Emerging Microbes & Infections最新文献

{"title":"An extracellular humanized IFNAR immunocompetent mouse model for analyses of human interferon alpha and subtypes.","authors":"Yumeng Li, Asha Ashuo, Menghan Hao, Yaming Li, Jianyu Ye, Jiangxia Liu, Ting Hua, Zhong Fang, Jianhua Li, Zhenghong Yuan, Jieliang Chen","doi":"10.1080/22221751.2023.2287681","DOIUrl":"10.1080/22221751.2023.2287681","url":null,"abstract":"<p><p>Type I interferons (IFN-Is) have key roles in immune defense and treatments for various diseases, including chronic hepatitis B virus (HBV) infection. All IFN-Is signal through a shared IFN-I heterodimeric receptor complex comprising IFN-α receptor 1 (IFNAR1) and IFNAR2 subunits, but differences in antiviral and immunomodulatory responses among IFN-I subtypes remain largely unknown. Because the IFN-IFNAR interactions are species-specific, mice exhibit weak responses to human IFN-I. To more fully characterize the actions of human IFN-α and its subtypes <i>in vivo</i>, a gene targeting strategy was employed to generate gene knock-in mice with extracellular-humanized IFNAR1/2 (IFNAR-hEC) in the C57BL/6N strain. IFNAR-hEC mice actively responded to human IFN-I, and endogenous mouse IFN-I signalling remained active in heterozygous mice (<i>Ifnar</i>^hEC/+). Analyses of IFNAR-hEC mice and isolated cells showed that human IFN-α2 and α14 subtypes exerted differential effect on the activation of JAK-STAT signalling and immune responses. Compared with IFN-α2, IFN-α14 induced greater activation of STAT1/2 and IFN-stimulated genes, synergistically elicited IFN-α and -γ signalling, and induced higher numbers of antigen-specific CD8⁺ T cells. Moreover, IFNAR-hEC mice with HBV replication displayed long-term viral suppression upon treatment with the clinically-used PEGylated hIFN-α2. These results indicate that IFNAR-hEC mice may be useful for elucidating antiviral and immunomodulatory functions of human IFN-Is and for conducting preclinical studies. A better understanding of the distinct activities of IFN-α subtypes can provide insights concerning the development of improved IFN-based therapy.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2287681"},"PeriodicalIF":8.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10810641/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138294929","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}

{"title":"The T120P or M172V mutation on <i>rv2172c</i> confers high level <i>para</i>-aminosalicylic acid resistance in <i>Mycobacterium tuberculosis</i>.","authors":"Jin-Tian Xu, Ji-Fang Yu, Tao Cheng, Ao Feng, Ping Yang, Jing Gu, Hong-Jun Yu, Jiao-Yu Deng","doi":"10.1080/22221751.2024.2374030","DOIUrl":"10.1080/22221751.2024.2374030","url":null,"abstract":"<p><p>Although <i>para</i>-aminosalicylic acid (PAS) has been used to treat tuberculosis for decades, mechanisms of resistance to this drug in <i>Mycobacterium tuberculosis</i> (<i>M. tuberculosis</i>) clinical isolates have not been thoroughly investigated. Previously, we found that decreased methylenetetrahydrofolate reductase (MTHFR) activity of Rv2172c led to increased sensitivity to antifolates in <i>M. tuberculosis</i>. In this study, we collected the genome-sequencing data of 173 PAS-resistant and 803 PAS-sensitive clinical isolates and analyzed <i>rv2172c</i> mutations in those 976 isolates. The results showed that two mutations (T120P and M172V) on <i>rv2172c</i> could be identified in a certain proportion (6.36%) of PAS-resistant isolates. The results of AlphaFold2 prediction indicated that the T120P or M172V mutation might affect the enzymatic activity of Rv2172c by influencing nicotinamide adenine dinucleotide (NADH) binding, and this was verified by subsequent biochemical analysis, demonstrating the role of residues Thr120 and Met172 on NADH binding and enzymatic activity of Rv2172c. In addition, the effect of <i>rv2172c</i> T120P or M172V mutation on methionine production and PAS resistance was determined in <i>M. tuberculosis</i>. The results showed that both T120P and M172V mutations caused increased intracellular methionine concentrations and high level PAS resistance. In summary, we discovered new molecular markers and also a novel mechanism of PAS resistance in <i>M. tuberculosis</i> clinical isolates and broadened the understanding of the NADH-dependent MTHFR catalytic mechanism of Rv2172c in <i>M. tuberculosis</i>, which will facilitate the molecular diagnosis of PAS resistance and also the development of new drugs targeting Rv2172c.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2374030"},"PeriodicalIF":8.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11271092/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141633042","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}

