue Lin, Huixia Ma, Yumo He, Jing Wu, Honghai Wang, Wenhong Zhang, Ying Xu","doi":"10.1080/22221751.2024.2322663","DOIUrl":"10.1080/22221751.2024.2322663","url":null,"abstract":"<p><p>The discovery of promising cytokines and clarification of their immunological mechanisms in controlling the intracellular fate of <i>Mycobacterium tuberculosis</i> (Mtb) are necessary to identify effective diagnostic biomarkers and therapeutic targets. To escape immune clearance, Mtb can manipulate and inhibit the normal host process of phagosome maturation. Phagosome maturation arrest by Mtb involves multiple effectors and much remains unknown about this important aspect of Mtb pathogenesis. In this study, we found that interleukin 16 (IL-16) is elevated in the serum samples of Tuberculosis (TB) patients and can serve as a specific target for treatment TB. There was a significant difference in IL-16 levels among active TB, latent TB infection (LTBI), and non-TB patients. This study first revealed that macrophages are the major source of IL-16 production in response to Mtb infection, and elucidated that IL-16 can promote Mtb intracellular survival by inhibiting phagosome maturation and suppressing the expression of Rev-erbα which can inhibit IL-10 secretion. The experiments using zebrafish larvae infected with <i>M. marinum</i> and mice challenged with H37Rv demonstrated that reducing IL-16 levels resulted in less severe pathology and improved survival, respectively. In conclusion, this study provided direct evidence that Mtb hijacks the host macrophages-derived interleukin 16 to enhance intracellular growth. It is suggesting the immunosuppressive role of IL-16 during Mtb infection, supporting IL-16 as a promising therapeutic target.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":null,"pages":null},"PeriodicalIF":13.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10911244/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139912341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Recently, an outbreak of highly pathogenic avian influenza A (H5N1), which carries the clade 2.3.4.4b hemagglutinin (HA) gene and has been prevalent among North American bird populations since the winter of 2021, was reported in dairy cows in the United States. As of 24 May 2024, the virus has affected 63 dairy herds across nine states and has resulted in two human infections. The virus causes unusual symptoms in dairy cows, including an unexpected drop in milk production, and thick colostrum-like milk. Notably, The US Food and Drug Administration reported that around 20% of tested retail milk samples contained H5N1 viruses, with a higher percentage of positive results from regions with infected cattle herds. Data are scant regarding how effectively pasteurization inactivates the H5N1 virus in milk. Therefore, in this study, we evaluated the thermal stability of the H5 clade 2.3.4.4b viruses, along with one human H3N2 virus and other influenza subtype viruses, including H1, H3, H7, H9, and H10 subtype viruses. We also assessed the effectiveness of pasteurization in inactivating these viruses. We found that the avian H3 virus exhibits the highest thermal stability, whereas the H5N1 viruses that belong to clade 2.3.4.4b display moderate thermal stability. Importantly, our data provide direct evidence that the standard pasteurization methods used by dairy companies are effective in inactivating all tested subtypes of influenza viruses in raw milk. Our findings indicate that thermally pasteurized milk products do not pose a safety risk to consumers.
{"title":"Does pasteurization inactivate bird flu virus in milk?","authors":"Pengfei Cui, Yichao Zhuang, Yaping Zhang, Lei Chen, Puze Chen, Jiaqi Li, Lulu Feng, Qin Chen, Fei Meng, Huanliang Yang, Yongping Jiang, Guohua Deng, Jianzhong Shi, Hualan Chen, Huihui Kong","doi":"10.1080/22221751.2024.2364732","DOIUrl":"10.1080/22221751.2024.2364732","url":null,"abstract":"<p><p>Recently, an outbreak of highly pathogenic avian influenza A (H5N1), which carries the clade 2.3.4.4b hemagglutinin (HA) gene and has been prevalent among North American bird populations since the winter of 2021, was reported in dairy cows in the United States. As of 24 May 2024, the virus has affected 63 dairy herds across nine states and has resulted in two human infections. The virus causes unusual symptoms in dairy cows, including an unexpected drop in milk production, and thick colostrum-like milk. Notably, The US Food and Drug Administration reported that around 20% of tested retail milk samples contained H5N1 viruses, with a higher percentage of positive results from regions with infected cattle herds. Data are scant regarding how effectively pasteurization inactivates the H5N1 virus in milk. Therefore, in this study, we evaluated the thermal stability of the H5 clade 2.3.4.4b viruses, along with one human H3N2 virus and other influenza subtype viruses, including H1, H3, H7, H9, and H10 subtype viruses. We also assessed the effectiveness of pasteurization in inactivating these viruses. We found that the avian H3 virus exhibits the highest thermal stability, whereas the H5N1 viruses that belong to clade 2.3.4.4b display moderate thermal stability. Importantly, our data provide direct evidence that the standard pasteurization methods used by dairy companies are effective in inactivating all tested subtypes of influenza viruses in raw milk. Our findings indicate that thermally pasteurized milk products do not pose a safety risk to consumers.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":null,"pages":null},"PeriodicalIF":13.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11182070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141237140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}