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2017 Vol.32(4)

How many different viruses are there on our planet? In the latest International Committee on Taxonomy of Viruses (ICTV) report, the list of named viruses has grown to 4404 species. What about unknown viruses? A study on estimating unknown viral diversity in Pteropus giganteus suggests that at least 320,000 different viruses infect mammals (5513 species). Following this method, there could be 100 million viruses in 1.7 million known species of animals, plants, insects and algae. When considering about viruses of bacteria, archaea, and other single-celled organisms, and viruses in less-studied biosphere (e.g. the ocean system), the number could be 1031. Just as the exploration of the Universe, scientists have never stopped taking efforts to further discover the viral universe and make a better life. On this issue’s cover, 3D-printed herpesvirus, adenovirus, poliovirus, hepatis B virus, and Zika virus (from left to right) are artistically presented in the vast space near the Leo constellation. 3D-printed viruses are courtesy of Dr. Ding Gao from the Core Facility of Wuhan Institute of Virology.

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Research Article

Influenza A virus-induced downregulation of miR-26a contributes to reduced IFNα/β production

Shijuan Gao, Jiandong Li, Liping Song, Jiaoxiang Wu, Wenlin Huang

2017, 32(4): 261 doi: 10.1007/s12250-017-4004-9

Received: 22 April 2017 Accepted: 21 June 2017 Published: 30 June 2017
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Innate immunity provides immediate defense against viral infection.Influenza A virus (IAV) is able to get past the first line of defense.Elucidation of the molecular interaction between influenza factors and the newly recognized host players in the innate response might help in our understanding of the root causes of virulence and pathogenicity of IAV.In this study,we show that expression of miR-26a leads to a significant inhibition of IAV replication.miR-26a does not directly target IAV genome.Instead,miR-26a activates the type I interferon (IFN) signaling pathway and promotes the production of IFN-stimulated genes,thus suppressing viral replication.Furthermore, ubiquitin-specific protease 3(USP3),a negative regulator of type I IFN pathway,is targeted by miR- 26a upon IAV challenge.However,miR-26a is significantly downregulated during IAV infection. Thus,downregulation of miR-26a is a new strategy evolved by IAV to counteract cellular antiviral responses.Our findings indicate that delivery of miR-26a may be a potential strategy for anti-IAV therapies.

Drug resistance mutation profiles of the drug-naïve and first-line regimen-treated HIV-1-infected population of Suzhou, China

Tingting Li, Feng Qian, Ting Yuan, Weilu Xu, Li Zhu, Jinlong Huang, Haiyan Wang, Yueping Zhu, Yinling Wang, Xiaohong Li, Saihong Gu, Zhuqing Tan, Hui Chen, Xiangrong Luo, Wei Zhu, Wenjuan Lu, Ping Xu, Ming Li, Yuying Chen, Yong Gao, Rongge Yang, Chuanwu Zhu, Binlian Sun

2017, 32(4): 271 doi: 10.1007/s12250-017-4002-y

Received: 19 April 2017 Accepted: 05 July 2017 Published: 07 August 2017
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Little is known about the prevalence of drug-resistant mutations in HIV-1-positive individuals in Suzhou,China.To elucidate the transmitted drug resistance (TDR) and acquired drug resistance mutation (ADR) profiles,we collected blood specimens from 127 drug-naïve and 117 first-line drugtreated HIV-1-infected individuals sampled from 2014 to 2016 in Suzhou.We successfully amplified pol fragments from 100 drug-naïve and 20 drug-treated samples.We then determined the drugresistant mutations to protease (PR) and reverse-transcriptase (RT) inhibitors according to the Stanford drug resistance database.Overall,11 and 13 individuals had transmitted (drug-naïve group) and acquired (treated group) resistance mutations,respectively.Six transmitted drugresistant mutations were found,including two mutations (L33F and L76V) in the protease region and four (K70N/E and V179D/E) in the RT region.Only L76V was a major mutation,and K70N/E and V179D/E are known to cause low-level resistance to RT inhibitors.All 13 treated participants who had major drug resistance mutations demonstrated intermediate to high resistance to efavirenz and nevirapine,and six had a treatment duration of less than three months.No major mutations to RT inhibitors were found,implying that the epidemic of transmitted resistance mutations was not significant in this area.Our results suggest that more frequent virus load and drug resistance mutation tests should be conducted for individuals receiving antiretroviral treatment,especially for newly treated patients.Our research provides insights into the occurrence of HIV-1 drug resistance in Suzhou and will help to optimize the treatment strategy for this population.

