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Targeting Haemaphysalis longicornis serpin to prevent tick feeding and pathogen transmission

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Insect Science 2024年第3期31卷 694-706页

作者： Tingting Feng Hao Tong Qianqian Zhang Zhihao Ming Zhenyu Song Xia Zhou Jianfeng Dai institute of Biology and Medical Sciences Jiangsu Key Laboratory of Infection and ImmunitySoochow UniversitySuzhouJiangsu ProvinceChina School of Biology and Basic Medical Science Suzhou Medical College of Soochow UniversitySuzhouJiangsu ProvinceChina

Serine proteinase inhibitors(serpins),identified from the hard tick Haemaphysalis longicornis of China,play significant roles in various animal physiological *** this study,we showed that *** serpins(Hlserpin-a and Hlserpin-b)were induced during blood-feeding in nymph ticks and exhibited anticoagulation activity in *** Hlserpins through RNA interference(RNAi)significantly impaired tick *** of mice with recombinant Hlserpins or passive transfer of Hlserpin antiserum significantly curtails the efficacy of tick ***,the transmission of the Langat virus(LGTV)from ticks to mice witnessed a substantial decrease when Hlserpins were *** findings suggest that inhibiting Hlserpins can hamper tick engorgement and pathogen transmission,indicating the potential of Hlserpins as a vaccine to countertick-borne diseases.

关键词： feeding LGTV serpin TBEV tick

Immune functions of C-type lectins in medical arthropods

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Insect Science 2024年第3期31卷 652-662页

作者： Zhihao Ming Zhiqiang Chen Hao Tong Xia Zhou Tingting Feng Jianfeng Dai institute of Biology and Medical Sciences Jiangsu Key Laboratory of Infection and ImmunitySoochow UniversitySuzhouJiangsu ProvinceChina School of Biology and Basic Medical Science Suzhou Medical College of Soochow UniversitySuzhouJiangsu ProvinceChina

C-type lectins(CTLs)are a family of proteins that contain 1 or more carbohydrate-recognition domains(CRDs)and bind to a broad repertoire of ligands in the presence of calcium *** play important roles in innate immune defenses against microorganisms by acting as pattern-recognition receptors(PRRs)for invading pathogens,such as bacteria,viruses,and *** binding to pathogen-associated ligands,CTLs mediate immune responses,such as agglutination,phagocytosis,and the activation of phenol oxidase progenitors,thereby clearing *** are an evolutionarily conserved family found in almost all vertebrates and *** arthropods can acquire and transmit a range pathogens through various approaches,such as bloodsucking,lancing,and parasitism,thus infecting humans and animals with related diseases,some of which can be *** studies have shown that lectins are important components of the arthropod immune system and are essential for the immune responses of arthropods to arthropod-borne *** article reviews the current understanding of the structure,function,and signaling pathways involved in CTLs derived from important medical arthropods.

关键词： arthropod C-type lectin innate immunity vector-borne disease

Two hits are better than one:rational dual strategy efficiently fights neuroblastoma

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1802-1804页

作者： Jacques Zimmer Camille Rolin Markus Ollert Department of infection and immunity Luxembourg Institute of HealthEsch-sur-AlzetteLuxembourg University of Luxembourg Esch-sur-AlzetteLuxembourg Department of Dermatology and Allergy Center Odense Research Center for Anaphylaxis(ORCA)University of Southern DenmarkOdenseDenmark

The recently published landmark paper by Bergaggio et *** Roberto Chiarle’s group in Cancer Cell1 investigates an elegant double-hit strategy to improve anti-cancer *** important approach demonstrates in a preclinical model that chimeric antigen receptor(CAR)-T cell treatment can be rendered more efficient by increasing the cell surface expression of the CAR target structure via a small molecule.