{"title":"Differential susceptibility of geographically distinct <i>Ixodes ricinus</i> populations to tick-borne encephalitis virus and louping ill virus.","authors":"Julian W Bakker, Helen J Esser, Hein Sprong, Gert-Jan Godeke, Tabitha E Hoornweg, Willem F de Boer, Gorben P Pijlman, Constantianus J M Koenraadt","doi":"10.1080/22221751.2024.2321992","DOIUrl":"10.1080/22221751.2024.2321992","url":null,"abstract":"<p><p>Tick-borne encephalitis virus (TBEV) is an emerging pathogen in the Netherlands. Multiple divergent viral strains are circulating and the focal distribution of TBEV remains poorly understood. This may, however, be explained by differences in the susceptibility of tick populations for specific viruses and viral strains, and by viral strains having higher infection success in their local tick population. We investigated this hypothesis by exposing Dutch <i>Ixodes ricinus</i> ticks to two different TBEV strains: TBEV-NL from the Netherlands and TBEV-Neudoerfl from Austria. In addition, we exposed ticks to louping Ill virus (LIV), which is endemic to large parts of the United Kingdom and Ireland, but has not been reported in the Netherlands. Ticks were collected from two locations in the Netherlands: one location without evidence of TBEV circulation and one location endemic for the TBEV-NL strain. Ticks were infected in a biosafety level 3 laboratory using an artificial membrane feeding system. Ticks collected from the region without evidence of TBEV circulation had lower infection rates for TBEV-NL as compared to TBEV-Neudoerfl. <i>Vice versa</i>, ticks collected from the TBEV-NL endemic region had higher infection rates for TBEV-NL compared to TBEV-Neudoerfl. In addition, LIV infection rates were much lower in Dutch ticks compared to TBEV, which may explain why LIV is not present in the Netherlands. Our findings show that ticks from two distinct geographical populations differ in their susceptibility to TBEV strains, which could be the result of differences in the genetic background of the tick populations.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"13 1","pages":"2321992"},"PeriodicalIF":13.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10946273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140130981","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}

{"title":"OXA-48-like carbapenemases in <i>Proteus mirabilis</i> - novel genetic environments and a challenge for detection.","authors":"Janko Sattler, Janina Noster, Yvonne Stelzer, Martina Spille, Sina Schäfer, Kyriaki Xanthopoulou, Julian Sommer, Jonathan Jantsch, Silke Peter, Stephan Göttig, Sören G Gatermann, Axel Hamprecht","doi":"10.1080/22221751.2024.2353310","DOIUrl":"10.1080/22221751.2024.2353310","url":null,"abstract":"<p><p>OXA-48-like enzymes represent the most frequently detected carbapenemases in Enterobacterales in Western Europe, North Africa and the Middle East. In contrast to other species, the presence of OXA-48-like in <i>Proteus mirabilis</i> leads to an unusually susceptible phenotype with low MICs for carbapenems and piperacillin-tazobactam, which is easily missed in the diagnostic laboratory. So far, there is little data available on the genetic environments of the corresponding genes, <i>bla</i>_OXA-48-like, in <i>P. mirabilis.</i> In this study susceptibility phenotypes and genomic data of 13 OXA-48-like-producing <i>P. mirabilis</i> were investigated (OXA-48, <i>n</i> = 9; OXA-181, <i>n</i> = 3; OXA-162, <i>n</i> = 1). Ten isolates were susceptible to meropenem and ertapenem and three isolates were susceptible to piperacillin-tazobactam. The gene <i>bla</i>_OXA-48 was chromosomally located in 7/9 isolates. Thereof, in three isolates <i>bla</i>_OXA-48 was inserted into a <i>P. mirabilis</i> genomic island. Of the three isolates harbouring <i>bla</i>_OXA-181 one was located on an IncX3 plasmid and two were located on a novel MOB_F plasmid, pOXA-P12, within the new transposon Tn<i>7713</i>. In 5/6 isolates with plasmidic location of <i>bla</i>_OXA-48-like, the plasmids could conjugate to <i>E. coli</i> recipients <i>in vitro</i>. <i>Vice versa</i>, <i>bla</i>_OXA-48-carrying plasmids could conjugate from other Enterobacterales into a <i>P. mirabilis</i> recipient. These data show a high diversity of <i>bla</i>_OXA-48-like genetic environments compared to other Enterobacterales, where genetic environments are quite homogenous. Given the difficult-to-detect phenotype of OXA-48-like-producing <i>P. mirabilis</i> and the location of <i>bla</i>_OXA-48-like on mobile genetic elements<i>,</i> it is likely that OXA-48-like-producing <i>P. mirabilis</i> can disseminate, escape most surveillance systems, and contribute to a hidden spread of OXA-48-like.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2353310"},"PeriodicalIF":13.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11123474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140856757","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}

