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2017 Vol.32(3)

Human cytomegalovirus (HCMV) infection is a leading cause of birth defects, primarily affecting the central nervous system and causing its maldevelopment. Hes1, a downstream effector of Notch signaling pathway, plays an essential role on maintaining neural progenitor /stem cells (NPCs) cell fate and fetal brain development. In this issue, Xi-Juan Liu et al. reported the first observation of Hes1 oscillatory expression in human NPCs, and found HCMV infection disrupting the Hes1 rhythm and down-regulates its expression. The cover is adopted from a two-photon fluorescence image of Hes1 staining in NPCs (kindly provided by Xi-Juan Liu and Min-Hua Luo), and further processed with pseudo-color (in teal) at cytosol part. Like Hes1 rhythm, water lily also holds its own pattern of flowering rhythm. See page 188–198 for details.



An update: Epstein-Barr virus and immune evasion via microRNA regulation

Lielian Zuo, Wenxin Yue, Shujuan Du, Shuyu Xin, Jing Zhang, Lingzhi Liu, Guiyuan Li, Jianhong Lu

2017, 32(3): 175 doi: 10.1007/s12250-017-3996-5

Received: 08 April 2017 Accepted: 12 June 2017 Published: 26 June 2017
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Epstein-Barr virus (EBV) is an oncogenic virus that ubiquitously establishes life-long persistence in humans.To ensure its survival and maintain its B cell transformation function,EBV has developed powerful strategies to evade host immune responses.Emerging evidence has shown that microRNAs (miRNAs) are powerful regulators of the maintenance of cellular homeostasis.In this review,we summarize current progress on how EBV utilizes miRNAs for immune evasion.EBV encodes miRNAs targeting both viral and host genes involved in the immune response.The miRNAs are found in two gene clusters,and recent studies have demonstrated that lack of these clusters increases the CD4+ and CD8+ T cell response of infected cells.These reports strongly indicate that EBV miRNAs are critical for immune evasion.In addition,EBV is able to dysregulate the expression of a variety of host miRNAs,which influence multiple immune-related molecules and signaling pathways.The transport via exosomes of EBV-regulated miRNAs and viral proteins contributes to the construction and modification of the inflammatory tumor microenvironment. During EBV immune evasion,viral proteins,immune cells,chemokines,pro-inflammatory cytokines,and pro-apoptosis molecules are involved.Our increasing knowledge of the role of miRNAs in immune evasion will improve the understanding of EBV persistence and help to develop new treatments for EBV-associated cancers and other diseases.
Research Article

Human cytomegalovirus infection dysregulates neural progenitor cell fate by disrupting Hes1 rhythm and down-regulating its expression

Xi-Juan Liu, Xuan Jiang, Sheng-Nan Huang, Jin-Yan Sun, Fei Zhao, Wen-Bo Zeng, Min-Hua Luo

2017, 32(3): 188 doi: 10.1007/s12250-017-3956-0

Received: 16 February 2017 Accepted: 28 March 2017 Published: 24 April 2017
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Human cytomegalovirus (HCMV) infection is a leading cause of birth defects,primarily affecting the central nervous system and causing its maldevelopment.As the essential downstream effector of Notch signaling pathway,Hes1,and its dynamic expression,plays an essential role on maintaining neural progenitor/stem cells (NPCs) cell fate and fetal brain development.In the present study,we reported the first observation of Hes1 oscillatory expression in human NPCs,with an approximately 1.5 hour periodicity and a Hes1 protein half-life of about 17(17.6±0.2) minutes.HCMV infection disrupts the Hes1 rhythm and down-regulates its expression.Furthermore,we discovered that depleting Hes1 protein disturbed NPCs cell fate by suppressing NPCs proliferation and neurosphere formation,and driving NPCs abnormal differentiation.These results suggested a novel mechanism linking disruption of Hes1 rhythm and down-regulation of Hes1 expression to neurodevelopmental disorders caused by congenital HCMV infection.

Development of a reverse transcription quantitative polymerase chain reaction-based assay for broad coverage detection of African and Asian Zika virus lineages

Yang Yang, Gary Wong, Baoguo Ye, Shihua Li, Shanqin Li, Haixia Zheng, Qiang Wang, Mifang Liang, George F Gao, Lei Liu, Yingxia Liu, Yuhai Bi

2017, 32(3): 199 doi: 10.1007/s12250-017-3958-y

Received: 18 February 2017 Accepted: 26 April 2017 Published: 19 May 2017
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The Zika virus (ZIKV) is an arbovirus that has spread rapidly worldwide within recent times.There is accumulating evidence that associates ZIKV infections with Guillain-Barré Syndrome (GBS) and microcephaly in humans.The ZIKV is genetically diverse and can be separated into Asian and African lineages.A rapid,sensitive,and specific assay is needed for the detection of ZIKV across various pandemic regions.So far,the available primers and probes do not cover the genetic diversity and geographic distribution of all ZIKV strains.To this end,we have developed a one-step quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay based on conserved sequences in the ZIKV envelope (E) gene.The detection limit of the assay was determined to be five RNA transcript copies and 2.94×10-3 50% tissue culture infectious doses (TCID50) of live ZIKV per reaction.The assay was highly specific and able to detect five different ZIKV strains covering the Asian and African lineages without nonspecific amplification,when tested against other flaviviruses.The assay was also successful in testing for ZIKV in clinical samples.Our assay represents an improvement over the current methods available for the detection ZIKV and would be valuable as a diagnostic tool in various pandemic regions.