关键词： neuroblastoma Cancer

Membrane tension evolution and mechanical regulation of melittin-induced membrane poration

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Chinese Physics B 2024年第10期33卷 465-475页

作者： Wanting Zhang Rong Xu Wendong Ma Zhao Lin Kai Yang Bing Yuan Center for Soft Condensed Matter Physics and Interdisciplinary Research&School of Physical Science and Technology Soochow UniversitySuzhou 215006China Songshan Lake Materials Laboratory Dongguan 523808China Biomedicine Discovery institute Infection&Immunity ProgramMonash UniversityMelbourneAustralia Beijing National Laboratory for Condensed Matter Physics Institute of PhysicsChinese Academy of SciencesBeijing 100190China

Membrane tension plays a crucial role in various fundamental cellular processes,with one notable example being the T cell-mediated elimination of tumor cells through perforin-induced membrane perforation by amplifying cellular ***,the mechanisms governing the regulation of biomolecular activities at the cell interface by membrane tension remain *** this study,we investigated the correlation between membrane tension and poration activity of melittin,a prototypical pore-forming peptide,using dynamic giant unilamellar vesicle leakage assays combined with flickering tension analysis,molecular dynamics simulations,and live cell *** results demonstrate that an increase in membrane tension enhances the activity of melittin,particularly near its critical pore-forming ***,peptide actions such as binding,insertion,and aggregation in the membrane further influence the evolution of membrane *** cell experiments reveal that artificially enhancing membrane tension effectively enhances melittin’s ability to induce pore formation and disrupt membranes,resulting in up to a ten-fold increase in A549 cell mortality when exposed to a concentration of 2.0-μg·mL^(-1)*** findings elucidate the relationship between membrane tension and the mechanism of action as well as pore-forming efficiency of melittin,while providing a practical mechanical approach for regulating functional activity of molecules at the cell-membrane interface.

关键词： membrane tension mechanical regulation membrane poration giant unilamellar vesicle leakage assay

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Major royal-jelly proteins intake modulates immune functions and gut microbiota in mice

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Food Science and Human Wellness 2024年第1期13卷 444-453页

作者： Hang Wu Shican Zhou Wenjuan Ning Xiao Wu Xiaoxiao Xu Zejin Liu Wenhua Liu Kun Liu Lirong Shen Junpeng Wang infection and immunity institute and Translational Medical Center of Huaihe Hospital Henan UniversityKaifeng 475000China College of Biology Science and Engineering Hebei University of Economics and BusinessShijiazhuang 050061China College of Biosystems Engineering and Food Science Zhejiang Key Laboratory for Agro-Food ProcessingZhejiang UniversityHangzhou 310058China

In this study,we investigated the effects of major royal jelly proteins(MRJPs)on the estrogen,gut microbiota,and immunological responses in *** given 250 or 500 mg/kg,not 125 mg/kg of MRJPs,enhanced the proliferation of splenocytes in response to *** splenocytes and mesenteric lymphocytes activated by T-cell mitogens(Con A and anti-CD3/CD28 antibodies)released high levels of IL-2 but low levels of IFN-γand *** release of IL-4 was unaffected by ***,splenocytes and mesenteric lymphocytes activated by LPS were prevented by MRJPs at the same dose as that required for producing IL-1βand IL-6,two pro-inflammatory *** production of IL-1β,IL-6,and IFN-γwas negatively associated with estrogen levels,which were higher in the MRJP-treated animals than in the control *** of the gut microbiota revealed that feeding mice 250 mg/kg of MRJPs maintained the stability of the natural intestinal microflora of ***,the LEf Se analysis identified biomarkers in the MRJP-treated mice,including Prevotella,Bacillales,Enterobacteriales,Gammaproteobacteria,Candidatus_Arthromitus,and *** results showed that MRJPs are important components of royal jelly that modulate host immunity and hormone levels and help maintain gut microbiota stability.

关键词： Major royal-jelly proteins immunity Estrogen Gut microbiota Cytokines

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Superior antibody and membrane protein‑specific T‑cell responses to CoronaVac by intradermal versus intramuscular routes in adolescents

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World Journal of Pediatrics 2024年第4期20卷 353-370页