{"title":"Letter to the editor: lansoprazole interferes with fungal respiration and acts synergistically with amphotericin B against multidrug-resistant <i>Candida auris</i>.","authors":"Meng Zhu, Hongyang Wang, Yongsheng Zhang, Fuzhen Pan","doi":"10.1080/22221751.2024.2356144","DOIUrl":"10.1080/22221751.2024.2356144","url":null,"abstract":"<p><p>The study investigates the potential of lansoprazole, a proton pump inhibitor, to interfere with fungal respiration and enhance the antifungal activity of amphotericin B against multidrug-resistant Candida auris. The authors administered lansoprazole at concentrations significantly higher than typical therapeutic doses, which demonstrated promising results but also raised concerns about potential toxicity. We suggest incorporating a control group, monitoring toxicity indicators, performing pathological examinations, and conducting cellular assays to improve the study's rigor and reliability. We also highlight the need for further research into the mechanisms of lansoprazole's antifungal activity, its long-term effects on amphotericin B resistance, and potential drug-drug interactions with amphotericin B. Addressing these concerns is crucial for the clinical translation of lansoprazole as an adjuvant to amphotericin B.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2356144"},"PeriodicalIF":13.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11182049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140921681","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}

{"title":"Prediction models for COVID-19 disease outcomes.","authors":"Cynthia Y Tang, Cheng Gao, Kritika Prasai, Tao Li, Shreya Dash, Jane A McElroy, Jun Hang, Xiu-Feng Wan","doi":"10.1080/22221751.2024.2361791","DOIUrl":"10.1080/22221751.2024.2361791","url":null,"abstract":"<p><p>SARS-CoV-2 has caused over 6.9 million deaths and continues to produce lasting health consequences. COVID-19 manifests broadly from no symptoms to death. In a retrospective cross-sectional study, we developed personalized risk assessment models that predict clinical outcomes for individuals with COVID-19 and inform targeted interventions. We sequenced viruses from SARS-CoV-2-positive nasopharyngeal swab samples between July 2020 and July 2022 from 4450 individuals in Missouri and retrieved associated disease courses, clinical history, and urban-rural classification. We integrated this data to develop machine learning-based predictive models to predict hospitalization, ICU admission, and long COVID.The mean age was 38.3 years (standard deviation = 21.4) with 55.2% (<i>N</i> = 2453) females and 44.8% (<i>N</i> = 1994) males (not reported, <i>N</i> = 4). Our analyses revealed a comprehensive set of predictors for each outcome, encompassing human, environment, and virus genome-wide genetic markers. Immunosuppression, cardiovascular disease, older age, cardiac, gastrointestinal, and constitutional symptoms, rural residence, and specific amino acid substitutions were associated with hospitalization. ICU admission was associated with acute respiratory distress syndrome, ventilation, bacterial co-infection, rural residence, and non-wild type SARS-CoV-2 variants. Finally, long COVID was associated with hospital admission, ventilation, and female sex.Overall, we developed risk assessment models that offer the capability to identify patients with COVID-19 necessitating enhanced monitoring or early interventions. Of importance, we demonstrate the value of including key elements of virus, host, and environmental factors to predict patient outcomes, serving as a valuable platform in the field of personalized medicine with the potential for adaptation to other infectious diseases.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2361791"},"PeriodicalIF":13.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11182058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141199664","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}

