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Three amino acid residues in the envelope of human immunodeficiency virus type 1 CRF07_BC regulate viral neutralization susceptibility to the human monoclonal neutralizing antibody IgG1b12

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Virologica Sinica 2014年第5期29卷 299-307页

作者： Jianhui Nie Juan Zhao Qingqing Chen Weijin Huang Youchun Wang College of Life Science Jilin University Key laboratory of the Ministry of Health for Research on Quality and Standardization of Biotech Products Division of HIV/AIDS and sex-transmitted virus vaccines National Institutes for Food and Drug Control (NIFDC)

The CD4 binding site(CD4bs) of envelope glycoprotein(Env) is an important conserved target for anti-human immunodeficiency virus type 1(HIV-1) neutralizing antibodies. Neutralizing monoclonal antibodies IgG1 b12(b12) could recognize conformational epitopes that overlap the CD4 bs of Env. Different virus strains, even derived from the same individual, showed distinct neutralization susceptibility to b12. We examined the key amino acid residues affecting b12 neutralization susceptibility using single genome amplification and pseudovirus neutralization assay. Eleven amino acid residues were identified that affect the sensitivity of Env to b12. Through site-directed mutagenesis, an amino acid substitution at position 182 in the V2 region of Env was confirmed to play a key role in regulating the b12 neutralization susceptibility. The introduction of V182 L to a resistant strain enhanced its sensitivity to b12 more than twofold. Correspondingly, the introduction of L182 V to a sensitive strain reduced its sensitivity to b12 more than tenfold. Amino acid substitution at positions 267 and 346 could both enhance the sensitivity to b12 more than twofold. However, no additive effect was observed when the three site mutageneses were introduced into the same strain, and the sensitivity was equivalent to the single V182 L mutation. CRF07_BC is a major circulating recombinant form of HIV-1 prevalent in China. Our data may provide important information for understanding the molecular mechanism regulating the neutralization susceptibility of CRF07_BC viruses to b12 and may be helpful for a vaccine design targeting the CD4 bs epitopes.

关键词： human immunodeficiency virus type 1 CRF07_BC envelope glycoprotein IgG1b12 neutralizing antibody single genome amplification

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Human cytomegalovirus miR-US5-1 inhibits viral replication by targeting Geminin mRNA

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Virologica Sinica 2017年第5期32卷 431-439页

作者： Shujuan Jiang Yujing Huang Ying Qi Rong He Zhongyang Liu Yanping Ma Xin Guo Yaozhong Shao Zhengrong Sun Qiang Ruan Virus Laboratory the Affiliated Shengjing Hospital China Medical University Shenyang 110122 China Clinical Genetics the Affiliated Shengjing Hospital China Medical University Shenyang 110122 China

viruses commonly create favorable cellular conditions for their survival through multiple mechanisms. Micro RNAs(mi RNAs), which function as post-transcriptional regulators, are utilized by human cytomegalovirus(HCMV) in its infection and pathogenesis. In the present study, the DNA replication inhibitor Geminin(GMNN) was identified to be a direct target of hcmv-mi R-US5-1. Overexpression of hcmv-mi R-US5-1 could block the accumulation of GMNN during HCMV infection, and the decrease of GMNN expression caused by hcmv-mi R-US5-1 or GMNN specific si RNA reduced HCMV DNA copies in U373 cells. Meanwhile, ectopic expression of hcmv-mi R-US5-1 and consequent lower expression of GMNN influenced host cell cycle and proliferation. These results imply that hcmv-mi R-US5-1 may affect viral replication and host cellular environment by regulating expression kinetics of GMNN during HCMV infection.

关键词： Human cytomegalovirus(HCMV) hcmv-mi R-US5-1 Geminin(GMNN) DNA replication cell cycle

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Current understanding of Th2 cell differentiation and function

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Protein & Cell 2011年第8期2卷 604-611页

作者： Zhenhu Li Yuan Zhang Bing Sun laboratory of Molecular Cell Biology Institute of Biochemistry and Cell BiologyShanghai Institutes for Biological SciencesChinese Academy of SciencesShanghai 200031China Molecular virus Unit Key Laboratory of Molecular Virology&ImmunologyInstitut Pasteur of ShanghaiChinese Academy of SciencesShanghai 200031China