Human leukemia antigen-A*0201-restricted epitopes of human endogenous retrovirus W family envelope (HERV-W env) induce strong cytotoxic T lymphocyte responses

Xiaoning Tu, Shan Li, Lijuan Zhao, Ran Xiao, Xiuling Wang, Fan Zhu

2017, 32(4): 280 doi: 10.1007/s12250-017-3984-9

Received: 24 March 2017 Accepted: 20 July 2017 Published: 22 August 2017
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Human endogenous retrovirus W family (HERV-W) envelope (env) has been reported to be related to several human diseases,including autoimmune disorders,and it could activate innate immunity. However,there are no reports investigating whether human leukemia antigen (HLA)-A*0201+ restriction is involved in the immune response caused by HERV-W env in neuropsychiatric diseases.In the present study,HERV-W env-derived epitopes presented by HLA-A*0201 are described with the potential for use in adoptive immunotherapy.Five peptides displaying HLAA*0201-binding motifs were predicted using SYFEPITHI and BIMAS,and synthesized.A CCK-8 assay showed peptides W,Q and T promoted lymphocyte proliferation.Stimulation of peripheral blood mononuclear cells from HLA-A*0201+ donors with each of these peptides induced peptidespecific CD8+ T cells.High numbers of IFN-γ-secreting T cells were also detectable after several weekly stimulations with W,Q and T.Besides lysis of HERV-W env-loaded target cells,specific apoptosis was also observed.These data demonstrate that human T cells can be sensitized toward HERV-W env peptides (W,Q and T) and,moreover,pose a high killing potential toward HERV-W env-expressing U251 cells.In conclusion,peptides W Q and T,which are HERV-W env antigenic epitopes,have both antigenicity and immunogenicity,and can cause strong T cell immune responses.Our data strengthen the view that HERV-W env should be considered as an autoantigen that can induce autoimmunity in neuropsychiatric diseases,such as multiple sclerosis and schizophrenia.These data might provide an experimental foundation for a HERV-W env peptide vaccine and new insight into the treatment of neuropsychiatric diseases.

Detection and characterization of three zoonotic viruses in wild rodents and shrews from Shenzhen city, China

Bo Wang, Chun-Lin Cai, Bei Li, Wei Zhang, Yan Zhu, Wei-Hong Chen, Fei Zhuo, Zheng-Li Shi, Xing-Lou Yang

2017, 32(4): 290 doi: 10.1007/s12250-017-3973-z

Received: 10 March 2017 Accepted: 27 May 2017 Published: 17 July 2017
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Diverse species of rodents and shrews,which are abundant worldwide,harbor a variety of viruses; some of these are closely related to human viruses and possess zoonotic potential.Previously studies have demonstrated that the mammarenavirus and hantavirus carried by rodents or shrews could cause diseases in human population.To determine the distribution of zoonotic viruses in Shenzhen city,the major city in southern China with a high population density,we analyzed 225 rodents (Rattus norvegicus and Rattus flavipectus) and 196 shrews (Suncus murinus) from urban and rural districts for the presence of mammarenavirus,hantavirus,and hepatitis E virus (HEV) by RT-PCR targeting the conserved regions.The infection rates for mammarenavirus,hantaviruses, and HEV in rodents and shrews were 3.56%,6.89%,and 1.66%,respectively.Partial genome fragment analysis indicated that mammarenavirus and hantavirus strains had more than 90% and 99% nucleic acid identity with Cardamones virus and Seoul virus,respectively,which cause diseases in humans.Although the present HEV strains identified are typically found worldwide, phylogenetic analysis demonstrated a divergence of 16%.To our knowledge,the present work is the first report of the prevalence of mammarenavirus,hantaviruses,and rat HEV strains in rodents and shrews from Shenzhen city,China.Our findings highlight the zoonotic potential of rodent-and shrew-borne mammarenavirus and hantavirus,and the biodiversity of rat HEV isolates in Shenzhen city.The present work suggests that utilization of good hygiene habits is important to minimize the risk of zoonosis.

