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Unusual outcome of in utero infection and subsequent postnatal super-infection with different PCV2b strains

Virologica Sinica 2014年第3期29卷 176-182页

作者： Dipongkor Saha Uladzimir U.Karniychuk Liping Huang Marc Geldhof Merijn Vanhee David J.Lefebvre Peter Meerts Richard Ducatelle Jan V.Doorsselaere Hans J.Nauwynck laboratory of Virology Department of Virology Parasitology and Immunology Faculty of Veterinary Medicine Ghent UniversityBelgium Brain tumor Research Center Department of Molecular Neurosurgery Harvard Medical School and Massachusetts General Hospital 185 Cambridge StreetBoston MA-02114 USA Division of Experimental Therapeutics Toronto General Hospital Research Institute University Health NetworkToronto Canada Division of Swine Infectious Diseases Harbin Veterinary Research Institute The Chinese Academy of Agricultural Sciences Department of Health Care and Biotechnology KATHO Catholic University College of South-West FlandersBelgium CODA-CERVA Groeselenberg 99 1180 Ukkel Belgium Ablynx nv Technologiepark 219052 Zwijnaarde Belgium Department of Pathology Bacteriology and Poultry Diseases Faculty of Veterinary Medicine Ghent UniversityBelgium

VC2002, isolated from postweaning multisystemic wasting syndrome(PMWS)-affected pig, is a mixture of two porcine circovirus genotype 2b(PCV2b) viruses, K2 and K39. Preliminary experiments disclosed short-term adverse effects of K39, but not K2, on porcine foetuses. These findings led to the hypothesis that infection of immuno-incompetent foetuses with K2 confers a status of immunotolerance, and postnatal super-infection with K39 triggers PMWS. To explore this hypothesis, nine 55-day-old foetuses were inoculated in utero(three with K2-104.3TCID50, three with K39-104.3TCID50 and three with medium), and foeto-pathogenicity examined. At 21 days post-inoculation(dpi), K2 did not induce pathology, whereas pathological effects of K39 were evident. Twenty-four 45-day-old foetuses were subsequently inoculated to examine the long-term effect of K2, including six with K2-high dose-104.3TCID50, six with K2-low dose-102.3TCID50 and 12 mock-inoculated controls. Both doses resulted in five mummified foetuses and one live-born piglet each(69dpi). K2 was recovered from all mummies. K2 and K2-specific antibodies were not detected in serum of the two live-born piglets at birth, indicating full control of K2 infection. The K2-low dose-infected piglet was immunostimulated at day 2, but not the K2-high dose-infected piglet. Both non-stimulated and stimulated K2-infected piglets were super-inoculated with K39 at day 6 or 8(taken as 0 days post super-inoculation). Low viral replication was observed in the non-stimulated K2-K39 piglet(up to 103.3 TCID50/g; identified as K39). In contrast, viral replication was extremely high in the stimulated K2-K39 piglet(up to 105.6TCID50/g) and identified as K2, indicating that K2 infection is controlled during foetal life, but emerges after birth upon immunostimulation. However, none of the piglets showed any signs of PMWS.

关键词：感染生后断奶后多系统衰竭综合征猪圆环病毒品系 PMWS 免疫耐受病毒复制

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Gp350-anchored extracellular vesicles: promising vehicles for delivering therapeutic drugs of B cell malignancies

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Asian Journal of Pharmaceutical Sciences 2022年第3期17卷 462-474页