{"title":"Deciphering lung granulomas in HIV & TB co-infection: unveiling macrophages aggregation with IL6R/STAT3 activation.","authors":"Qian Li, Cheng Wang, Jizhou Gou, Simo Kitanovski, XiangYi Tang, Yixuan Cai, Chenxia Zhang, Xiling Zhang, Zhenfeng Zhang, Yuanwang Qiu, Fang Zhao, Mengji Lu, Yun He, Jun Wang, Hongzhou Lu","doi":"10.1080/22221751.2024.2366359","DOIUrl":"10.1080/22221751.2024.2366359","url":null,"abstract":"<p><p>Tuberculosis (TB) remains a leading cause of mortality among individuals coinfected with HIV, characterized by progressive pulmonary inflammation. Despite TB's hallmark being focal granulomatous lung lesions, our understanding of the histopathological features and regulation of inflammation in HIV & TB coinfection remains incomplete. In this study, we aimed to elucidate these histopathological features through an immunohistochemistry analysis of HIV & TB co-infected and TB patients, revealing marked differences. Notably, HIV & TB granulomas exhibited aggregation of CD68 + macrophage (Mφ), while TB lesions predominantly featured aggregation of CD20+ B cells, highlighting distinct immune responses in coinfection. Spatial transcriptome profiling further elucidated CD68+ Mφ aggregation in HIV & TB, accompanied by activation of IL6 pathway, potentially exacerbating inflammation. Through multiplex immunostaining, we validated two granuloma types in HIV & TB versus three in TB, distinguished by cell architecture. Remarkably, in the two types of HIV & TB granulomas, CD68 + Mφ highly co-expressed IL6R/pSTAT3, contrasting TB granulomas' high IFNGRA/SOCS3 expression, indicating different signaling pathways at play. Thus, activation of IL6 pathway may intensify inflammation in HIV & TB-lungs, while SOCS3-enriched immune microenvironment suppresses IL6-induced over-inflammation in TB. These findings provide crucial insights into HIV & TB granuloma formation, shedding light on potential therapeutic targets, particularly for granulomatous pulmonary under HIV & TB co-infection. Our study emphasizes the importance of a comprehensive understanding of the immunopathogenesis of HIV & TB coinfection and suggests potential avenues for targeting IL6 signaling with SOCS3 activators or anti-IL6R agents to mitigate lung inflammation in HIV & TB coinfected individuals.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2366359"},"PeriodicalIF":8.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11188963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141295767","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}

{"title":"Disulfide-stabilized trimeric hemagglutinin ectodomains provide enhanced heterologous influenza protection.","authors":"De-Jian Liu, Xiu-Qin Zhong, Yan-Xia Ru, Shi-Long Zhao, Cui-Cui Liu, Yi-Bo Tang, Xuan Wu, Yi-Shuai Zhang, Hui-Hui Zhang, Jia-Yue She, Mu-Yang Wan, Yao-Wang Li, He-Ping Zheng, Lei Deng","doi":"10.1080/22221751.2024.2389095","DOIUrl":"10.1080/22221751.2024.2389095","url":null,"abstract":"<p><p>Influenza virus infection poses a continual menace to public health. Here, we developed soluble trimeric HA ectodomain vaccines by establishing interprotomer disulfide bonds in the stem region, which effectively preserve the native antigenicity of stem epitopes. The stable trimeric H1 ectodomain proteins exhibited higher thermal stabilities in comparison with unmodified HAs and showed strong binding activities towards a panel of anti-stem cross-reactive antibodies that recognize either interprotomer or intraprotomer epitopes. Negative stain transmission electron microscopy (TEM) analysis revealed the stable trimer architecture of the interprotomer disulfide-stapled WA11#5, NC99#2, and FLD#1 proteins as well as the irregular aggregation of unmodified HA molecules. Immunizations of mice with those trimeric HA ectodomain vaccines formulated with incomplete Freund's adjuvant elicited significantly more potent cross-neutralizing antibody responses and offered broader immuno-protection against lethal infections with heterologous influenza strains compared to unmodified HA proteins. Additionally, the findings of our study indicate that elevated levels of HA stem-specific antibody responses correlate with strengthened cross-protections. Our design strategy has proven effective in trimerizing HA ectodomains derived from both influenza A and B viruses, thereby providing a valuable reference for designing future influenza HA immunogens.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2389095"},"PeriodicalIF":8.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11334750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888793","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}

