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Global epidemiology of hepatitis C virus infection: an up-date of the distribution and circulation of hepatitis C virus genotypes

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World Journal of Gastroenterology 2016年第34期22卷 7824-7840页

作者： Arnolfo Petruzziello Samantha Marigliano Giovanna Loquercio Anna Cozzolino Carmela Cacciapuoti laboratory of virology and molecular biology "v.tridente" IRCCS Italia

AIM To review Hepatitis C virus(HCv) prevalence and genotypes distribution *** We conducted a systematic study which represents one of the most comprehensive effort to quantify global HCv epidemiology,using the best available published data between 2000 and 2015 from 138 countries(about 90% of the global population),grouped in 20 geographical areas(with the exclusion of Oceania),as defined by the Global Burden of Diseases project(GBD). Countries for which we were unable to obtain HCv genotype prevalence data were excluded from calculations of regional proportions,although their populations were included in the total population size of each region when generating regional genotype prevalence *** Total global HCv prevalence is estimated at 2.5%(177.5 million of HCv infected adults),ranging from 2.9% in Africa and 1.3% in Americas,with a global viraemic rate of 67%(118.9 million of HCv RNA positive cases),varying from 64.4% in Asia to 74.8% in Australasia. HCv genotype 1 is the most prevalent worldwide(49.1%),followed by genotype 3(17.9%),4(16.8%) and 2(11.0%). Genotypes 5 and 6 are responsible for the remaining v genotypes 1 and 3 infections are the most prevalent globally(67.0% if considered together),other genotypes are found more commonly in lowerincome countries where still account for a significant proportion of HCv *** A more precise knowledge of HCv genotype distribution will be helpful to best inform national healthcare models to improve access to new treatments.

关键词： Hepatitis C virus genotype Epidemiology Hepatitis C virus Hepatitis C virus prevalence Hepatitis C virus infections viraemia

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Achievements, challenges and prospects for the development of broadly protective multivalent vaccines and therapeutic antibodies against hand, foot and mouth disease

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Science Bulletin 2015年第15期60卷 1305-1315页

作者： Ke Lyu Rong Chen Key laboratory of molecular virology and Immunology Institut Pasteur of Shanghai Chinese Academy of Sciences

Hand, foot and mouth disease(HFMD) is a significant health concern in the Asia–Pacific regions for infants and young children in recent years. However, no vaccines or therapeutics are available at present. The causative agents for HFMD include human enterovirus 71(Ev71), coxsackievirus A16(CvA16) and some other viruses. Recently, tremendous progress has been made in the development of monovalent and bivalent vaccines against HFMD. A few neutralizing monoclonal antibodies against Ev71 or CvA16 have been identified and characterized. Here, we reviewed some achievements for the development of broadly protective vaccines and neutralizing antibodies against HFMD, and discussed challenges and prospects toward broadly protective multivalent vaccines and therapeutic antibodies against HFMD.

关键词： Hand foot and mouth disease (HFMD) Human enterovirus 71 (Ev71) Coxsackievirus A 16(CvAI6) - vaccine Neutralizing antibodies

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Dr. Chi-Ming Chu： Respected founder of molecular virology and pioneer of biologicals in China

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Protein & Cell 2017年第9期8卷 629-633页

作者： Weizheng Yan Baoying Huang Li Ruan Wenjie Tan Biotech Center for viral Diseases Emergency Key Laboratory of Medical Virology Ministry of Health National Institute for ViralDisease Control and Prevention China CDC Beijing 102206 China

＂I have the greatest respect for Dr. Chu, who upheld great standards of science during very difficult times in China. His contributions to the genetic characterisation of influenza viruses were extraordinary.＂

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Plasma metabolomic and lipidomic alterations associated with COvID-19

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National Science Review 2020年第7期7卷 1157-1168页

