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2018年33卷4期

Stress granules (SGs) are intracellular granules formed when cellular translation is blocked. Viral infections can induce the formation of SGs, which in turn promote or inhibit viral infection. In this issue, Xia Zhai et al. investigated the effect of coxsackievirus B type 3 (CVB3) infection on SG formation, and found that CVB3 could induce SG formation in the early phase of infection, while SGs could in turn restrict the biosynthesis of CVB3 in host cells. The cover image shows the formation of stress granules (green dots) in HeLa cells infected with CVB3 (red) for 6 h (kindly provided by Prof. Zhaohua Zhong). See page 314–322 for details.

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Research Article

Hepatitis C in Laos: A 7-Year Retrospective Study on 1765 Patients

2018, 33(4): 295 doi: 10.1007/s12250-018-0039-9

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Hepatitis C (HCV) is a global health concern, notably in Southeast Asia, and in Laos the presentation of the disease is poorly known. Our objective was thus to describe a comprehensive HCV infection pattern in order to guide national health policies. A study on a group of 1,765 patients formerly diagnosed by rapid test in health centres was conducted at the Centre of Infectiology Lao Christophe Merieux in Vientiane. The demographic information of patients, their infection status (viral load: VL), liver function (aminotransferases) and treatments were analysed. Results showed that gender distribution of infected people was balanced; with median ages of 53.8 for men and 51.6 years for women (13–86 years). The majority of patients (72%) were confirmed positive (VL > 50 IU/mL) and 28 % of them had high VL (> 6log10). About 23% of patients had level of aminotransferases indicative of liver damage (> 40 IU/mL); but less than 20 % of patients received treatment. Patients rarely received a second sampling or medical imaging. The survey also showed that cycloferon, pegylated interferon and ribavirin were the drugs prescribed preferentially by the medical staff, without following any international recommendations schemes. In conclusion, we recommend that a population screening policy and better management of patients should be urgently implemented in the country, respecting official guidelines. However, the cost of biological analysis and treatment are significant barriers that must be removed. Public health resolutions should be immediately enforced in the perspective of meeting the WHO HCV elimination deadline by 2030.

Molecular-Genetic Characterization of Human Rotavirus A Strains Circulating in Moscow, Russia (2009–2014)

2018, 33(4): 304 doi: 10.1007/s12250-018-0043-0

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Enteric viruses are the most common cause of acute gastroenteritis (AGE) in young children and a significant public health problem globally. Hospital admissions of children under 5 years of age with diarrhea are primarily associated with group A rotavirus (RVA) infection. In this retrospective study, the population structure of viruses linked to AGE etiology in young children hospitalized with AGE in Moscow was evaluated, and molecular characterization of RVA strains was performed. Fecal specimens were collected from children under 5 years old hospitalized with AGE between 2009 and 2014 in Moscow, Russia. Multiplex real-time reverse transcription PCR was used to detect enteric viruses and for G/[P]-genotyping of isolated RVAs. Sequencing of RVA VP7 and VP4 cDNA fragments was used to validate the data obtained by PCRgenotyping. The main causes for hospitalization of children with AGE were RVA (40.1%), followed by noroviruses (11.4%), while adenoviruses, astroviruses, sapoviruses, enteroviruses, and orthoreoviruses were detected in 4.7%, 1.9%, 1.4%, 1.2%, and 0.2% of samples tested, respectively. Nosocomial infections, predominantly associated with RVAs and noroviruses, were detected in 24.8% of cases and occurred significantly more frequently in younger infants. The predominant RVA genotype was G4P[8], detected in 38.7% of RVA-positive cases, whereas genotypes G1P[8], G9P[8], G3P[8], and G2P[4] were found in 11.8%, 6.6%, 4.2%, and 3.3% of cases, respectively. Together, the presence of circulating RVA strains with rare VP7 and VP4 gene variants (G6 and P[9]) highlights the need to conduct continuous epidemiological monitoring of RVA infection.

