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Efficient antibody evasion but reduced ACE2 binding by the emerging SARS-CoV-2 variant B.1.640.2

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Cellular & Molecular Immunology 2022年第9期19卷 1067-1069页

作者： Prerna Arora Amy Kempf Inga Nehlmeier Luise Graichen Sebastian Schulz Anne Cossmann Alexandra Dopfer-jablonka martin S.Winkler hans-martin jäck Georg M.N.Behrens Stefan Pöhlmann Markus Hoffmann Infection Biology Unit German Primate CenterKellnerweg 437077GöttingenGermany Faculty of Biology and Psychology Georg-August-University GöttingenWilhelmsplatz 137073GöttingenGermany Division of Molecular Immunology Department of Internal Medicine 3Friedrich-Alexander University of Erlangen-NürnbergGlückstraße 691054ErlangenGermany Department for Rheumatology and Immunology Hannover Medical SchoolCarl-Neuberg-Straße 130625HannoverGermany German Centre for Infection Research(DZIF) Partner Site Hannover-BraunschweigHannoverGermany Centre for Individualised Infection Medicine(CiiM) HannoverGermany Department of Anesthesiology University of Göttingen Medical CenterGöttingenGeorg-August University of GöttingenRobert-Koch-Straße 4037075GöttingenGermany

The SARS-CoV-2 spike(S)protein engages ACE2 for cell entry,and the S protein/ACE2 interface is an important target for neutralizing antibodies.In the course of the COVID-19 pandemic,SARS-CoV-2 variants have emerged that harbor mutations in the S protein,which confer neutralization resistance and allow viral spread in immunologically nonnaive populations.The most prominent example is the highly mutated Omicron variant,which infects convalescent or vaccinated individuals with unprecedented efficiency[1,2].

关键词： ACE2 harbor neutral

Profound neutralization evasion and augmented host cell entry are hallmarks of the fast-spreading SARS-CoV-2 lineage XBB.1.5

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Cellular & Molecular Immunology 2023年第4期20卷 419-422页

作者： Markus Hoffmann Prerna Arora Inga Nehlmeier Amy Kempf Anne Cossmann Sebastian R.Schulz Gema Morillas Ramos Luis A.Manthey hans-martin jäck Georg M.N.Behrens Stefan Pöhlmann Infection Biology Unit German Primate CenterKellnerweg 437077 GöttingenGermany Faculty of Biology and Psychology Georg-August-University GöttingenWilhelmsplatz 137073 GöttingenGermany Department for Rheumatology and Immunology Hannover Medical SchoolCarl-Neuberg-Straße 130625 HannoverGermany Division of Molecular Immunology Department of Internal Medicine 3Friedrich-Alexander University of Erlangen-NürnbergGlückstraße 691054 ErlangenGermany German Centre for Infection Research(DZIF) partner site Hannover-BraunschweigCarl-Neuberg-Straße 130625 HannoverGermany Centre for Individualized Infection Medicine(CiiM) FeodorLynen-Straße730625 HannoverGermany

Since late 2022, the share of infections caused by the SARS-CoV2 lineage XBB.1.5 has gradually increased in the United States,resulting in XBB.1.5 becoming the dominating SARS-CoV-2lineage in the United States and a similar trend is likely to soontake place also in European countries. However, information onthe virological properties of XBB.1.5 is scarce. Here, weconducted an initial virological assessment of the SARS-CoV-2XBB.1.5 lineage.

关键词： becoming likely lineage

Host cell entry and neutralisation sensitivity of the SARS-CoV-2 XBB.1.16 lineage

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Cellular & Molecular Immunology 2023年第8期20卷 969-971页

作者： Inga Nehlmeier Amy Kempf Prerna Arora Anne Cossmann Alexandra Dopfer-jablonka Metodi V.Stankov Sebastian R.Schulz hans-martin jäck Georg M.N.Behrens Stefan Pöhlmann Markus Hoffmann Infection Biology Unit German Primate Center—Leibniz Institute for Primate ResearchKellnerweg 437077GöttingenGermany Faculty of Biology and Psychology Georg-August-University GöttingenWilhelmsplatz 137073GöttingenGermany Department of Rheumatology and Immunology Hannover Medical SchoolCarl-Neuberg-Straße 130625HannoverGermany German Centre for Infection Research(DZIF) Partner Site Hannover-BraunschweigCarl-Neuberg-Straße 130625HannoverGermany Division of Molecular Immunology Department of Internal Medicine 3Friedrich-Alexander University of Erlangen-NürnbergGlückstraße 691054ErlangenGermany Centre for Individualized Infection Medicine(CiiM) Feodor-Lynen-Straße 730625HannoverGermany