作者： Di Wu Ting Shu Xiaobo Yang Jian-Xin Song Mingliang Zhang Chengye Yao Wen Liu Muhan Huang Yuan Yu Qingyu Yang Tingju Zhu Jiqian Xu Jingfang Mu Yaxin Wang Hong Wang Tang Tang Yujie Ren Yongran Wu Shu-Hai Lin Yang Qiu Ding-Yu Zhang You Shang Xi Zhou Joint laboratory of Infectious Diseases and Health Wuhan Institute of Virology & Wuhan Jinyintan Hospital Wuhan Institute of Virology Center for Biosafety Mega-ScienceChinese Academy of Sciences (CAS) State Key laboratory of virology Wuhan Institute of VirologyCenter for Biosafety Mega-Science CAS Center for Translational Medicine Jinyintan Hospital Joint laboratory of Infectious Diseases and Health Wuhan Institute of Virology & Wuhan Jinyintan Hospital Wuhan Jinyintan Hospital Department of Critical Care Medicine Union Hospital Tongji Medical College Huazhong University of Science and Technology Department of Infectious Diseases Tongji Hospital Tongji Medical College Huazhong University of Science and Technology

The pandemic of the coronavirus disease 2019(COvID-19) has become a global public health crisis. The symptoms of COvID-19 range from mild to severe, but the physiological changes associated with COvID-19 are barely understood. In this study, we performed targeted metabolomic and lipidomic analyses of plasma from a cohort of patients with COvID-19 who had experienced different symptoms. We found that metabolite and lipid alterations exhibit apparent correlation with the course of disease in these patients, indicating that the development of COvID-19 affected their whole-body metabolism. In particular, malic acid of the TCA cycle and carbamoyl phosphate of the urea cycle result in altered energy metabolism and hepatic dysfunction, respectively. It should be noted that carbamoyl phosphate is profoundly down-regulated in patients who died compared with patients with mild symptoms. And, more importantly, guanosine monophosphate(GMP), which is mediated not only by GMP synthase but also by CD39 and CD73, is significantly changed between healthy subjects and patients with COvID-19, as well as between the mild and fatal cases. In addition, dyslipidemia was observed in patients with ***, the disturbed metabolic patterns have been found to align with the progress and severity of COvID-19. This work provides valuable knowledge about plasma biomarkers associated with COvID-19 and potential therapeutic targets, as well as an important resource for further studies of the pathogenesis of COvID-19.

关键词： SARS-Co v-2 COvID-19 metabolome lipidome

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Cellular localization of NLRP3 inflammasome

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Protein & Cell 2013年第6期4卷 425-431页

作者： Yan Wang Chen Yang Kairui Mao Shuzhen Chen Guangxun Meng Bing Sun Key laboratory of molecular virology and Immunology Institute Pasteur of ShanghaiShanghai Institutes for Biological SciencesChinese Academy of SciencesShanghai 200025China State Key laboratory of Cell biology Institute of Biochemistry and Cell BiologyShanghai Institutes for Biological SciencesChinese Academy of ScienceShanghai 200031China

Infl ammasome is a large protein complex activated upon cellular stress or microbial infection,which triggers maturation of pro-inflammatory cytokines interleukin-1βand interleukin-18 through caspase-1 ***-like receptor family protein 3(NLRP3)is the most character-ized infl ammasome activated by various ***,the mechanism of its activation is unclear and its exact cellular localization is still *** examined the potential co-localization of NLRP3 infl ammasome with mi-tochondria and seven other organelles under adenosine triphosphate,nigericin or monosodium urate stimulation in mouse peritoneal macrophages using confocal micros-copy *** results revealed that the activated endogenous apoptosis-associated speck-like protein containing a CARD(ASC)pyroptosome forms in the cyto-plasm and co-localizes with NLRP3 and caspase-1,but not with any of the organelles *** study indicates that the ASC pyroptosome universally localizes within the cytoplasm rather than with any specifi c organelles.

