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  1. Article ; Online: Lys417 acts as a molecular switch that regulates the conformation of SARS-CoV-2 spike protein

    Qibin Geng / Yushun Wan / Fu-Chun Hsueh / Jian Shang / Gang Ye / Fan Bu / Morgan Herbst / Rowan Wilkens / Bin Liu / Fang Li

    eLife, Vol

    2023  Volume 12

    Abstract: SARS-CoV-2 spike protein plays a key role in mediating viral entry and inducing host immune responses. It can adopt either an open or closed conformation based on the position of its receptor-binding domain (RBD). It is yet unclear what causes these ... ...

    Abstract SARS-CoV-2 spike protein plays a key role in mediating viral entry and inducing host immune responses. It can adopt either an open or closed conformation based on the position of its receptor-binding domain (RBD). It is yet unclear what causes these conformational changes or how they influence the spike’s functions. Here, we show that Lys417 in the RBD plays dual roles in the spike’s structure: it stabilizes the closed conformation of the trimeric spike by mediating inter-spike–subunit interactions; it also directly interacts with ACE2 receptor. Hence, a K417V mutation has opposing effects on the spike’s function: it opens up the spike for better ACE2 binding while weakening the RBD’s direct binding to ACE2. The net outcomes of this mutation are to allow the spike to bind ACE2 with higher probability and mediate viral entry more efficiently, but become more exposed to neutralizing antibodies. Given that residue 417 has been a viral mutational hotspot, SARS-CoV-2 may have been evolving to strike a balance between infection potency and immune evasion, contributing to its pandemic spread.
    Keywords SARS-CoV-2 ; spike protein ; viral entry ; immune evasiveness ; receptor-binding domain ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
    Subject code 612
    Language English
    Publishing date 2023-11-01T00:00:00Z
    Publisher eLife Sciences Publications Ltd
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Cryo-EM structure of infectious bronchitis coronavirus spike protein reveals structural and functional evolution of coronavirus spike proteins.

    Jian Shang / Yuan Zheng / Yang Yang / Chang Liu / Qibin Geng / Chuming Luo / Wei Zhang / Fang Li

    PLoS Pathogens, Vol 14, Iss 4, p e

    2018  Volume 1007009

    Abstract: As cell-invading molecular machinery, coronavirus spike proteins pose an evolutionary conundrum due to their high divergence. In this study, we determined the cryo-EM structure of avian infectious bronchitis coronavirus (IBV) spike protein from the γ- ... ...

    Abstract As cell-invading molecular machinery, coronavirus spike proteins pose an evolutionary conundrum due to their high divergence. In this study, we determined the cryo-EM structure of avian infectious bronchitis coronavirus (IBV) spike protein from the γ-genus. The trimeric IBV spike ectodomain contains three receptor-binding S1 heads and a trimeric membrane-fusion S2 stalk. While IBV S2 is structurally similar to those from the other genera, IBV S1 possesses structural features that are unique to different other genera, thereby bridging these diverse spikes into an evolutionary spectrum. Specifically, among different genera, the two domains of S1, the N-terminal domain (S1-NTD) and C-terminal domain (S1-CTD), diverge from simpler tertiary structures and quaternary packing to more complex ones, leading to different functions of the spikes in receptor usage and membrane fusion. Based on the above structural and functional comparisons, we propose that the evolutionary spectrum of coronavirus spikes follows the order of α-, δ-, γ-, and β-genus. This study has provided insight into the evolutionary relationships among coronavirus spikes and deepened our understanding of their structural and functional diversity.
    Keywords Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Subject code 572
    Language English
    Publishing date 2018-04-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Etiology of acute diarrhea in the elderly in China

    Zike Zhang / Shengjie Lai / Jianxing Yu / Qibin Geng / Wanqi Yang / Yu Chen / Jianguo Wu / Huaiqi Jing / Weizhong Yang / Zhongjie Li

    PLoS ONE, Vol 12, Iss 3, p e

    A six-year observational study.

