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2018年33卷5期

Nipah virus (NiV), a zoonotic paramyxovirus belonging to the genus Henipavirus, is classified as a Biosafety Level-4 pathogen based on its high pathogenicity in humans and the lack of available vaccines or therapeutics. Since its initial emergence in 1998 in Malaysia, this virus has been reported in Asia, Africa, and the South Pacific Ocean. NiV has a wide range of hosts, from its natural reservoir Pteropid bats to humans, horses, dogs, cats, cows, and pigs. NiV spreads from bats to humans through two main pathways, intermediate hosts (pigs and horses) and food-borne transmission via date palm sap contaminated with the saliva or urine of fruit bats. In this issue, Sun et al. reviewed the recent studies on the geographical and phylogenetic properties, transmission, and protein structure and function of NiV. The cover image is provided courtesy of Bangyao Sun and Di Liu. (See Page 385-393 for details).

EDITORIAL

Professor Hu Zhihong: The New President of the Society for Invertebrate Pathology

ArifBasil, SiJiali, ShiZheng-Li

2018, 33(5): 383 doi: 10.1007/s12250-018-0060-z

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The Society for Invertebrate Pathology (SIP) is foremost in the world covering all aspects of related research in insect virology, bacteriology, mycology, parasitology and microbial control. The SIP has a wide scientific appeal with members from many countries spanning every continent in the globe. Election of members to the Society's Governing Council is based on scientific standing, contributions, reputation and involvement in the activities of the Society. At the recent annual meeting in August 2018, in the Gold Coast of Australia, Prof. Hu Zhihong was inaugurated as the President of the SIP having been elected by worldwide members to take charge of the Society's activities, direction and scientific standing. Prof. Hu's qualifications as a scientist and a leader are impeccable and far-reaching. Her outstanding scientific achievements, salient contributions to the field of virology and innovative approaches to research made her a world-renowned scientist. She has so far published no less than 150 manuscripts, mostly in internationally refereed scientific journals. Her contributed and invited presentations at the annual meetings of the Society often reflected the state-of-the-art in molecular virology. All this gave members of the SIP ample reasons to elect her as the President. Her experience as a past Director General of the Wuhan Institute of Virology of the Chinese Academy of Sciences will help her immensely in running and directing the SIP to achieve even greater heights. No doubt, she will be an exceptional President.
REVIEW

尼帕病毒的系统发生地理学、传播和病毒蛋白

孙邦耀, 贾李佳, 梁碧林, 陈全姣, 刘翟

2018, 33(5): 385 doi: 10.1007/s12250-018-0050-1

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尼帕病毒是一种危害极大的人兽共患病病毒,属于副粘病毒科亨尼帕病毒属。由于其在人类的高致病性且缺乏有效的疫苗或治疗方法,因此被归类为生物安全4级病原。自1998年在马来西亚首次出现以来,尼帕病毒已经导致了数百人死亡,严重威胁着家畜和人类健康。流行病学调查显示,尼帕病毒由其自然宿主蝙蝠传播,现已分布在亚洲、非洲和南太平洋。目前科学家们已针对病毒蛋白质的功能和结构进行了大量的研究,希望借此开发出有效的抗病毒药物。同时,对尼帕病毒的流行病学监测也亟待加强。
Research Article

不同进化分支塞内卡病毒在我国广东省的流行

陈盼, 杨帆, 曹伟军, 刘华南, 张克山, 刘湘涛, 徐志文, 朱紫祥, 郑海学

2018, 33(5): 394 doi: 10.1007/s12250-018-0056-8

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塞内卡病毒病是由塞内卡病毒引起的猪的新发传染病,其能够引发猪的原发性水泡病和小猪的急性死亡。近年来,该病在美国、中国等地不断蔓延发生,对养猪业造成了巨大危害。我国于2015年首次在广东省鉴定了塞内卡病毒的传入,在2015及2016年期间接连发现了该病在广东省不同地区的发生和流行。然而关于该病在2017年的流行情况仍不清楚。本研究鉴定了两株广东省2017年流行的塞内卡病毒株,并对其全基因组进行了测定,对其遗传特性进行了分析。结果发现2017年流行的毒株与2015和2016年毒株相比其同源性较低,而其与美国新发毒株同源性较高,其进化分支也与2015和2016年广东毒株不在同一分支,与美国毒株处于同一分支。2017年毒株与2015年毒株相比,存在28个氨基酸的变异。本研究表明塞内卡病毒仍然在广东省持续流行,而且出现了处于两个不同进化分支的毒株。