Despite previous circulation of the highly transmissible and antibody evasive BA.2.75, BQ.1, XBB.1 and XBB.1.5 lineages, the share of infections caused by the SARS-CoV-2 lineage XBB.1.16 has gradually increased in India in early 2023, resulting in XBB.1.16 being the dominating SARS-CoV-2 lineage in India today. Since a similar trend may also take place in other countries and information on the biological properties of the XBB.1.16 lineage is scarce, we conducted a rapid assessment of the SARS-CoV-2 XBB.1.16 lineage with respect to its ability to enter cells and evade neutralisation by antibodies.

关键词： lineage neutral spite

The spike protein of SARS-CoV-2 variant A.30 is heavily mutated and evades vaccine-induced antibodies with high efficiency

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Cellular & Molecular Immunology 2021年第12期18卷 2673-2675页

作者： Prerna Arora Cheila Rocha Amy Kempf Inga Nehlmeier Luise Graichen martin S.Winkler martin Lier Sebastian Schulz hans-martin jäck Anne Cossmann Metodi V.Stankov Georg M.N.Behrens Stefan Pöhlmann Markus Hoffmann Infection Biology Unit German Primate CenterKellnerweg 437077GöttingenGermany Faculty of Biology and Psychology Georg-August-University GöttingenWilhelmsplatz 137073GöttingenGermany Department of Anesthesiology University of Göttingen Medical CenterGeorg-August University of GöttingenRobert-Koch-Straße 4037075GöttingenGermany Division of Molecular Immunology Department of Internal Medicine 3Friedrich-Alexander University of Erlangen-NürnbergGlückstraße 691054ErlangenGermany Department for Rheumatology and Immunology Hannover Medical SchoolCarl-Neuberg-Straße 130625HannoverGermany

The COVID-19 pandemic,caused by SARS-CoV-2,continues to rage in many countries,straining health systems and economies.Vaccines protect against severe disease and death and are considered central to ending the pandemic.COVID-19 vaccines(and SARS-CoV-2 infection)elicit antibodies that are directed against the viral spike(S)protein and neutralize the virus.However,the emergence of SARS-CoV-2 variants with S protein mutations that confer resistance to neutralization might compromise vaccine efficacy[1].

关键词： antibodies vaccine death

Delta variant(B.1.617.2)sublineages do not show increased neutralization resistance

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Cellular & Molecular Immunology 2021年第11期18卷 2557-2559页

作者： Prerna Arora Amy Kempf Inga Nehlmeier Luise Graichen Anzhalika Sidarovich martin S.Winkler Sebastian Schulz hans-martin jäck Metodi V.Stankov Georg M.N.Behrens Stefan Pöhlmann Markus Hoffmann Infection Biology Unit German Primate CenterGöttingenGermany Faculty of Biology and Psychology Georg-August-University GöttingenGöttingenGermany Department of Anesthesiology University of Göttingen Medical CenterGeorg-August University GöttingenGöttingenGermany Division of Molecular Immunology Department of Internal Medicine 3Friedrich-Alexander University of Erlangen-NürnbergErlangenGermany Department for Rheumatology and Immunology Hannover Medical SchoolHannoverGermany

The emergence of SARS-CoV-2 variants threatens efforts to control the COVID-19 pandemic.At present,the global spread of the Delta(B.1.617.2)variant is responsible for a rapid increase in COVID-19 cases and hospitalizations in many countries.The variant evades neutralizing antibodies and is believed to be more transmissible and pathogenic[1,2,3,4].