    2017  Volume 0173881

    Abstract: Acute diarrhea leads to a substantial disease burden among the elderly worldwide. However, in the context of increasingly aging trend in China, the prevalence of etiological agents among elderly diarrheal patients was undetermined. This study aimed to ... ...

    Abstract Acute diarrhea leads to a substantial disease burden among the elderly worldwide. However, in the context of increasingly aging trend in China, the prevalence of etiological agents among elderly diarrheal patients was undetermined. This study aimed to explore the major enteropathogens of acute diarrhea among outpatients older than 65 years in China, and also the epidemiological features of the pathogens. Demographic and clinical data for acute diarrhea among outpatients older than 65 years were collected from 213 participating hospitals from 2009 to 2014. Stool specimens were collected and tested for 13 enteric viruses and bacteria. The proportion of outpatients positive for targeted pathogens was analyzed by residential areas and seasonal patterns. Among the 7,725 patients enrolled, 1,617 (20.9%)were positive for any one of the 13 study pathogens. The predominant pathogen was norovirus (9.0%), followed by diarrheagenic Escherichia coli (DEC) (5.5%), rotavirus (3.9%), non-typhoidal Salmonella (NTS) (2.9%), and Shigella spp. (2.5%). The prevalence of Shigella spp. among rural patients (6.9%) was higher than that among urban patients (1.6%) (p < 0.001), with opposite trend for DEC (3.6% versus 5.9%, p = 0.007). An obvious seasonal pattern was observed for major pathogens, with peak for norovirus in autumn, rotavirus in winter and DEC, NTS, and Shigella spp. in summer. A wide variety of enteropathogens were detected among the elderly with acute diarrhea in China, with norovirus and DEC being the most commonly isolated pathogens. A strong seasonal pattern was observed for major pathogens of acute diarrhea among the elderly.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2017-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Novel virus-like nanoparticle vaccine effectively protects animal model from SARS-CoV-2 infection.

    Qibin Geng / Wanbo Tai / Victoria K Baxter / Juan Shi / Yushun Wan / Xiujuan Zhang / Stephanie A Montgomery / Sharon A Taft-Benz / Elizabeth J Anderson / Audrey C Knight / Kenneth H Dinnon / Sarah R Leist / Ralph S Baric / Jian Shang / Sung-Wook Hong / Aleksandra Drelich / Chien-Te K Tseng / Marc Jenkins / Mark Heise /
    Lanying Du / Fang Li

    PLoS Pathogens, Vol 17, Iss 9, p e

    2021  Volume 1009897

    Abstract: The key to battling the COVID-19 pandemic and its potential aftermath is to develop a variety of vaccines that are efficacious and safe, elicit lasting immunity, and cover a range of SARS-CoV-2 variants. Recombinant viral receptor-binding domains (RBDs) ... ...

    Abstract The key to battling the COVID-19 pandemic and its potential aftermath is to develop a variety of vaccines that are efficacious and safe, elicit lasting immunity, and cover a range of SARS-CoV-2 variants. Recombinant viral receptor-binding domains (RBDs) are safe vaccine candidates but often have limited efficacy due to the lack of virus-like immunogen display pattern. Here we have developed a novel virus-like nanoparticle (VLP) vaccine that displays 120 copies of SARS-CoV-2 RBD on its surface. This VLP-RBD vaccine mimics virus-based vaccines in immunogen display, which boosts its efficacy, while maintaining the safety of protein-based subunit vaccines. Compared to the RBD vaccine, the VLP-RBD vaccine induced five times more neutralizing antibodies in mice that efficiently blocked SARS-CoV-2 from attaching to its host receptor and potently neutralized the cell entry of variant SARS-CoV-2 strains, SARS-CoV-1, and SARS-CoV-1-related bat coronavirus. These neutralizing immune responses induced by the VLP-RBD vaccine did not wane during the two-month study period. Furthermore, the VLP-RBD vaccine effectively protected mice from SARS-CoV-2 challenge, dramatically reducing the development of clinical signs and pathological changes in immunized mice. The VLP-RBD vaccine provides one potentially effective solution to controlling the spread of SARS-CoV-2.
    Keywords Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Subject code 570
    Language English
    Publishing date 2021-09-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Incidence of Norovirus-Associated Diarrhea, Shanghai, China, 2012–2013