{"title":"Time-resolved scRNA-seq reveals transcription dynamics of polarized macrophages with influenza A virus infection and antigen presentation to T cells.","authors":"Jiapei Yu, Congcong Shang, Xiaoyan Deng, Ju Jia, Xiao Shang, Zeyi Wang, Ying Zheng, Rongling Zhang, Yeming Wang, Hui Zhang, Hongyu Liu, William J Liu, Hui Li, Bin Cao","doi":"10.1080/22221751.2024.2387450","DOIUrl":"10.1080/22221751.2024.2387450","url":null,"abstract":"<p><p>Throughout history, the influenza A virus has caused numerous devastating global pandemics. Macrophages, as pivotal innate immune cells, exhibit a wide range of immune functions characterized by distinct polarization states, reflecting their intricate heterogeneity. In this study, we employed the time-resolved single-cell sequencing technique coupled with metabolic RNA labelling to elucidate the dynamic transcriptional changes in distinct polarized states of bone marrow-derived macrophages (BMDMs) upon infection with the influenza A virus. Our approach not only captures the temporal dimension of transcriptional activity, which is lacking in conventional scRNA-seq methods, but also reveals that M2-polarized <i>Arg1</i>_macrophage cluster is the sole state supporting successful replication of influenza A virus. Furthermore, we identified distinct antigen presentation capabilities to CD4<b>⁺</b> T and CD8<b>⁺</b> T cells across diverse polarized states of macrophages. Notably, the M1 phenotype, exhibited by (BMDMs) and murine alveolar macrophages (AMs), demonstrated superior conventional and cross-presentation abilities for exogenous antigens, with a particular emphasis on cross-presentation capacity. Additionally, as CD8<b>⁺</b> T cell differentiation progressed, M1 polarization exhibited an enhanced capacity for cross-presentation. All three phenotypes of BMDMs, including M1, demonstrated robust presentation to CD4<b>⁺</b> regulatory T cells, while displaying limited ability to present to naive CD4⁺ T cells. These findings offer novel insights into the immunological regulatory mechanisms governing distinct polarized states of macrophages, particularly their roles in restricting the replication of influenza A virus and modulating antigen-specific T cell responses through innate immunity.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2387450"},"PeriodicalIF":8.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11370681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916392","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}

{"title":"Five-year longitudinal surveillance reveals the continual circulation of both alpha- and beta-coronaviruses in Plateau and Gansu pikas (<i>Ochotona</i> spp.) at Qinghai Lake, China¹.","authors":"Lin Xu, Meiqing Song, Xianzhi Tian, Ju Sun, Yanjun Wang, Mengyu Bie, Yuhai Bi, Edward C Holmes, Yi Guan, Jianjun Chen, Juan Li, Weifeng Shi","doi":"10.1080/22221751.2024.2392693","DOIUrl":"10.1080/22221751.2024.2392693","url":null,"abstract":"<p><p>The discovery of alphacoronaviruses and betacoronaviruses in plateau pikas (<i>Ochotona curzoniae</i>) expanded the host range of mammalian coronavirus (CoV) to a new order - Lagomorpha. However, the diversity and evolutionary relationships of CoVs in these plateau-region-specific animal population remains uncertain. We conducted a five-year longitudinal surveillance of CoVs harboured by pikas around Qinghai Lake, China. CoVs were identified in 33 of 236 plateau pikas and 2 of 6 Gansu pikas (<i>Ochotona cansus</i>), with a total positivity rate of 14.5%, and exhibiting a wide spatiotemporal distribution across seven sampling sites and six time points. Through meta-transcriptomic sequencing and RT-PCR, we recovered 16 near-complete viral genome sequences. Phylogenetic analyses classified the viruses as variants of either pika alphacoronaviruses or betacoronaviruses endemic to plateau pikas from the Qinghai-Tibet Plateau region. Of particular note, the pika-associated betacoronaviruses may represent a novel subgenus within the genus <i>Betacoronavirus</i>. Tissue tropism, evaluated using quantitative real-time PCR, revealed the presence of CoV in the rectal and/or lung tissues, with the highest viral loads at 10^3.55 or 10^2.80 RNA copies/μL. Surface plasmon resonance (SPR) assays indicated that the newly identified betacoronavirus did not bind to human or pika Angiotensin-converting enzyme 2 (ACE2) or Dipeptidyl peptidase 4 (DPP4). The findings highlight the ongoing circulation and broadening host spectrum of CoVs among pikas, emphasizing the necessity for further investigation to evaluate their potential public health risks.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2392693"},"PeriodicalIF":8.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11346322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975386","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}