应激颗粒是宿主细胞对B组柯萨奇病毒感染的早期抗病毒机制之一

翟霞, 吴硕, 林乐勋, 王天楹, 钟晓岩, 陈阳, 徐维祯, 佟雷, 王燕, 赵文然, 钟照华

2018, 33(4): 314 doi: 10.1007/s12250-018-0040-3

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应激颗粒(Stress granule, SG)是细胞的蛋白质合成受阻时形成的、由RNA及RNA结合蛋白构成的细胞质聚集体。SG的形成与多种疾病包括病毒感染相关。我们之前的研究发现B组柯萨奇病毒(Coxsackievirus B,CVB)感染时有SG的形成,但SG的形成对CVB感染的影响则不清楚。本研究发现,SG的形成发生在CVB感染的早期;在这一阶段,促进SG形成的因素显著抑制了CVB的RNA与蛋白质的合成;而用干扰RNA抑制G3BP1 和 TIA1的表达从而阻断SG形成时,可以解除对CVB生物合成的抑制。我们的研究提示,SG的形成是宿主细胞应对CVB病毒感染的早期抗病毒抑制之一。

塞拉利昂埃博拉疫情后期实验室确诊和疑似埃博拉病毒患者的血清学评估

刘洋, 孙玉兰, 芜为, 李阿茜, 杨显达, 张硕, 李川, 苏秋东, 蔡少建, 孙大鹏, 胡海洋, 张哲, 杨秀旭, 李建东, 王世文, 董小平, 舒跃龙, 许文波, 高福, 武桂珍, 李德新, 刘军, 梁米芳,

2018, 33(4): 323 doi: 10.1007/s12250-018-0044-z

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本研究旨在调查塞拉利昂埃博拉疫情后期埃博拉病毒感染的血清学特征。从2015年3月至12月,对共694例疑似埃博拉病毒病病例的877例血液样本进行分析,利用实时荧光RT-PCR检测病毒RNA,利用酶联免疫吸附试验(ELISA)和Luminex检测埃博拉病毒特异性抗体。在2015年3月至12月期间,埃博拉病毒载量和特异性IgM/IgG滴度呈整体下降趋势。在发病后早期,病毒RNA载量迅速下降。而确诊的EVD病例中,埃博拉病毒特异性IgM和IgG抗体阳性分别占58.1%(18/31)和93.5%(29/31),RNA阴性的疑似病例中IgM和IgG抗体阳性分别占3.8%(25/663)和17.8%(118/663)。对连续采集标本的8例EVD患者的样本进行动态分析后发现,呈现典型的埃博拉病毒感染的病毒血症和抗体反应变化趋势,即病毒载量下降和IgM / IgG滴度增加。本研究结果表明,在疫情后期,塞拉利昂的某些人群对埃博拉病毒感染产生了免疫力,为人群中埃博拉病毒感染的风险评估提供了新的见解。

Tandem 3' UTR Patterns and Gene Expression Profiles of Marc-145 Cells During PRRSV Infection

2018, 33(4): 335 doi: 10.1007/s12250-018-0045-y

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Porcine reproductive and respiratory syndrome virus (PRRSV) causes substantial economic losses to the global pig industry. Alternative polyadenylation (APA) is a mechanism that diversifies gene expression, which is important for tumorigenesis, development, and cell differentiation. However, it is unclear whether APA plays a role in the course of PRRSV infection. To address this issue, in this study we carried out a whole-genome transcriptome analysis of PRRSVinfected Marc-145 African green monkey kidney cells and identified 185 APA switching genes and 393 differentially expressed genes (DEGs). Most of these genes were involved in cellular process, metabolism, and biological regulation, and there was some overlap between the two gene sets. DEGs were found to be more directly involved in the antiviral response than APA genes. These findings provide insight into the dynamics of host gene regulation during PRRSV infection and a basis for elucidating the pathogenesis of PRRSV.

杆状病毒诱导舞毒蛾幼虫行为改变阶段基因表达模式研究

李凤佼, 王敦,

2018, 33(4): 345 doi: 10.1007/s12250-018-0046-x

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杆状病毒是一类对害虫生防效果良好的微生物。杆状病毒不仅在感染昆虫过程中影响到宿主的免疫,同时也会改变昆虫的行为。一些研究从病毒的角度去探讨病毒感染引起宿主昆虫行为变化的机理,但针对这种行为变化,尚无从宿主昆虫角度去探究基因表达变化与之相关性的研究。舞毒蛾核型多角体病毒诱导被感染的幼虫在染病后3天 到6天发生显著的行为变化。本研究对感病和健康幼虫转录组数据进行分析,以期寻找与行为变化相关的基因调控途径。基因功能与富集分析发现多数差异基因与蛋白酶解、胞外区和丝氨酸蛋白酶相关。通过KEGG和基因富集分析分析得到类似的结果,其中富集度较高的有487 个信号传导相关基因和85个神经配体、受体互作的基因。而基因富集图表明神经配体与受体互作基因及一些其他功能基因与肌肉功能协调反应存在关联,这对解释昆虫受病毒感染后的行为变化提供了重要线索。所有的神经配体与受体互作差异基因均为丝氨酸蛋白酶,并且这些酶在宿主感病阶段的表达谱差异与病毒诱导宿主行为变化过程一致。这些发现为深入理解舞毒蛾幼虫感病后行为变化的机理提供了基础数据,有助于最终找到LdMNPV调控感病幼虫行为中的重要宿主因子。