作者： Huiqing Xiu Xi Nan Danfeng Guo JiaoliWang Jiahui Li Yanmei Peng Guirun Xiong Shibo Wang Changjun Wang Gensheng Zhang Yunshan Yang Zhijian Cai Institute of Immunology and Department of Orthopedics of the Second Affiliated HospitalZhejiang University School of MedicineHangzhouChina Henan Key laboratory for Digestive Organ Transplantation the First Affiliated Hospital of Zhengzhou UniversityZhengzhouChina Key laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province Affiliated Hangzhou First People’s HospitalZhejiang University School of MedicineHangzhouChina Zhejiang University Cancer Centre HangzhouChina Department of Critical Care Medicine of the Second Affiliated Hospital Zhejiang University School of MedicineHangzhouChina Department of Emergency Medicine Tongde Hospital of Zhejiang ProvinceHangzhouChina Second Affiliated Hospital of Zhejiang University School of Medicine Zhejiang Provincial Key Lab of OphthalmologyHangzhouChina Department of Medical Oncology The Cancer Hospital of the University of Chinese Academy of Sciences(Zhejiang Cancer Hospital)Institute of Basic Medicine and Cancer(IBMC)Chinese Academy of SciencesHangzhouChina

Although chimeric antigen receptor-modified(CAR)T cell therapy has been successfully applied in the treatment of acute B lymphocytic leukemia,its effect on Burkitt lymphoma(BL)and chronic B lymphocytic leukemia(B-CLL)is ***,fatal side effects greatly impede CAR T cell *** vesicles(EVs)are excellent carriers of therapeutic ***,EVs mainly accumulate in the liver when administered without *** an envelope glycoprotein of Epstein–Barr viruses,gp350 can efficiently bind CD21 on B ***,gp350 was directly anchored onto red blood cell EVs(RBC-EVs)via its transmembrane region combined with low-voltage *** results showed that gp350 could anchor to RBC-EVs with high efficiency and that the resulting gp350-anchored RBC-EVs(RBC-EVs/gp350^(Etp))exhibited increased targeting to CD21+BL and B-CLL relative to *** the loading of doxorubicin or fludarabine,RBC-EVs/gp350^(Etp) had powerful cytotoxicity and therapeutic efficacy on CD21+BL or B-CLL,***,RBC-EVs/gp350^(Etp) loaded with a drug did not exhibit any apparent systemic toxicity and specifically induced the apoptosis of tumor B cells but not normal ***,our findings indicate that drug-loaded RBC-EVs/gp350^(Etp) may be adopted in the treatment of CD21+B cell malignancies.

关键词： Extracellular vesicles Gp350 CD21 Red blood cells B cell malignancies

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Fish TNF and TNF receptors

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Science China(Life Sciences) 2021年第2期64卷 196-220页

作者： Yaoguo Li Tiaoyi Xiao Jun Zou Hunan Engineering Technology Research Center of Featured Aquatic Resources Utilization Hunan Agricultural UniversityChangsha 410128China Key laboratory of Exploration and Utilization of Aquatic Genetic Resources Ministry of EducationShanghai Ocean UniversityShanghai 201306China International Research Center for Marine Biosciences at Shanghai Ocean University Ministry of Science and TechnologyShanghai 201306China Alaboratory for Marine Biology and Biotechnology Qingdao National Laboratory for Marine Science and TechnologyQingdao 266237China

tumor necrosis factors(TNFs)are a group of cytokines that play critical roles in regulating a diverse range of physiological processes in *** function by activating a large number of structurally related receptors,leading to TNF mediated biological processes which are evolutionarily *** have a much diversified TNF family,partly due to the whole genome duplication events which have occurred in this lineage,providing an excellent model to investigate the neo-and subfunctionalised properties of TNF *** possess most of the TNFs and receptors found in mammals and also some homologues exclusively present in *** seems that TNFSF4(OX40),TNFSF7(CD27)and TNFSF8(CD30)and their cognate receptors are absent in *** has been shown that fish viruses are able to produce TNFR homologues to establish infection by manipulating the host immune *** the roles of TNFSFs in fish immune defence and the pathogenesis of fish diseases will provide insights into the functions of TNFSFs from an evolutionary perspective and better strategies for improving fish health and welfare in *** review summarises recent advances in the study of fish TNF biology and focuses on the molecular properties and immunological functions of the TNF and TNFR superfamily.