Rabies virus co-localizes with early (Rab5) and late (Rab7) endosomal proteins in neuronal and SH-SY5Y cells

Waqas Ahmad, Yingying Li, Yidi Guo, Xinyu Wang, Ming Duan, Zhenhong Guan, Zengshan Liu, Maolin Zhang

2017, 32(3): 207 doi: 10.1007/s12250-017-3968-9

Received: 04 March 2017 Accepted: 09 May 2017 Published: 16 June 2017
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Rabies virus (RABV) is a highly neurotropic virus that follows clathrin-mediated endocytosis and pH-dependent pathway for trafficking and invasion into endothelial cells.Early (Rab5,EEA1) and late (Rab7,LAMP1) endosomal proteins play critical roles in endosomal sorting,maturity and targeting various molecular cargoes,but their precise functions in the early stage of RABV neuronal infection remain elusive.In this study,the relationship between enigmatic entry of RABV with these endosomal proteins into neuronal and SH-SY5Y cells was investigated. Immunofluorescence,TCID50 titers,electron microscopy and western blotting were carried out to determine the molecular interaction of the nucleoprotein (N) of RABV with early or late endosomal proteins in these cell lines.The expression of N was also determined by down-regulating Rab5 and Rab7 in both cell lines through RNA interference.The results were indicative that N proficiently colocalized with Rab5/EEA1 and Rab7/LAMP1 in both cell lines at 24 and 48 h post-infection,while N titers significantly decreased in early infection of RABV.Down-regulation of Rab5 and Rab7 did not inhibit N expression,but it prevented productive infection via blocking the normal trafficking of RABV in a low pH environment.Ultrathin sections of cells studied by electron microscope also verified the close association of RABV with Rab5 and Rab7 in neurons.From the data it was concluded that primary entry of RABV strongly correlates with the kinetics of Rab-proteins present on early and late vesicles,which provides helpful clues to explain the early events of RABV in nerve cells.

Human endogenous retrovirus W env increases nitric oxide production and enhances the migration ability of microglia by regulating the expression of inducible nitric oxide synthase

Ran Xiao, Shan Li, Qian Cao, Xiuling Wang, Qiujin Yan, Xiaoning Tu, Ying Zhu, Fan Zhu

2017, 32(3): 216 doi: 10.1007/s12250-017-3997-4

Received: 13 April 2017 Accepted: 26 May 2017 Published: 23 June 2017
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Human endogenous retrovirus W env (HERV-W env) plays a critical role in many neuropsychological diseases such as schizophrenia and multiple sclerosis (MS).These diseases are accompanied by immunological reactions in the central nervous system (CNS).Microglia are important immunocytes in brain inflammation that can produce a gasotransmitter-nitric oxide (NO).NO not only plays a role in the function of neuronal cells but also participates in the pathogenesis of various neuropsychological diseases.In this study,we reported increased NO production in CHME-5 microglia cells after they were transfected with HERV-W env.Moreover,HERV-W env increased the expression and function of human inducible nitric oxide synthase (hiNOS) and enhanced the promoter activity of hiNOS.Microglial migration was also enhanced.These data revealed that HERV-W env might contribute to increase NO production and microglial migration ability in neuropsychological disorders by regulating the expression of inducible NOS.Results from this study might lead to the identification of novel targets for the treatment of neuropsychological diseases,including neuroinflammatory diseases,stroke,and neurodegenerative diseases.

Detection of diverse viruses in alimentary specimens of bats in Macau

Jie Liang, Xing-Lou Yang, Bei Li, Qi Liu, Qin Zhang, Hui Liu, Hon-Pio Kan, Kai-Chin Wong, Si-Nga Chek, Xiangyang He, Xingwen Peng, Zheng-Li Shi, Yi Wu, Libiao Zhang

2017, 32(3): 226 doi: 10.1007/s12250-017-3976-9

Received: 12 March 2017 Accepted: 09 May 2017 Published: 01 June 2017
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Bats carry a variety of viruses,and some of them cause public health problems.Macau,which is famous for its gambling industry,has a complex population structure.The globalization in such an international metropolis has enhanced the chance of disease transmission.Therefore,surveillance of zoonotic viruses is necessary for the early warning of potential emerging infectious diseases. Here,we report the first surveillance of bat viruses in Macau.In this study,we collected 1004 samples involving 10 bat species from 7 sites from April 2015 to May 2016,and examined the presence of viruses using nucleic acid-based methods.Coronaviruses,adenoviruses and paramyxoviruses were detected in these samples,with a high prevalence of coronaviruses.While, none was positive for hepatitis A virus,hepatitis E virus or hantavirus.Co-infections are not common in those bat species,but coronavirus HKU6 and adenovirus can be found commonly occurred in Myotis ricketti.