关键词： NLRP3 inflammasome ASC pyroptosome confocal microscopy cytoplasmic

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Negative regulation of NLRP3 infl ammasome signaling

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Protein & Cell 2013年第4期4卷 251-258页

作者： Shuzhen Chen Bing Sun State Key laboratory of Cell biology Institute of Biochemistry and Cell BiologyShanghai Institutes of Biological SciencesChinese Academy of SciencesShanghai 200031China Key laboratory of molecular virology&Immunology Institute Pasteur of ShanghaiShanghai Institutes of Biological SciencesChinese Academy of SciencesShanghai 200025China

Infl ammasomes are multiprotein complexes that serve as a platform for caspase-1 activation and interleukin-1β(IL-1β)maturation as well as *** a number of infl ammasomes have been described,the NLRP3 inflammasome is the most extensively ***3 inflammasome is triggered by a variety of stimuli,including infection,tissue damage and metabolic dysregulation,and then activated through an integrated cellular *** regulatory mechanisms have been identifi ed to attenuate NLRP3 infl ammasome signaling at multiple ***,we review the developments in the negative regulation of NLRP3 inflammasome that protect host from inflammatory damage.

关键词： infl ammasome NLRP3 negative regulation infl ammation

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Next-generation sequencing in clinical virology: Discovery of new viruses

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World Journal of virology 2015年第3期4卷 265-276页

作者： Sibnarayan Datta Raghvendra Budhauliya Bidisha Das Soumya Chatterjee vanlalhmuaka vijay veer molecular virology laboratory Defence Research Laboratory (DRDO)

viruses are a cause of significant health problem world-wide, especially in the developing nations. Due to different anthropological activities, human populations are exposed to different viral pathogens, many of which emerge as outbreaks. In such situations, discovery of novel viruses is utmost important for deciding prevention and treatment strategies. Since last century, a number of different virus discovery methods, based on cell culture inoculation, sequence-independent PCR have been used for identification of a variety of viruses. However, the recent emergence and commercial availability of nextgeneration sequencers(NGS) has entirely changed the field of virus discovery. These massively parallel sequencing platforms can sequence a mixture of genetic materials from a very heterogeneous mix, with high sensitivity. Moreover, these platforms work in a sequenceindependent manner, making them ideal tools for virus discovery. However, for their application in clinics, sample preparation or enrichment is necessary to detect low abundance virus populations. A number of techniques have also been developed for enrichment or viral nucleic acids. In this manuscript, we review the evolution of sequencing; NGS technologies available today as well as widely used virus enrichment technologies. We also discuss the challenges associated with their applications in the clinical virus discovery.

关键词： PCR Next-generation sequencers virus discovery Sequence-independent single-primer amplification virus discovery based on cDNA-AFLP Rolling circle amplification Metagenomics

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The nucleoprotein of severe fever with thrombocytopenia syndrome virus processes a stable hexameric ring to facilitate RNA encapsidation

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Protein & Cell 2013年第6期4卷 445-455页

作者： Honggang Zhou Yuna Sun Ying Wang Min Liu Chao Liu Wenming Wang Xiang Liu Le Li Fei Deng Hualin Wang Yu Guo Zhiyong Lou College of Pharmacy and State Key laboratory of Medicinal Chemical biology Nankai UniversityTianjin 300071China laboratory of Structural biology and MOE laboratory of Protein Science School of Medicine and Life SciencesTsinghua UniversityBeijing 100084China State Key laboratory of virology Wuhan Institute of VirologyChinese Academy of SciencesWuhan 430071China National laboratory of Macromolecules Institute of BiophysicsChinese Academy of ScienceBeijing 100101China High-throughput molecular Drug Discovery Center Tianjin Joint Academy of Biotechnology and MedicineTianjin 300457China

Severe fever with thrombocytopenia syndrome virus(SFTSv),a member of the Phlebovirus genus from the Bunyaviridae family endemic to China,is the causative agent of life-threatening severe fever with thrombocyto-penia syndrome(SFTS),which features high fever and *** to other negative-sense RNA viruses,SFTSv encodes a nucleocapsid protein(NP)that is essen-tial for viral *** facilitates viral RNA encapsida-tion and is responsible for the formation of ribonucleopro-tein ***,recent studies have indicated that NP from Phlebovirus members behaves in inhomogene-ous oligomerization *** the present study,we report the crystal structure of SFTSv NP at 2.8Åresolution and demonstrate the mechanism by which it processes a ring-shaped hexameric form to accomplish RNA *** residues essential for oligomerization are identi-fi ed through mutational analysis and identifi ed to have a signifi cant impact on RNA binding,which suggests that correct formation of highly ordered oligomers is a criti-cal step in RNA *** fi ndings of this work provide new insights into the discovery of new antiviral reagents for Phlebovirus infection.