关键词： tumor necrosis factor superfamily TNF receptor cytokine evolution fish

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Advance in the use of gold nanoparticles in the treatment of neurodegenerative diseases:new perspectives

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Neural Regeneration Research 2021年第12期16卷 2425-2426页

作者： Gustavo de Bem Silveira Alexandre Pastoris Muller Ricardo Andrez Machado-de-Ávila Paulo Cesar Lock Silveira laboratory of Experimental Pathophysiology Graduate Program in Health SciencesUniversidade do Extremo Sul CatarinenseCriciúmaSCBrazil Programa de Pós Graduação em Farmacologia UFSCFlorianópolisSCBrazil

Various conditions affecting nerve cells and the nervous system due to the loss of neurons and their connecting networks are described under the superordinate phrase“Neurodegenerative diseases”.Such diseases lead to disability due to gradual neuronal death in both the central nervous system and the peripheral nervous *** many of these diseases have unknown causes,sometimes these are due to medical conditions such as alcoholism,a tumor,or a stroke,or other causes which may include genetic mutations,toxins,chemicals,and viruses.

关键词： diseases degenerative treatment

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Signaling pathways in the regulation of cytokine release syndrome in human diseases and intervention therapy

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Signal Transduction and Targeted Therapy 2021年第11期6卷 3230-3245页

作者： Xia Li Mi Shao Xiangjun Zeng Pengxu Qian He Huang Bone Marrow Transplantation Center The First Affiliated HospitalZhejiang University School of MedicineHangzhouPeople’s Republic of China Liangzhu laboratory Zhejiang University Medical Center1369 West Wenyi RoadHangzhou311121People’s Republic of China Institute of Hematology Zhejiang UniversityHangzhouZhejiangPeople’s Republic of China Zhejiang Province Engineering laboratory for Stem Cell and Immunity Therapy HangzhouZhejiangPeople’s Republic of China Center of Stem Cell and Regenerative Medicine Zhejiang University School of MedicineHangzhouPeople’s Republic of China

Cytokine release syndrome(CRS)embodies a mixture of clinical manifestations,including elevated circulating cytokine levels,acute systemic inflammatory symptoms and secondary organ dysfunction,which was first described in the context of acute graft-versus-host disease after allogeneic hematopoietic stem-cell transplantation and was later observed in pandemics of influenza,SARS-CoV and COVID-19,immunotherapy of tumor,after chimeric antigen receptor T(CAR-T)therapy,and in monogenic disorders and autoimmune ***,severe CRS is a very significant and life-threatening complication,which is clinically characterized by persistent high fever,hyperinflammation,and severe organ ***,CRS is a double-edged sword,which may be both helpful in controlling tumors/viruses/infections and harmful to the *** a high incidence and high levels of cytokines are features of CRS,the detailed kinetics and specific mechanisms of CRS in human diseases and intervention therapy remain *** the present review,we have summarized the most recent advances related to the clinical features and management of CRS as well as cutting-edge technologies to elucidate the mechanisms of *** that CRS is the major adverse event in human diseases and intervention therapy,our review delineates the characteristics,kinetics,signaling pathways,and potential mechanisms of CRS,which shows its clinical relevance for achieving both favorable efficacy and low toxicity.

关键词： cytokine release kinetics

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Oncoselectivity in Oncolytic viruses against Colorectal Cancer

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Journal of Cancer Therapy 2014年第13期5卷 1153-1174页

作者： Steven J. Conrad Karim Essani laboratory of Virology Department of Biological Sciences Western Michigan University Kalamazoo USA