关键词： Delta neutral resistance

Endothelial dysfunction contributes to severe COVID-19 in combination with dysregulated lymphocyte responses and cytokine networks

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Signal Transduction and Targeted Therapy 2022年第1期7卷 243-257页

作者： Louisa Ruhl Isabell Pink jenny F.Kiihne Kerstin Beushausen jana Keil Stella Christoph Andrea Sauer Lennart Boblitz julius Schmidt Sascha David hans-martin jack Edith Roth Markus Cornberg Thomas F.Schulz Tobias Welte Marius M.Hoper Christine S.Falk Institute of Transplant Immunology MHHDHanoverGermany Department of Pneumology MHHDHanoverGermany Department of Intensive Care Medicine University of ZurichCHZurichSwitzerland Division of Molecular Immunology Internal Medicine IIINikolaus-Fiebiger-Center of Molecular MedicineFriedrich-Alexander University Erlangen-NurnbergDErlangenGermany Department of Gastroenterology Hepatology and Endocrinology MHHDHanoverGermany Center for Individualized Infection Medicine CiiM HanoverGermany lnstitute of Virology MHHDHanoverGermany German Center for Infection Research DZIFTTU-IICHMarburgGermany Excellence Cluster 2155 RESIST MHHHanoverGermany German Center for Lung Diseases DZL/BREATH MarburgGermany

The systemic processes involved in the manifestation of life・threatening COVID-19 and in disease recovery are still incompletely understood,despite investigations focusing on the dysregulation of immune responses after SARS-CoV-2 infection.To define hallmarks of severe COVID-19 in acute disease(n=58)and in disease recovery in con valesce nt patie nts(n=28)from Han nover Medical School,we used flow cytometry and proteomics data with unsupervised clustering analyses.In our observational study,we combined analyses of immune cells and cytokine/chemokine networks with endothelial activation and injury.ICU patients displayed an altered immune signature with prolonged lymphopenia but the expansion of granulocytes and plasmablasts along with activated and terminally differentiated T and NK cells and high levels of SARS-CoV-2-specific antibodies.The core signature of seven plasma proteins revealed a highly inflammatory microenvironment in addition to endothelial injury in severe COVID-19.Changes within this sign ature were associated with either disease progression or recovery.In summary,our data suggest that besides a strong inflammatory response,severe COVID-19 is driven by endothelial activation and barrier disruption,whereby recovery depends on the regeneration of the endothelial integrity.

关键词： cytokine networks signature

Alternative polyadenylation events in epithelial cells sense endometritis progression in dairy cows

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journal of Integrative Agriculture 2023年第6期22卷 1820-1832页

作者： Meagan j.STOTTS Yangzi ZHANG Shuwen ZHANG jennifer j.MICHAL juan VELEZ Bothe hans martin MAQUIVAR Zhihua jIANG Department of Animal Sciences and Center for Reproductive Biology Washington State UniversityPullmanWA 99164-7620USA Aurora Organic Farms PlattevilleCO 80651USA

Endometritis(inflammation of the endometrial lining) is one of the most devastating reproductive diseases in dairy cattle, resulting in substantial production loss and causing more than $650 million in lost revenue annually in the USA.We hypothesize that alternative polyadenylation(APA) sites serve as decisive sensors for endometrium health and disease in dairy cows. Endometrial cells collected from 18 cows with purulent vaginal discharge scored 0 to 2 were used for APA profiling with our whole transcriptome termini site sequencing(WTTS-seq) method. Overall, pathogens trigger hosts to use more differentially expressed APA(DE-APA), more intronic DE-APA, more DE-APA sites per gene and more DE-genes associated with inflammation. Host CD59 molecule(CD59), Fc fragment of IgG receptor IIa(FCGR2A), lymphocyte antigen 75(LY75) and plasminogen(PLG) may serve as initial contacts or combats with pathogens on cell surface, followed by activation of nuclear receptor subfamily 1 group H member 4(NR1H4) to regulate AXL receptor tyrosine kinase(AXL), FGR proto-oncogene, Src family tyrosine kinase(FGR), Hck protooncogene, Src family tyrosine kinase(Hck) and integrin subunit beta 2(ITGB2) for anti-inflammation. This study is the first to show significance of cilium pathways in endometrium health and animal reproduction. MIR21 and MIR30A would be perfect antagonistic biomarkers for diagnosis of either inflammation or anti-inflammation. These novel findings will set precedent for future genomic studies to aid the dairy industry develop new strategies to reduce endometritis incidence and improve fertility.