Helper T cell(Th)has been identified as a critical immune cell for regulating immune response since 1980s.The type 2 helper Tcell(Th2),characterized by the production of interleukin-4(IL-4),IL-5 and IL-13,plays a critical role in immune response against helminths invading cutaneous or mucosal sites.It also has a functional role in the pathophysiology of allergic diseases such as asthma and allergic diarrhea.Currently,most studies have shed light on Th2 cell function and behavior in specific diseases,such as asthma and helminthes inflammation,but not on Th2 cell itself and its differentiation.Based on different cytokines and specific behavior in recent research,Th2 cell is also regarded as new subtypes of T cell,such as IL-9 secreting T cell(Th9)and CXCR5+T follicular helper cells.Here,we will discuss the latest view of Th2 cell towards their function and the involvement of Th2 cell in diseases.

关键词： type 2 helper T cell(Th2) asthma IL-9 secreting T cell(Th9) T follicular helper cell

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Semen extracellular vesicles mediate vertical transmission of subgroup J avian leukosis virus

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Virologica Sinica 2022年第2期37卷 284-294页

作者： Liqin Liao Weiguo Chen Xiangyu Zhang Huanmin Zhang Aijun Li Yiming Yan Zi Xie Hongxing Li Wencheng Lin Jingyun Ma Xinheng Zhang Qingmei Xie Heyuan Branch Guangdong Provincial Laboratory of Lingnan Modern Agricultural Science and TechnologyCollege of Animal ScienceSouth China Agricultural UniversityGuangzhou510642China Guangdong Provincial Key Lab of Agro Animal Genomics and Molecular Breeding Guangzhou510642China USDA Agriculture Research ServiceAvian Disease and Oncology LaboratoryEast LansingMI48823USA College of Science and Engineering Jinan UniversityGuangzhou510632China Key laboratory of Animal Health Aquaculture and Environmental Control GuangdongGuangzhou510642China Guangdong Engineering Research Center for Vector Vaccine of Animal virus Guangzhou510642China

Subgroup J avian leukosis virus(ALV-J) is a highly oncogenic retrovirus that has been devastating the global poultry industry since the late 1990s. The major infection model of ALV-J is vertical transmission, which is responsible for the congenital infection of progeny from generation to generation. Increasing evidence has suggested that extracellular vesicles(EVs) derived from virus-infected cells or biological fluids have been thought to be vehicles of transmission for viruses. However, the role of EVs in infection and transmission of ALV-J remains obscure. In the present study, semen extracellular vesicles(SE) were isolated and purified from ALV-J-infected rooster seminal plasma(SE-ALV-J), which was shown to contain ALV-J genomic RNA and partial viral proteins, as determined by RNA sequencing, reverse transcription-quantitative PCR and Western blotting. Furthermore, SE-ALV-J was proved to be able to transmit ALV-J infection to host cells and establish productive infection.More importantly, artificial insemination experiments showed that SE-ALV-J transmitted ALV-J infection to SPF hens, and subsequently mediated vertical transmission of ALV-J from the SPF hens to the progeny chicks. Taken together, the results of the present study suggested that ALV-J utilized host semen extracellular vesicles as a novel means for vertical transmission, enhancing our understanding on mechanisms underlying ALV-J transmission.

关键词： Semen extracellular vesicles(SE) Subgroup J avian leukosis virus(ALV-J) Infection Vertical transmission

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Synthesis and biological evaluation of novel tricyclic matrinic derivatives as potential anti-filovirus agents

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Acta Pharmaceutica Sinica B 2018年第4期8卷 629-638页

作者： Xin Zhang Qiang Liu Qianqian Li Yinghong Li Zhandong Liu Hongbin Deng Sheng Tang Yanxiang Wang Youchun Wang Danqing Song Beijing Key laboratory of Antimicrobial Agents Institute of Medicinal BiotechnologyChinese Academy of Medical Science & Peking Union Medical College Division of HIV/AIDS and Sex-transmitted virus Vaccines National Institutes for Food and Drug Control Department of Neurology Beijing Friendship HospitalCapital Medical University

Twenty-six novel tricyclic sophoridinic and matrinic derivatives containing a common chlorinated benzene fragment were designed, synthesized and evaluated for their anti-ebolavirus(EBOV)activities. Structure–activity relationship analysis indicated:(i) 12 N-dichlorobenzyl motif was beneficial for the activity;(ii) the chiral configuration at C5 atom might not affect the activity much. Among the target compounds, compound 7d exhibited the most potent potency against EBOV with an IC_(50) value of 5.29 μmol/L and an SI value of over 37.8. Further in vivo anti-EBOV assay of 7d identified its high effectiveness, and in vivo anti-MARV assay of 7d suggested its inspiring broad-spectrum anti-filovirus activity. The results provided powerful information on further strategic optimization and development of this kind of compounds against filoviruses.