Coexistence of multiple genotypes of porcine epidemic diarrhea virus with novel mutant S genes in the Hubei Province of China in 2016

Zhe Zeng, Ting-Ting Li, Xin Jin, Fu-Hu Peng, Nian-Hua Song, Gui-Qing Peng, Xing-Yi Ge

2017, 32(4): 298 doi: 10.1007/s12250-017-4021-8

Received: 23 May 2017 Accepted: 05 July 2017 Published: 26 July 2017
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The emergence of highly virulent porcine epidemic diarrhea virus (PEDV) variants in China caused huge economic losses in 2010.Since then,large-scale sporadic outbreaks of PED caused by PEDV variants have occasionally occurred in China.However,the molecular diversity and epidemiology of PEDV in different provinces has not been completely understood.To determine the molecular diversity of PEDV in the Hubei Province of China,we collected 172 PED samples from 34 farms across the province in 2016 and performed reverse transcription polymerase chain reaction (RTPCR) by targeting the nucleocapsid (N) gene.Seventy-four samples were found to be PEDVpositive.We further characterized the complete spike (S) glycoprotein genes from the positive samples and found 21 different S genes with amino acid mutations.The PEDV isolates here presented most of the genotypes which were found previously in field isolates in East and SouthEast Asia,North America,and Europe.Besides the typical Genotypes I and II,the INDEX groups were also found.Importantly,58 new amino acids mutant sites in the S genes,including 44 sites in S1 and 14 sites in S2,were first described.Our results revealed that the S genes of PEDV showed variation and that diverse genotypes of PEDV coexisted and were responsible for the PED outbreaks in Hubei in 2016.This work highlighted the complexity of the epidemiology of PEDV and emphasized the need for reassessing the efficacy of classic PEDV vaccines against emerging variant strains and developing new vaccines to facilitate the prevention and control of PEDV in fields.

Evaluation of purified recombinant spike fragments for assessment of the presence of serum neutralizing antibodies against a variant strain of porcine epidemic diarrhea virus

Jianwei Hao, Yun Zhang, Shengkun Fang, Zhifen Wen, Xiangbin Zhang, Chunyi Xue, Yongchang Cao

2017, 32(4): 307 doi: 10.1007/s12250-017-3969-8

Received: 06 March 2017 Accepted: 14 June 2017 Published: 20 July 2017
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Since 2010,variant strains of porcine epidemic diarrhea virus (PEDV) have caused disasters in the pork industry.The spike (S) protein,as the major immunity-eliciting antigen,has previously been used for serological testing and has been found to correlate significantly with the results of the serum neutralization (SN) test.However,further evaluation of this method is needed as new epidemic strains of PEDV emerge.Hence,the main objective of this study was to assess sow sera and determine the correlation between enzyme-linked immunosorbent assay (ELISA) results (involving a newly isolated GDS01 virus-based ELISA and ELISAs based on seven recombinant fragments comprising overlapping S1 and partial S2 sequences) and SN titers.Furthermore,we determined the reliability of the ELISAs based on receiver operating characteristics (ROC) curve analyses.For the most promising ELISA,i.e.,the SP4 ELISA,the correlation coefficient (r) and the area under curve (AUC) were determined to be 0.6113 and 0.8538,respectively.In addition,we analyzed the homology of the SP4 sequences obtained from different strains (including vaccine strains) and found that various strains showed a high degree of homology in this region.Thus,we conclude that SP4 is a promising serological testing protein for use in the field.

Recombinant rabies virus expressing IL-15 enhances immunogenicity through promoting the activation of dendritic cells in mice

Tiange Chen, Yajing Zhang, Zhao Wang, Jie Yang, Mingming Li, Kunlun Wang, Min Cui, Zhen F. Fu, Ling Zhao, Ming Zhou