EBV和 HHV6病毒共感染于Rasmussen脑炎脑组织的研究发现

刘东, 王鑫, 王一松, 王培刚, 范东嬴, 陈思畅, 关宇光, 李天富, 安静, 栾国明

2018, 33(5): 402 doi: 10.1007/s12250-018-0063-9

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Rasmussen脑炎是一种罕见的儿童神经系统疾病,确切的病因尚不清楚。然而,研究发现病毒感染被认为是RE发病的诱因。本研究利用免疫组织化学方法对30例RE患者和16例对照组脑组织中EB病毒 (EBV) 和人疱疹病毒 (HHV)6型抗原表达进行检测,结果发现在RE组中EBV和HHV 6抗原检出率分别为 56.7% (17/30) 和 50% (15/30),对照组中无EBV和HHV 6抗原的表达。同时,EBV和HHV 6在RE患者组中共同表达率为20.0%(6/30)。本文介绍了一个4岁男孩的典型临床病例,它具有病毒性脑炎病史,顽固性癫痫和半球萎缩等特点,EBV和 HHV 6在其脑组织神经元和星形胶质细胞中均得到检出,且伴有大量CD8 阳性T细胞表达,结果提示EBV, HHV 6感染及CD8 T细胞活化参与了RE的发病。

Countrywide Survey for MERS-Coronavirus Antibodies in Dromedaries and Humans in Pakistan

ZohaibAli, SaqibMuhammad, AtharMuhammad Ammar, ChenJing, SialAwais-ur-Rahman, KhanSaeed, TajZeeshan, SadiaHalima, TahirUsman, TayyabMuhammad Haleem, QureshiMuhammad Asif, MansoorMuhammad Khalid, NaeemMuhammad Ahsan, HuBing-Jie, KhanBilal Ahmed, UjjanIkram Din, LiBei, ZhangWei, LuoYun, ZhuYan, WaruhiuCecilia, KhanIahtasham, YangXing-Lou, SajidMuhammad Sohail, CormanVictor Max, YanBing, ShiZheng-Li

2018, 33(5): 410 doi: 10.1007/s12250-018-0051-0

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Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a zoonotic pathogen capable of causing severe respiratory disease in humans. Although dromedary camels are considered as a major reservoir host, the MERS-CoV infection dynamics in camels are not fully understood. Through surveillance in Pakistan, nasal (n=776) and serum (n=1050) samples were collected from camels between November 2015 and February 2018. Samples were collected from animal markets, free-roaming herds and abattoirs. An in-house ELISA was developed to detect IgG against MERS-CoV. A total of 794 camels were found seropositive for MERS-CoV. Prevalence increased with the age and the highest seroprevalence was recorded in camels aged > 10 years (81.37%) followed by those aged 3.1-10 years (78.65%) and ≤ 3 years (58.19%). Higher prevalence was observed in female (78.13%) as compared to male (70.70%). Of the camel nasal swabs, 22 were found to be positive by RT-qPCR though with high Ct values. Moreover, 2,409 human serum samples were also collected from four provinces of Pakistan during 2016-2017. Among the sampled population, 840 humans were camel herders. Although we found a high rate of MERS-CoV antibody positive dromedaries (75.62%) in Pakistan, no neutralizing antibodies were detected in humans with and without contact to camels.