波纹杂毛虫核型多角体病毒基因组特性的研究:一株新型的Alpha属组I杆状病毒

朱铮, 王君, 王倩然, 尹飞飞, 刘小萍, 候典海, 张磊, 刘海舟, 李江, 王华林, 邓菲, 胡志红, 王曼丽,

2018, 33(4): 359 doi: 10.1007/s12250-018-0047-9

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波纹杂毛虫核型多角体病毒(CyunNPV)是一种分离自森林害虫波纹杂毛虫(鳞翅目枯叶蛾科)的潜在生物杀虫剂。在此篇研究中,我们分析了CyunNPV的基因组,并比较了它和其他Alpha属组I杆状病毒的基因组差异。454高通量测序结果显示:CyunNPV基因组全长为142,900bp,其中G+C含量为45%。生物信息学分析显示,其包含147个潜在的开放阅读框,其中包含38个杆状病毒核心基因,24个鳞翅目杆状病毒保守基因,9个组I杆状病毒保守基因,71个普通基因及5个特有基因。另外还包含13个同源重复区。系统进化分析显示CyunNPV位于Alpha属组I Clade a。不同于其他的组一杆状病毒,CyunNPV只包含组I杆状病毒11个独特型基因中的9个,它缺失了AC30ptp基因。在CyunNPV的F-like蛋白中,有两段连续的极性氨基酸的插入,分别位于融合肽及跨膜区的前端,可能会影响F-like蛋白融合功能,这可能是在杆状病毒进化过程中导致F-like蛋白失去融合活性的一个重要事件。以上发现显示CyunNPV是一种独特的Alpha属组I杆状病毒。
Letter

KIR2DL2/C1是中国1b型HCV感染及PEG-IFN和RBV联合治疗的不利因素

胡松, 袁发浒, 冯凌燕, 郑芳, 龚非力, 黄汉菊, 孙宾莲

2018, 33(4): 369 doi: 10.1007/s12250-018-0042-1

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自然杀伤细胞(NK cell)在丙肝病毒(HCV)感染中发挥着重要作用。杀伤性免疫球蛋白样受体(KIRs)是NK细胞表面的重要受体,它们可调控NK细胞的抗病毒功能。为了观察在中国汉族人群中KIR基因的出现频率与HCV感染以及治疗效果的差异,我们对333例HCV-1b感染者和320名健康人,以及在聚乙二醇α干扰素和利巴韦林联合治疗后追踪到的36名治疗无效者(NR)和62名效果明显者(SVR)进行基因检测分析。结果发现,HCV-1b感染者的KIR2DL2基因出现频率高于健康人。同时,与SVR组相比,NR组中KIR2DL2基因的出现频率也更高。进一步分析发现,在中国汉族人群中,KIR2DL2与其配体HLA-C1同时出现是HCV感染的危险因素,而且对HCV感染的治疗也具有负面影响。Meta分析也支持该结果,提示了KIR2DL2在清除HCV的过程中可能下调了NK细胞的杀伤能力,导致HCV的易感染性和对治疗的不敏感性,具体机制有待进一步研究。

我国猪群PCV3感染分子流行病学调查

李向东, 张超林, 乔明明, 郭江松, 邢广源, 晋春霞, 王娟, 孙明, 田克恭

2018, 33(4): 373 doi: 10.1007/s12250-018-0041-2

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本研究针对我国南部、中部和北部地区猪场采集的730份病猪临床样本, 用PCR方法检测猪圆环病毒3型(PCV3)DNA,结果表明PCV3阳性率为14.25%。成功获得的6个病毒基因组可被划分为3个不同分支。不同PCV3阳性样品的检出率依次为肺脏、淋巴结、死胎、肾脏、脑、扁桃、脾脏、心脏和肝脏。PCV2和PRRSV是PCV3混合感染的主要病原。上述结果表明PCV3已在我国广泛流行,其对养猪业潜在的危害应该给予足够的重视。

Serological Cross Reactivity between Zika and Dengue Viruses in Experimentally Infected Monkeys

2018, 33(4): 378 doi: 10.1007/s12250-018-0048-8

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In the absence of serum panels from individuals with absolute defined infection status, sera from experimentally infected monkeys were generated to cover all four infection scenarios with Zika or dengue virus alone as well as Zika infection followed by dengue and dengue infection followed by Zika. Our data indicated that no currently available single assay platform is sufficiently specific to serologically determine Zika positivity in the presence of prior exposure to dengue and vice versa.