关键词： organic dairy endometritis alternative polyadenylation infection progression antagonistic biomarkers

Split liver transplantation: Current developments

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World journal of Gastroenterology 2018年第47期24卷 5312-5321页

作者： Christina Hackl Katharina M Schmidt Caner Süsal Bernd Dohler martin Zidek hans j Schlitt Department of Surgery University Hospital RegensburgRegensburg 93053Germany Collaborative Transplant Study (CTS) Institute of ImmunologyHeidelberg UniversityHeidelberg 69120Germany

In 1988, Rudolf Pichlmayr pioneered split liver transplantation(SLT), enabling the transplantation of one donor liver into two recipients-one pediatric and one adult patient. In the same year, Henri Bismuth and colleagues performed the first full right/full left split procedure with two adult recipients. Both splitting techniques were rapidly adopted within the transplant community. However, a SLT is technically demanding, may cause increased perioperative complications, and may potentially transform an excellent deceased donor organ into two marginal quality grafts. Thus, crucial evaluation of donor organs suitable for splitting and careful screening of potential SLT recipients is warranted. Furthermore, the logistic background of the splitting procedure as well as the organ allocation policy must be adapted to further increase the number and the safety of SLT. Under defined circumstances, in selected patients and at experienced transplant centers, SLT outcomes can be similar to those obtained in full organ LT. Thus, SLT is an important tool to reduce the donor organ shortage and waitlist mortality, especially for pediatric patients and small adults. The present review gives an overview of technical aspects, current developments, and clinical outcomes of SLT.

关键词： Liver transplantation organ shortage in situ split extended right lobe left lateral lobe living donor

Interaction of the α2A domain of integrin with small collagen fragments

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Protein & Cell 2010年第4期1卷 393-405页

作者： hans-Christian Siebert Monika Burg-Roderfeld Thomas Eckert Sabine Stötzel Ulrike Kirch Tammo Diercks martin j.Humphries martin Frank Rainer Wechselberger Emad Tajkhorshid Steffen Oesser Institut für Biochemie und Endokrinologie Veterinärmedizinische FakultätJustus-Liebig-Universität GießenFrankfurter Str.10035392 GießenGermany CiC bioGUNE Parque Tecnológico de BizkaiaEdificio 80048160 DerioSpain Utrecht Facility for High-resolution NMR Bijvoetcenter for Biomolecular Research Utrecht UniversityPadualaan 83584CH UtrechtThe Netherlands Wellcome Trust Centre for Cell-Matrix Research School of Biological SciencesUniversity of Manchester2.205 Stopford BuildingOxford RoadManchester M139PTUK Molecular Structure Analysis Core Facility Deutsches KrebsforschungszentrumIm Neuenheimer Feld 28069120 HeidelbergGermany Department of Biochemistry Beckman Instituteand Center for Biophysics and Computational BiologyUniversity of Illinois at Urbana-ChampaignUrbanaILUSA Collagen Research Institute Schauenburgerstr.116D-24118 KielGermany

We here present a detailed study of the ligand-receptor interactions between single and triple-helical strands of collagen and the α2A domain of integrin(α2A),providing valuable new insights into the mechanisms and dynamics of collagen-integrin binding at a sub-molecular level.The occurrence of single and triple-helical strands of the collagen fragments was scrutinized with atom force microscopy(AFM)techniques.Strong interactions of the triple-stranded fragments comparable to those of collagen can only be detected for the 42mer triple-helical collagen-like peptide under study(which contains 42 amino acid residues per strand)by solid phase assays as well as by surface plasmon resonance(SPR)measurements.However,changes in NMR signals during titration and characteristic saturation transfer difference(STD)NMR signals are also detectable whenα2A is added to a solution of the 21mer single-stranded collagen fragment.Molecular dynamics(MD)simulations employing different sets of force field parameters were applied to study the interaction between triple-helical or single-stranded collagen fragments withα2A.It is remarkable that even single-stranded collagen fragments can form various complexes withα2A showing significant differences in the complex stability with identical ligands.The results of MD simulations are in agreement with the signal alterations in our NMR experiments,which are indicative of the formation of weak complexes between single-stranded collagen andα2A in solution.These results provide useful information concerning possible interactions ofα2A with small collagen fragments that are of relevance to the design of novel therapeutic A-domain inhibitors.

关键词： integrin-collagen interaction NMR SPR AFM molecular modeling