组蛋白去乙酰化酶3抑制剂通过调控Apo-A1和LEAP-1表达抑制丙型肝炎病毒复制

周缘, 王倩, 杨琪, 唐婕琳, 许崇辉, 盖冬玮, 陈新文, 陈继征

2018, 33(5): 418 doi: 10.1007/s12250-018-0057-7

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组蛋白去乙酰化酶(HDAC)抑制剂在临床上用于治疗癌症如肝癌。在本研究中,我们研究了HDAC抑制剂在细胞水平及动物水平对丙型肝炎病毒(HCV)复制的影响。在浓度低于1 mmol/L时,HDAC3抑制剂显著抑制HCV复制且没有细胞毒性。通过基因芯片和荧光定量PCR分析,HDAC3抑制剂会导致HCV负相关蛋白肝脏抗菌肽1(LEAP-1)上调,正相关蛋白载脂蛋白a1 (Apo-A1)下调,从而抑制HCV复制。进一步的机制研究显示,HDAC3通过调节 C / EBPα,低氧诱导因子1α(HIF1α)和信号传感器和转录激活3(STAT3)的乙酰化修饰影响它们的LEAP-1启动子的结合能力。HDAC3抑制剂证明在HCV小鼠模型也有治疗效果。这些结果表明,HDAC3抑制剂可能是HCV感染相关疾病(如HCC)的一种潜在治疗方法。

猪繁殖与呼吸综合征病毒非结构蛋白nsp8是病毒RNA依赖的RNA聚合酶的N端的鉴定

刘园园, 胡云皓, 柴悦, 刘莉萍, 宋江伟, 周少川, 苏佳, 周磊, 盖新娜, 郭鑫, 韩军, 杨汉春

2018, 33(5): 429 doi: 10.1007/s12250-018-0054-x

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猪繁殖与呼吸综合征病毒(PRRSV)为单股正链RNA病毒,属套式病毒目动脉炎病毒科成员,其复制涉及表达开放阅读框ORF1a和ORF1b编码的复制酶多聚蛋白。非结构蛋白nsp9为病毒RNA依赖的RNA聚合酶,是ORF1b编码的第一个复制酶蛋白,而nsp8位于ORF1a编码的多聚蛋白C端。由于ORF1b的表达依赖于 -1型核糖体移码翻译机制,nsp9的翻译为nsp8羧基端的自然延伸。然而,在PRRSV感染的细胞内,成熟形式的nsp9是否仍然包含nsp8尚不清楚。利用针对nsp8和nsp9的特异性抗体,我们发现:(1)在病毒感染的细胞内,PRRSV nsp9主要位于72 kDa和95 kDa之间 (72-95 KD),其迁移率与体外瞬时表达的nsp8-9ORF1b一致,但小于ORF1b编码的nsp9(nsp9ORF1b);(2)针对nsp8的抗体能检测到72-95 KD 大小的nsp9条带, 而nsp7和nsp10抗体则不能。而且,在免疫沉淀试验中,nsp9能够被nsp8抗体沉淀,反之亦然;(3)Nsp4和nsp2 PLP2蛋白酶都不能够切割nsp8-9。综上,本研究为nsp8是nsp9 N端的假说提供了直接的实验证据,这一结果为进一步阐明PRRSV nsp9的生物学功能奠定了良好的基础。

Cyclophilin A调控AIP4介导的A型流感病毒M1蛋白的泛素化

马迪娜·马合苏提汗, 郑伟楠, 崔亮, 李芸, 焦鹏涛, 杨文贤, 刘薇, 李晶, 范文辉, 杨利敏, 刘文军, 孙蕾

2018, 33(5): 440 doi: 10.1007/s12250-018-0058-6

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Cyclophilin A (CypA,亲环素A)是一种肽基脯氨酰顺反异构酶,能够与A型流感病毒M1蛋白相互作用,通过调控M1的泛素-蛋白酶体途径的降解来抑制病毒的复制。然而,CypA调控M1蛋白泛素化的机制尚不清楚。我们发现 E3连接酶AIP4能够促进M1在K102和K104位点的泛素化,并加速M1的泛素-蛋白酶体途径的降解。K102R/K104R突变导致重组病毒无法拯救,表明M1在K102和K104位点的泛素化是病毒复制所必需的。进一步研究表明,CypA能够破坏AIP4与M1的相互作用,抑制AIP4介导的M1泛素化。更为重要的是,K102R/K104R突变及CypA均能够抑制M1的出核,表明CypA通过调控AIP4介导的M1在K102和K104位点的泛素化抑制M1的出核,进而影响流感病毒的复制。本研究揭示了CypA通过调控M1泛素化来影响流感病毒复制的机制。
LETTERS

Characterization of Avian-like Influenza A (H4N6) Virus Isolated from Caspian Seal in 2012