关键词： SFTSv nucleoprotein oligomer RNP as-sembly crystal structure

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Complex positive selection pressures drive the evolution of HIv-1 with different co-receptor tropisms

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Science China(Life Sciences) 2010年第10期53卷 1204-1214页

作者： ZHANG ChiYu DING Na CHEN KePing YANG RongGe Institute of Life Sciences Jiangsu UniversityZhenjiang 212013China HIv molecular Epidemiology and virology Research Group State Key Laboratory of VirologyWuhan Institute of VirologyChinese Academy of SciencesWuhan 430071China

HIv-1 co-receptor tropism is central for understanding the transmission and pathogenesis of HIv-1 infection. We performed a genome-wide comparison between the adaptive evolution of R5 and X4 variants from HIv-1 subtypes B and C. The results showed that R5 and X4 variants experienced differential evolutionary patterns and different HIv-1 genes encountered various positive selection pressures, suggesting that complex selection pressures are driving HIv-1 evolution. Compared with other hypervariable regions of Gp120, significantly more positively selected sites were detected in the v3 region of subtype B X4 variants, v2 region of subtype B R5 variants, and v1 and v4 regions of subtype C X4 variants, indicating an association of positive selection with co-receptor recognition/binding. Intriguingly, a significantly higher proportion (33.3% and 55.6%, Pvely selected sites were identified in the C3 region than other conserved regions of Gp120 in all the analyzed HIv-1 variants, indicating that the C3 region might be more important to HIv-1 adaptation than previously thought. Approximately half of the positively selected sites identified in the env gene were identical between R5 and X4 variants. There were three common positively selected sites (96, 113 and 281) identified in Gp41 of all X4 and R5 variants from subtypes B and C. These sites might not only suggest a functional importance in viral survival and adaptation, but also imply a potential cross-immunogenicity between HIv-1 R5 and X4 variants, which has important implications for AIDS vaccine development.

关键词： HIv-1 co-receptor tropism adaptive evolution positively selected site R5 and X4 Gp120 epitopes

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HIv-1 Protein Tat_(1–72) Impairs Neuronal Dendrites via Activation of PP1 and Regulation of the CREB/BDNF Pathway

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virologica Sinica 2018年第3期33卷 261-269页

作者： Yu Liu Deyu Zhou Jiabin Feng Zhou Liu Yue Hu Chang Liu Xiaohong Kong laboratory of Medical molecular virology School of Medicine Nankai University

Despite the success of combined antiretroviral therapy in recent years, the prevalence of human immunodeficiency virus(HIv)-associated neurocognitive disorders in people living with HIv-1 is increasing, significantly reducing the healthrelated quality of their lives. Although neurons cannot be infected by HIv-1, shed viral proteins such as transactivator of transcription(Tat) can cause dendritic damage. However, the detailed molecular mechanism of Tat-induced neuronal impairment remains unknown. In this study, we first showed that recombinant Tat(1–72 aa) induced neurotoxicity in primary cultured mouse neurons. Second, exposure to Tat_(1–72) was shown to reduce the length and number of dendrites in cultured neurons. Third, Tat_(1–72)(0–6 h) modulates protein phosphatase 1(PP1) expression and enhances its activity by decreasing the phosphorylation level of PP1 at Thr320. Finally, Tat_(1–72)(24 h) downregulates CREB activity and CREBmediated gene(BDNF, c-fos, Egr-1) expression. Together, these findings suggest that Tat_(1–72) might impair cognitive function by regulating the activity of PP1 and the CREB/BDNF pathway.

关键词： Recombinant tat HIv-associated neurocognitive disorders (HAND) - Dendrite impairment - Proteinphosphatase 1 (PP1) CREB/BDNF

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