作者： Jaime S.Rosa Duque Samuel M.S.Cheng Carolyn A.Cohen Daniel Leung Xiwei Wang Xiaofeng Mu Yuet Chung Tsun Ming Lau Manni Wang Wenyue Zhang Yanmei Zhang Howard H.W.Wong Leo C.H.Tsang Sara Chaothai Tsz Chun Kwan John K.C.Li Karl C.K.Chan Leo L.H.Luk Jenson C.H.Ho Wing Yan Li Amos M.T.Lee Jennifer H.Y.Lam Sau Man Chan Wilfred H.S.Wong Issan Y.S.Tam Masashi Mori Sophie A.Valkenburg Malik Peiris Wenwei Tu Yu Lung Lau Department of Paediatrics and Adolescent Medicine The University of Hong KongHong KongChina School of Public Health The University of Hong KongHong KongChina HKU‑Pasteur Research Pole School of Public HealthThe University of Hong KongHong KongChina Research institute for Bioresources and Biotechnology Ishikawa Prefectural UniversityNonoichiJapan Department of Microbiology and Immunology Peter Doherty Institute for Infectionand ImmunityUniversity of MelbourneMelbourneVICAustralia Center for Immunology and infection C2i Hong KongChina

Background Optimising the immunogenicity of COVID-19 vaccines to improve their protection against disease is *** dosing by intradermal(ID)administration has been shown to be equally immunogenic as intramuscular(IM)administration for several vaccines,but the immunogenicity of ID inactivated whole severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)at the full dose is *** study(NCT04800133)investigated the superiority of antibody and T-cell responses of full-dose CoronaVac by ID over IM administration in *** Participants aged 11–17 years received two doses of IM or ID vaccine,followed by the 3rd dose 13–42 days *** and cellular immunogenicity outcomes were measured post-dose 2(IM-CC versus ID-CC)and post-dose 3(IMCCC versus ID-CCC).Doses 2 and 3 were administered to 173 and 104 adolescents,*** Spike protein(S)immunoglobulin G(IgG),S-receptor-binding domain(RBD)IgG,S IgG Fcγreceptor IIIa(FcγRIIIa)-binding,SNM[sum of individual(S),nucleocapsid protein(N),and membrane protein(M)peptide pool]-specific interleukin-2(IL-2)+CD4^(+),SNM-specific IL-2^(+)CD8^(+),S-specific IL-2^(+)CD8^(+),N-specific IL-2^(+)CD4^(+),N-specific IL-2^(+)CD8^(+)and M-specific IL-2^(+)CD4^(+)responses fulfilled the superior and non-inferior criteria for ID-CC compared to IM-CC,whereas IgG avidity was *** ID-CCC,S-RBD IgG,surrogate virus neutralisation test,90%plaque reduction neutralisation titre(PRNT90),PRNT50,S IgG avidity,S IgG FcγRIIIa-binding,M-specific IL-2^(+)CD4^(+),interferon-γ+CD8^(+)and IL-2^(+)CD8^(+)responses were superior and non-inferior to *** estimated vaccine efficacies were 49%,52%,66%and 79%for IM-CC,ID-CC,IM-CCC and ID-CCC,*** ID groups reported more local,mild adverse *** This is the first study to demonstrate superior antibody and M-specific T-cell responses by ID inactivated SARSCoV-2 vaccination and serves as the basis for future research to improve the

关键词： CoronaVac Coronavirus disease 2019 immunity Intradermal Vaccine

Caspase-1 Cleavage of Aldolase B Impairs Hepatic Fructose Metabolism and Aggravates Chronic Viral Hepatitis

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Infectious Microbes & Diseases 2024年第2期6卷 74-84页

作者： Hong Tang Haiming Hu Yanhang Gao Zhilong Wang Feng Yuan Chao Zhang Sisi Deng Pingyun Lyu Jingying Zhan Chengkai Li Hairong Chen Junqi Niu State Key Laboratory for Diagnosis and Treatment of Infectious Diseases The First Affiliated HospitalZhejiang University School of MedicineHangzhouChina Wuhan institute of Virology Chinese Academy of SciencesHubeiChina Department of Hepatology The First Hospital of Jilin UniversityChangchunChina Shanghai institute of immunity and infection Chinese Academy of SciencesShanghaiChina institute of Biophysics Chinese Academy of SciencesBeijingChina