GulyaevaMarina, SobolevIvan, SharshovKirill, KurskayaOlga, AlekseevAlexander, ShestopalovaLidia, KovnerAnna, BiYuhai, ShiWeifeng, ShchelkanovMichael, ShestopalovAlexander

2018, 33(5): 449 doi: 10.1007/s12250-018-0053-y

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Marine mammals are widely distributed and can be found almost in all coastal waters and coastlines around the world. The interface areas between marine and terrestrial environments provide natural habitats for aquatic and semiaquatic mammals as well as for reservoir species of avian influenza viruses (AIV) (Runstadler et al. 2013). Previous studies showed that wild aquatic birds, the natural reservoir of AIV, are able to transmit the virus to various mammals, including seals, swine, horses, muskrats, and humans (Webster et al. 1992; Reperant et al. 2009; Gulyaeva et al. 2017). Close contacts between sea mammals and wild birds on breeding-grounds could promote both interspecies transmission of AIV and virus establishment in a new host (Fereidouni et al. 2014). Various AIV subtypes (A/seal/ Massachusetts/80(H7N7), A/Seal/MA/133/82(H4N5), A/Seal/MA/3807/91(H4N6), A/Seal/MA/3911/92(H3N3), A/harbour seal/Mass/1/2011(H3N8) and A/harbor seal/NL/ PV14-221_ThS/2015(H10N7) etc.) have been isolated from different species of marine mammals during the last 30 years. AIV isolated from marine mammals and wild birds are closely related, which suggests that wild birds are the major source of AIV infection (Fereidouni et al. 2014; Bodewes et al. 2015). In addition, AIV can cross species barrier and replicate well in experimental mammals without prior adaptation (Driskell et al. 2012).

中东呼吸综合征冠状病毒的嵌合型病毒样颗粒疫苗在小鼠体内诱导了有效的抗体反应

蓝佳明, 邓瑶, 宋敬东, 黄保英, 王文玲, 谭文杰

2018, 33(5): 453 doi: 10.1007/s12250-018-0064-8

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中东呼吸综合征冠状病毒是新近发现的一种冠状病毒,感染人体后导致较高的病死率,然而目前尚无有效的疫苗或药物防治其引起的感染。病毒样颗粒含有病毒的主要结构蛋白,进入机体后可诱导高效的免疫应答反应,是一种安全有效的疫苗。本研究以流感病毒H5N1的基质蛋白M1为核心,表面镶嵌中东呼吸综合征冠状病毒的棘突蛋白S,在杆状病毒昆虫细胞表达系统内包装了该病毒的嵌合型病毒样颗粒。电镜下该嵌合型病毒样颗粒和野生型中东呼吸综合征冠状病毒形态相似,均为球形,直径在100nm左右。将该病毒样颗粒免疫小鼠,发现其在小鼠体内诱导了高滴度的S蛋白特异性IgG抗体以及有效的中和抗体应答。该嵌合型病毒样颗粒有望进一步开发为有效的疫苗预防中东呼吸综合征冠状病毒引起的感染。
PERSPECTIVE

常见疱疹病毒HHV-6A/7感染是阿兹海默症的元凶?

王玉燕, 丁玲, 朱青, 束敏峰, 蔡启良

2018, 33(5): 456 doi: 10.1007/s12250-018-0049-7

[HTML全文] [PDF 465 KB] Springerlink
Joel Dudley及其同事在神经学领域国际顶级杂志《Neuron》7月11日在线发表了一项最新研究结果显示了,HHV-6A和HHV-7均可能是阿兹海默症AD的重要致病因子。然而,鉴于各种生物学和相关技术局限性,我们回顾了仅目前数据情况下确定HHV-6A和HHV-7感染与AD之间病因关系的复杂性,并着重展望了未来后续工作潜在的研究方向。

靶向细胞凋亡抑制蛋白,一种慢乙肝功能性治愈的新选择?

刘红艳, 侯金林, 张小勇

2018, 33(5): 459 doi: 10.1007/s12250-018-0062-x

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乙型肝炎病毒感染仍然是当前全球性的公共卫生问题,本篇文章讨论了细胞凋亡抑制蛋白cIAPs作为乙肝功能性治愈新靶点的合理性和可能性,同时介绍了正在进行的cIAPs拮抗剂APG-1387治疗慢乙肝患者的1期临床试验。