关键词： Sophoridinic Matrinic Structure-activity relationship EBOV Filovirus

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HIV-1感染的小动物模型

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中国实验动物学报 2005年第S1期13卷 9-10页

作者： Yoshio Koyanagi laboratory of Viral Pathogenesis Institute for Virus ResearchKyoto University Kyoto 606-8507 Japan

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AGO2a but not AGO2b mediates antiviral defense against infection of wild-type cucumber mosaic virus in tomato

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Horticulture Research 2023年第5期10卷 38-48页

作者： Liling Zhao Yingfang Chen Xingming Xiao Haiying Gao Jiamin Cao Zhongkai Zhang Zhongxin Guo Vector-borne virus Research Center State Key Laboratory for Ecological Pest Control of Fujian and Taiwan CropsCollege of Plant ProtectionFujian Agriculture and Forestry UniversityFuzhou 350002 China 2Key laboratory of Agricultural Biotechnology of Yunnan Province Biotechnology and Germplasm Resources Research InstituteYunnan Academy of Agricultural SciencesKunming650221 China

Evolutionarily conserved antiviral RNA interference(RNAi)mediates a primary antiviral innate immunity preventing infection of broad-spectrum viruses in plants.However,the detailed mechanism in plants is still largely unknown,especially in important agricultural crops,including tomato.Varieties of pathogenic viruses evolve to possess viral suppressors of RNA silencing(VSRs)to suppress antiviral RNAi in the host.Due to the prevalence of VSRs,it is still unknown whether antiviral RNAi truly functions to prevent invasion by natural wild-type viruses in plants and animals.In this research,for the first time we applied CRISPR-Cas9 to generate ago2a,ago2b,or ago2ab mutants for two differentiated Solanum lycopersicum AGO2s,key effectors in antiviral RNAi.We found that AGO2a but not AGO2b was significantly induced to inhibit the propagation of not only VSR-deficient Cucumber mosaic virus(CMV)but also wild-type CMV-Fny in tomato;however,neither AGO2a nor AGO2b regulated disease induction after infection with either virus.Our findings firstly reveal a prominent role of AGO2a in antiviral RNAi innate immunity in tomato and demonstrate that antiviral RNAi evolves to defend against infection of natural wild-type CMV-Fny in tomato.However,AGO2a-mediated antiviral RNAi does not play major roles in promoting tolerance of tomato plants to CMV infection for maintaining health.

关键词： immunity invasion media

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Current rice production is highly vulnerable to insect-borne viral diseases

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National Science Review 2022年第9期9卷 142-144页

作者： Jian-guo Wu Guo-yi Yang Shan-shan Zhao Shuai Zhang Bi-xia Qin Yong-sheng Zhu Hui-ting Xie Qing Chang Lu Wang Jie Hu Chao Zhang Bao-gang Zhang Da-li Zeng Jian-fu Zhang Xian-bo Huang Qian Qian Shou-wei Ding Yi Li Vector-borne virus Research Center Fujian Province Key Laboratory of Plant Virology Institute of Plant Virology Fujian Agriculture and Forestry University Institute of Plant Protection Guangxi Academy of Agricultural Sciences Rice Research Institute Fujian Academy of Agricultural Sciences State Key laboratory of Rice Biology China National Rice Research InstituteChinese Academy of Agricultural Sciences Rice Research Institute Sanming Academy of Agricultural Sciences Department of Microbiology and Plant Pathology Center for Plant Cell Biology Institute for Integrative Genome Biology University of California The State Key laboratory of Protein and Plant Gene Research School of Life Sciences Peking University

Rice is one of the most important food crops and feeds more than half of the world’s population [1]. Arthropod-borne rice viruses have caused devastating epidemics in Asian countries and are a major threat to food security [2]. However,lile is known about the vulnerability of rice crops to viral pathogens [3,4], especially southern rice black-streaked dwarf virus (SRBSDV), rice black-streaked dwarf virus (RBSDV) and rice gall dwarf virus (RGDV), known to induce annual outbreaks by insect transmission in some localities in Asia.