In humans colorectal cancer (CRC) is a significant cause of morbidity and mortality. New treatment options are urgently needed to supplement existing therapies. Replication-competent oncolytic viruses (RCOVs) for the treatment of cancerous tumors?in vivo?is a relatively new therapeutic modality with great but largely unrealized potential against CRC. In the context of oncolytic virus safety, oncoselectivity is an important criterion. It is at the conceptual intersection of viral replication strategy and tumor cell biology that RCOVs acquire their oncoselectivity, and thus their safety. Every aspect of tumor molecular biology which distinguishes it from normal, non-neoplastic cells is a potential target for exploitation. In the first section of this review we will provide an explanation of some of the successful and widely used strategies for improving oncoselectivity in wild-type viruses to make them more suitable as RCOVs. In the second section we will describe some of the characteristics of CRC biology which can be exploited to provide oncoselectivity against CRC. Throughout the review examples of successfully-engineered RCOVs which embody the approach or strategy under discussion are noted. By showing what has been done, we hope to highlight what is possible and what remains to be done to generate oncoselective RCOVs for use against CRC in humans.

关键词： Colorectal Cancer Replication-Competent Oncolytic Virus Oncoselectivity Virotherapy

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HBV Integration Induces Complex Interactions between Host and Viral Genomic Functions at the Insertion Site

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Journal of Clinical and Translational Hepatology 2021年第3期9卷 399-408页

作者： Dake Zhang Ke Zhang Urlike Protzer Changqing Zeng Beijing Advanced Innovation Centre for Biomedical Engineering Key Laboratory for Biomechanics and Mechanobiology of Ministry of EducationSchool of Biological Science and Medical EngineeringBeihang UniversityBeijingChina SCG Cell Therapy Pte.Ltd Singapore Institute of Virology Technical University of Munich/Helmholtz Zentrum MünchenMunichGermany German Center for Infection Research(DZIF) MunichGermany Key laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of SciencesBeijingChina University of Chinese Academy of Sciences BeijingChina

Hepatitis B virus(HBV),one of the well-known DNA oncogenic viruses,is the leading cause of hepatocellular carcinoma(HCC).In infected hepatocytes,HBV DNA can be integrated into the host genome through an insertional mutagenesis process inducing *** of the genomic features surrounding integration sites will deepen our understanding of mechanisms underlying ***,the quantity and biological activity of integration sites may reflect the DNA damage within affected cells or the potential survival benefits they may *** wellknown human genomic features include repeat elements,particular regions(such as telomeres),and frequently interrupted genes(e.g.,telomerase reverse transcriptase[***],lysine methyltransferase 2B[***2B],cyclin E1[CCNE1],and cyclin A2[CCNA2]).Consequently,distinct genomic features within diverse integrations differentiate their biological ***,accumulating evidence has shown that viral proteins produced by integrants may cause cell damage even after the suppression of HBV *** integration-derived gene products can also serve as tumor markers,promoting the development of novel therapeutic strategies for *** integrants can be single copy or multiple copies of different fragments with complicated rearrangement,which warrants elucidation of the whole viral integrant arrangement in future *** of these considerations underlie an urgent need to develop novel methodology and technology for sequence characterization and function evaluation of integration events in chronic hepatitis B-associated disease progression by monitoring both host genomic features and viral *** endeavor may also serve as a promising solution for evaluating the risk of tumorigenesis and as a companion diagnostic for designing therapeutic strategies targeting integration-related disease complications.

关键词： Double-strand break Chimeric reads Junction reads Fusion transcript Virus cellular junction Virus cell junction Virus host junction

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Recent advances regarding tumor microenvironment and immunotherapy in hepatocellular carcinoma

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Hepatoma Research 2020年第5期6卷 43-60页

作者： Wei Qin Zhen-Yu Cao Si-Yuan Liu Xun-Di Xu Hunan Provincial Key laboratory of Hepatobiliary Disease Research Division of Hepatobiliary&Pancreatic SurgeryDepartment of SurgeryThe Second Xiangya HospitalCentral South UniversityChangsha 410011HunanChina

Hepatocellular carcinoma(HCC)is one of the most common malignant tumors of the liver,with poor prognosis and high *** treatments for patients with HCC have shown poor efficacy especially for advanced liver *** with other organs,the liver has more natural immune cells such as Kupffer cells,natural killer cells and natural killer T *** for liver cancer has become the focus in current *** theoretical basis of immunotherapy rests on immune tolerance and suppression in the tumor *** immunotherapy methods include vaccines,cytokines,adoptive cell therapies,immune checkpoint inhibitors,and oncolytic *** with traditional treatment,immunotherapy can enhance the body’s immune function,delay tumor progression,and prolong *** article reviews the HCC microenvironment and immunotherapy both in the clinical and basic research aspects.