Of dietary monosaccharides,fructose is primarily metabolized by aldolase B(ALDOB)in the liver,whereas glucose is metabolized elsewhere in the *** has been documented that overconsumption of dietary fructose,especially industrial fructose,associates significantly with advanced inflammation in chronic hepatitis C(CHC)***,little is known about whether impaired fructolysis might attribute to CHC *** we found that the level of ALDOB protein was significantly reduced in CHC patients and mice that were persistently infected by hepatitis C virus(HCV).In vitro,HCV infection activated caspase-1,and caspase-3 to a lesser extent,which proteolyzed ALDOB and blocked fructose metabolism in *** of ALDOB attenuated HCV replication,indicating an intrinsic anti-HCV role for homeostatic *** the other hand,reduced ALDOB caused intracellular fructose 1-phosphate accumulation that provoked severe cellular toxicity through intracellular ATP depletion and heightened glycation,which was aggravated by HCV *** together,these results have unveiled that inflammatory activation of caspase-1 impairs homeostatic fructolysis and exacerbates liver damage.

关键词： ALDOB fructose metabolism caspase-1 HCV

mRNA vaccine technology for infectious diseases and beyond

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Science China(Life Sciences) 2024年第10期67卷 2267-2270页

作者： Pei Hao Xiao Li Xuan Li Wu Zhong Key Laboratory of Molecular Virology and Immunology Shanghai Institute of Immunity and InfectionChinese Academy of SciencesShanghai 200031China Changchun Veterinary Research institute Chinese Academy of Agricultural SciencesChangchun 130122China Key Laboratory of Synthetic Biology CAS Center for Excellence in Molecular Plant SciencesInstitute of Plant Physiology and EcologyChinese Academy of SciencesShanghai 200032China National Engineering Research Center for the Emergency Drug Beijing Institute of Pharmacology and ToxicologyBeijing 100085China University of Chinese Academy of Sciences Beijing 100049China

The rise of mRNA vaccine technology Vaccines stand as one of the most significant medical advancements,playing a crucial role in the prevention of infectious diseases and the improvement of global *** triumph of smallpox vaccination stands as a towering achievement in the annals of healthcare,leading to the complete elimination of a oncedevastating disease and showcasing the efficacy of vaccination methods.

关键词： methods vaccination prevention

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Spike N354 glycosylation augments SARS-CoV-2 fitness for human adaptation through structural plasticity

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National Science Review 2024年第7期11卷 80-94页

作者： Pan Liu Can Yue Bo Meng Tianhe Xiao Sijie Yang Shuo Liu Fanchong Jian Qianhui Zhu Yuanling Yu Yanyan Ren Peng Wang Yixin Li Jinyue Wang Xin Mao Fei Shao Youchun Wang Ravindra Kumar Gupta Yunlong Cao Xiangxi Wang CAS Key Laboratory of infection and immunity National Laboratory of MacromoleculesInstitute of BiophysicsChinese Academy of Sciences University of Chinese Academy of Sciences Cambridge institute of Therapeutic Immunology&Infectious Disease(CITIID) University of Cambridge Biomedical Pioneering Innovation Center(BIOPIC) Peking University Changping Laboratory Joint Graduate Program of Peking-Tsinghua-NIBS Academy for Advanced Interdisciplinary Studies Peking University Peking-Tsinghua Center for Life Sciences Tsinghua University Chinese Academy of Medical Sciences&Peking Union Medical College

Selective pressures have given rise to a number of SARS-CoV-2 variants during the prolonged course of the COVID-19 pandemic. Recently evolved variants differ from ancestors in additional glycosylation within the spike protein receptor-binding domain(RBD). Details of how the acquisition of glycosylation impacts viral fitness and human adaptation are not clearly understood. Here, we dissected the role of N354-linked glycosylation, acquired by BA.2.86 sub-lineages, as a RBD conformational control element in attenuating viral infectivity. The reduced infectivity is recovered in the presence of heparin sulfate, which targets the‘N354 pocket’ to ease restrictions of conformational transition resulting in a ‘RBD-up’ state, thereby conferring an adjustable infectivity. Furthermore, N354 glycosylation improved spike cleavage and cell–cell fusion, and in particular escaped one subset of ADCC antibodies. Together with reduced immunogenicity in hybrid immunity background, these indicate a single spike amino acid glycosylation event provides selective advantage in humans through multiple mechanisms.

关键词： coronavirus glycosylation viral fitness adjustable infectivity co-factor usage viral evolution conformational modulator