Phylogenetic analysis based on mitochondrial DNA sequences of wild rats, and the relationship with Seoul virus infection in Hubei, China

Dong-Ying Liu, Jing Liu, Bing-Yu Liu, Yuan-Yuan Liu, Hai-Rong Xiong, Wei Hou, Zhan-Qiu Yang

2017, 32(3): 235 doi: 10.1007/s12250-016-3940-0

Received: 29 December 2016 Accepted: 01 June 2017 Published: 26 June 2017
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Seoul virus (SEOV),which is predominantly carried by Rattus norvegicus,is one of the major causes of hemorrhagic fever with renal syndrome (HFRS) in China.Hubei province,located in the central south of China,has experienced some of the most severe epidemics of HFRS.To investigate the mitochondrial DNA (mtDNA)-based phylogenetics of wild rats in Hubei,and the relationship with SEOV infection,664 wild rats were captured from five trapping sites in Hubei from 2000-2009 and 2014-2015.Using reverse-transcription (RT)-PCR,41(6.17%) rats were found to be positive for SEOV infection.The SEOV-positive percentage in Yichang was significantly lower than that in other areas.The mtDNA D-loop and cytochrome b (cyt-b) genes of 103 rats were sequenced. Among these animals,37 were SEOV-positive.The reconstruction of the phylogenetic relationship (based on the complete D-loop and cyt-b sequences) allowed the rats to be categorized into two lineages,R.norvegicus and Rattus nitidus,with the former including the majority of the rats.For both the D-loop and cyt-b genes,18 haplotypes were identified.The geographic distributions of the different haplotypes were significantly different.There were no significant differences in the SEOVpositive percentages between different haplotypes.There were three sub-lineages for the D-loop, and two for cyt-b.The SEOV-positive percentages for each of the sub-lineages did not significantly differ.This indicates that the SEOV-positive percentage is not related to the mtDNA D-loop or cyt-b haplotype or the sub-lineage of rats from Hubei.

Retromer localizes to autophagosomes during HCV replication

Peiqi Yin, Zhi Hong, Leiliang Zhang, Youyang Ke

2017, 32(3): 245 doi: 10.1007/s12250-016-3914-2

Published: 13 April 2017
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In summary, we propose a model for the role of retromer in HCV replication. Upon HCV infection, retromer may provide double-membrane autophagosomal membranes for HCV replication. Our studies suggested a novel link between retromer and autophagy in HCV replication, which may provide new therapeutic targets for antiviral therapy.

Molecular typing of non-polio enteroviruses isolated from acute flaccid paralysis cases in Iran from 2010 to 2015

Ahmad Nejati, Mohammad Farahmand, Hamideh Tabatabaie, Maryam Yousefi, Yaghoob Mollaei-Kandelous, Shohreh Shahmahmoodi

2017, 32(3): 249 doi: 10.1007/s12250-017-3945-3

Published: 05 June 2017
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In summary, our findings showed that for correct identification of NPEVs, cell lines other than RD cells must be used. In addition, neutralization tests did not show high sensitivity for identification of all NPEVs. Finally, establishment of direct molecular tests with high sensitivity and specificity is needed to identify NPEV from patient and environmental samples.

Isolation and phylogenetic study of Rift Valley fever virus from the first imported case to China

Yongxia Shi, Kui Zheng, Xiaobo Li, Liqiang Li, Shufen Li, Jinmin Ma, Jun Dai, Jingkai Ji, Shuai Yuan, Haorong Lu, Jiandong Li, Fangfang Sun, Xun Xu, Jicheng Huang

2017, 32(3): 253 doi: 10.1007/s12250-017-3949-z

Received: 22 January 2017 Accepted: 12 April 2017 Published: 02 May 2017
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Here, laboratory detection, virus isolation, whole genome sequencing and phylogenetic analysis were performed to characterize the first imported case of Rift Valley fever virus infection returning from Angola.

CD95-CD95L interaction mediates the growth control of MHV68 immortalized B cells by cytotoxic T cells

Sihan Dong, Lingbing Tan, Guifang Chen, Xiaozhen Liang

2017, 32(3): 257 doi: 10.1007/s12250-017-3971-1

Received: 09 March 2017 Accepted: 26 April 2017 Published: 15 May 2017
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In conclusion, our current data demonstrate that MHV68-immortalized SL-1 cells can be recognized and controlled by specific cytotoxic T cells through CD95/CD95L-mediated apoptosis. This is in agreement with that CD4 T cells control the growth of EBV-infected cells through CD95/CD95L-mediated apoptosis, which suggests that the growth control of gammaherpesvirus-associated lymphoma cells by cytotoxic T cell shares conserved mechanism.