关键词： Immunotherapy hepatocellular carcinoma microenvironment immune

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Programming CAR T cells to enhance anti-tumor efficacy through remodeling of the immune system

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Frontiers of Medicine 2020年第6期14卷 726-745页

作者： Xiaohui Wang Zhiqiang Wu Wei Qiu Ping Chen Xiang Xu Weidong Han College of Biotechnology Southwest UniversityChongqing 400715China State Key laboratory of Trauma Burn and Combined InjuryDepartment of Stem Cell&Regenerative MedicineDaping Hospital and Research Institute of SurgeryChongqing 400042China Molecular&Immunological Department Bio-therapeutic DepartmentChinese PLA General HospitalBeijing 100853China

Chimeric antigen receptor(CAR)T cells have been indicated effective in treating B cell acute lymphoblastic leukemia and non-Hodgkin lymphoma and have shown encouraging results in preclinical and clinical ***,CAR T cells have achieved minimal success against solid malignancies because of the additional obstacles of their insufficient migration into tumors and poor amplification and persistence,in addition to antigen-negative relapse and an immunosuppressive *** preclinical studies are exploring strategies to overcome the above *** of endogenous immune cells is also necessary for CAR T cells to obtain their optimal therapeutic effect given the importance of the innate immune responses in the elimination of malignant *** this review,we focus on the recent advances in the engineering of CAR T cell therapies to restore the immune response in solid malignancies,especially with CAR T cells acting as cellular carriers to deliver immunomodulators to tumors to mobilize the endogenous immune *** also explored the sensitizing effects of conventional treatment approaches,such as chemotherapy and radiotherapy,on CAR T cell ***,we discuss the combination of CAR T cells with biomaterials or oncolytic viruses to enhance the anti-tumor outcomes of CAR T cell therapies in solid tumors.

关键词： CAR T cells immunoregulatory molecules endogenous immune response solid malignancies

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Liver cancer-induced myeloid derived suppressive cells promote tumor metastasis and immune escape

Liver cancer-induced myeloid derived suppressive cells promo...

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第九届全国免疫学学术大会

作者： Yanmei Han Yan Gu Zhubo Chen Zhengping Jiang Yanfang Liu National Key laboratory of Medical Immunology & Institute of Immunology Second Military Medical University

Immune tolerance plays an essential role in the maintenance of immune *** with excessive or prolonged immune activation in the host during inflammation,autoimmune diseases or other immuno-pathologic situations,the immune system has development feedback mechanisms to inhibit immune over-activation and prevent inflammatory *** generation and expansion of immune suppression cell population is one of these *** suppressor cells,with the myeloid makers CD11bGr-1in mice and CD34CD33CD15CD13in human,represent aheterogeneous population of suppressor cells both in tumour-related and tumour-unrelated situations:infection with viruses,bacteria,fungi,and parasites;during immune stress caused by exposure to superantigens or recombinant vaccines;following myelosuppressive treatments by either cyclophosphamide or *** are potent inactivator in CD4and CD8T cells,which are responsible for inhibition of immune over-activation in inflammation and promotion of immune escape in tumour ***,little is known about the differences of MDSCs in immune-activated situation and tumour associated *** describe here a new cell population differented from common MDSCs in tumour mass,Liver cancer-induced MDSC(Li-MDSC),have more powerful potential in immune suppression and induction tumour metastasis by producing *** new cell subset is identified by secreting IL-6 and responsible for tumour induced immune escape and tumour metastasis.

关键词： MDSCs immune escape tumour metastasis MMP-9 IL-6

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