关键词： INSIGHTS IMMUNITY

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Viral Regulation of RNA Granules in Infected Cells

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Virologica Sinica 2019年第2期34卷 175-191页

作者： Qiang Zhang Nishi R. Sharma Zhi-Ming Zheng Mingzhou Chen State Key laboratory of Virology and Modern Virology Research Center College of Life Sciences Wuhan UniversityWuhan 430072 China Tumor virus RNA Biology Section RNA Biology Laboratory National Cancer Institute National Institutes of Health Frederick MD 21702 USA

RNA granules are cytoplasmic, microscopically visible, non-membrane ribo-nucleoprotein structures and are important posttranscriptional regulators in gene expression by controlling RNA translation and stability. TIA/G3BP/PABP-specific stress granules(SG) and GW182/DCP-specific RNA processing bodies(PB) are two major distinguishable RNA granules in somatic cells and contain various ribosomal subunits, translation factors, scaffold proteins, RNA-binding proteins, RNA decay enzymes and helicases to exclude m RNAs from the cellular active translational pool. Although SG formation is inducible due to cellular stress, PB exist physiologically in every cell. Both RNA granules are important components of the host antiviral defense. virus infection imposes stress on host cells and thus induces SG formation. However, both RNA and DNA viruses must confront the hostile environment of host innate immunity and apply various strategies to block the formation of SG and PB for their effective infection and multiplication. This review summarizes the current research development in the field and the mechanisms of how individual viruses suppress the formation of host SG and PB for virus production.

关键词： Stress granules (SG) P-bodies (PB) RNA virus - DNA virus

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Galectin-7 overexpression destroys airway epithelial barrier in transgenic mice

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Integrative Zoology 2021年第2期16卷 270-279页

作者： Jing TIAN Ruxuan HE Yimu FAN Qianqian ZHANG Baolin TIAN Chunju ZHOU Chunyan LIU Mingjing SONG Shunying ZHAO Department of Respiratory Medicine II Beijing Children’s HospitalCapital Medical UniversityNational Center for Children’s HealthBeijingChina Virus Laboratory Beijing Children’s HospitalCapital Medical UniversityNational Center for Children’s HealthChina Key laboratory of Human Disease Comparative Medicine National Health Commission of China(NHC)Beijing Engineering Research Center for Experimental Animal Models of Human DiseasesInstitute of Laboratory Animal SciencePeking Union Medicine CollegeChinese Academy of Medical SciencesBeijingChina

When the integrity of airway epithelium is destroyed,the ordered airway barrier no longer exists and increases sensitivity to viral infections and allergens,leading to the occurrence of airway inflammation such as asthma.Here,we found that galectin-7 transgenic(+)mice exhibited abnormal airway structures as embryos and after birth.These abnormalities included absent or substantially reduced pseudostratified columnar ciliated epithelium and increased monolayer cells with irregular arrangement and widening of intercellular spaces.Moreover,airway tissue from galectin-7 transgenic(+)mice showed evidence of impaired cell–cell junctions and decreased expression of zonula occludens-1(ZO-1)and E-cadherin.When treated with respiratory syncytial virus(RSV)or ovalbumin(OVA),galectin-7 transgenic(+)mice developed substantially increased bronchial epithelial detachment and apoptosis,airway smooth muscle and basement membrane thickening,and enhanced airway responsiveness.We found that Galectin-7 localized in the cytoplasm and nucleus of bronchial epithelial cells,and that increased apoptosis was mediated through mitochondrial release of cytochrome c and upregulated JNK1 activation and expression of caspase-3 in galectin-7 Tg(+)mice.These findings suggested that Galectin-7 causes airway structural defects and destroys airway epithelium barrier,which predispose the airways to RSV or OVA-induced epithelial apoptosis,injury,and other asthma responses.

关键词： airway epithelial barrier epithelial apoptosis galectin-7

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