    Jianxing Yu / Chuchu Ye / Shengjie Lai / Weiping Zhu / Zike Zhang / Qibin Geng / Caoyi Xue / Weizhong Yang / Shuyu Wu / Aron J. Hall / Qiao Sun / Zhongjie Li

    Emerging Infectious Diseases, Vol 23, Iss 2, Pp 312-

    2017  Volume 315

    Abstract: We conducted sentinel-based surveillance for norovirus in the Pudong area of Shanghai, China, during 2012–2013, by analyzing 5,324 community surveys, 408,024 medical records, and 771 laboratory-confirmed norovirus infections among 3,877 diarrhea cases. ... ...

    Abstract We conducted sentinel-based surveillance for norovirus in the Pudong area of Shanghai, China, during 2012–2013, by analyzing 5,324 community surveys, 408,024 medical records, and 771 laboratory-confirmed norovirus infections among 3,877 diarrhea cases. Our analysis indicated an outpatient incidence of 1.5/100 person-years and a community incidence of 8.9/100 person-years for norovirus-associated diarrhea.
    Keywords norovirus ; viruses ; incidence rate ; acute gastroenteritis ; diarrhea ; outpatients ; Medicine ; R ; Infectious and parasitic diseases ; RC109-216
    Language English
    Publishing date 2017-02-01T00:00:00Z
    Publisher Centers for Disease Control and Prevention
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: HRS plays an important role for TLR7 signaling to orchestrate inflammation and innate immunity upon EV71 infection.

    Zhen Luo / Maolin Ge / Junbo Chen / Qibin Geng / Mingfu Tian / Zhi Qiao / Lan Bai / Qi Zhang / Chengliang Zhu / Ying Xiong / Kailang Wu / Fang Liu / Yingle Liu / Jianguo Wu

    PLoS Pathogens, Vol 13, Iss 8, p e

    2017  Volume 1006585

    Abstract: Enterovirus 71 (EV71) is an RNA virus that causes hand-foot-mouth disease (HFMD), and even fatal encephalitis in children. Although EV71 pathogenesis remains largely obscure, host immune responses may play important roles in the development of diseases. ... ...

    Abstract Enterovirus 71 (EV71) is an RNA virus that causes hand-foot-mouth disease (HFMD), and even fatal encephalitis in children. Although EV71 pathogenesis remains largely obscure, host immune responses may play important roles in the development of diseases. Recognition of pathogens mediated by Toll-like receptors (TLRs) induces host immune and inflammatory responses. Intracellular TLRs must traffic from the endoplasmic reticulum (ER) to the endolysosomal network from where they initiate complete signaling, leading to inflammatory response. This study reveals a novel mechanism underlying the regulation of TLR7 signaling during EV71 infection. Initially, we show that multiple cytokines are differentially expressed during viral infection and demonstrate that EV71 infection induces the production of proinflammatory cytokines through regulating TLR7-mediated p38 MAPK, and NF-κB signaling pathways. Further studies reveal that the expression of the endosome-associated protein hepatocyte growth factor-regulated tyrosine kinase substrate (HRS) is upregulated and highly correlated with the expression of TLR7 in EV71 infected patients, mice, and cultured cells. Virus-induced HRS subsequently enhances TLR7 complex formation in early- and late-endosome by interacting with TLR7 and TAB1. Moreover, HRS is involved in the regulation of the TLR7/NF-κB/p38 MAPK and the TLR7/NF-κB/IRF3 signaling pathways to induce proinflammatory cytokines and interferons, respectively, resulting in the orchestration of inflammatory and immune responses to the EV71 infection. Therefore, this study demonstrates that HRS acts as a key component of TLR7 signaling to orchestrate immune and inflammatory responses during EV71 infection, and provides new insights into the mechanisms underlying the regulation of host inflammation and innate immunity during EV71 infection.
    Keywords Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Subject code 570
    Language English
    Publishing date 2017-08-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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