2017, 32(4): 317 doi: 10.1007/s12250-017-4036-1

Received: 19 June 2017 Accepted: 09 August 2017 Published: 29 August 2017
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Rabies remains a public health threat that kills approximately 59,000 people worldwide each year, most of which are from the developing countries of Africa and Asia where dog rabies are endemic. Therefore,developing an affordable and efficacious vaccine is crucial for rabies control in these countries.Interleukin (IL)-15,an immunoregulatory cytokine,is a pluripotent molecule with therapeutic potential,which targets many cell types and links the innate and adaptive immune system.In this study,IL-15 gene was cloned and inserted into the genome of a recombinant rabies virus (RABV) strain LBNSE (designated as LBNSE-IL15),and the effect of over-expression of IL-15 on the immunogenicity of RABV was investigated.It was found that mice vaccinated with LBNSEIL15 could induce significantly higher level of virus-neutralizing antibody (VNA) than those immunized with LBNSE,resulting in the higher protection after challenge.Further investigation was performed to find out the possible role of IL-15 plays in the process of antibody induction,and it was found that LBNSE-IL15 could enhance the maturation of dendritic cells (DCs) in immunized mice.Furthermore,the mice immunized with LBNSE-IL15 could promote the TFH cells differentiation and the generation of germinal center B cells and plasma cells.Together,these data indicated that IL-15 could be a potential adjuvant in enhancing the immunogenicity of RABV,contributing to the development of more-efficacious rabies vaccines.
Letter

Cypovirus capsid protein VP5 has nucleoside triphosphatase activity

Jie Yang, Qi Qian, Teng-Feng Li, Xueli Yang, Sok Jin Won, Xi Zhou

2017, 32(4): 328 doi: 10.1007/s12250-017-3999-2

Received: 14 April 2017 Accepted: 17 May 2017 Published: 26 May 2017
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As a major protein of cypovirus capsid shell,VP5 performs as the clamp protein to stabilize the capsid shell structure (Yu et al.,2008).And as a part of viral RNA (vRNA) replication machinery,VP5 has been found to possess an ATP-independent RNA chaperoning activity (Yang et al.,2014).Here,we report that VP5 also has the nucleoside triphosphatase (NTPase) activity,which can hydrolyze all kinds of NTPs and dNTPs.Thus,our finding reveals that VP5 is a multifunctional protein that may be involved in diverse processes during cypoviral life cycle.

A practical approach to generate suitable de novo synthesis RNA template for a flavivirus RNA-dependent RNA polymerase

Wei Shi, Peng Gong

2017, 32(4): 331 doi: 10.1007/s12250-017-4003-x

Received: 20 April 2017 Accepted: 19 May 2017 Published: 20 June 2017
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Taken together,we have successfully utilized the HDV ribozyme in the preparation of homogeneous RNA sample that may be free of sequence limitation at the 3'-end.To make the HDV approach-derived RNA suitable for directing de novo RNA synthesis by the WNV NS5 RdRP, the 2',3'-cyclic phosphate at its 3'-end needs to be removed. The cyclic phosphate interference with the WNV RdRP initiation is an interesting observation and the underlying mechanisms may deserve further investigation. The practical approach combining T7 RNAP transcription, HDV ribozyme self-cleavage,and T4 PNK 2',3'-cyclic phosphate removal utilized in this study is likely applicable for in vitro characterization of de novo viral RdRPs.In a broader context,this approach may be applicable for developing RNA-based assays and for X-ray crystallography-based or cryo-electron microscopy (EM)-based structural studies of RNA and RNA-protein complexes.

A convenient immunochromatographic test strip for rapid detection of Scylla serrata reovirus

Dongyang Fan, Jingwen Liu, Miaomiao Xu, Yangyang Yuan, Jifang Yang, Jigang Chen

2017, 32(4): 335 doi: 10.1007/s12250-017-4008-5

Received: 01 May 2017 Accepted: 06 June 2017 Published: 20 June 2017
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In the present study,we used polyclonal antibodies (pAb) raised against SsRV and monoclonal antibodies (mAb) specific for the SsRV capsid protein p29 to successfully develop a rapid and simple immunochromatographic strip for the facile detection of SsRV.

Host protein atlastin-1 promotes human immunodeficiency virus (HIV-1) replication

Wenyuan Shen, Bin Liu, Zhou Liu, Jiabin Feng, Chang Liu, Xiaohong Kong

2017, 32(4): 338 doi: 10.1007/s12250-017-3998-3

Received: 14 April 2017 Accepted: 05 July 2017 Published: 24 July 2017
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In conclusion,we first found that HIV infection upregulates the ATL1 mRNA.Up-regulation of ATL1 contributes to HIV-1 replication and down-regulation of ATL1 in host cells inhibited the viral replication.The further research found that ATL1 promoted the level of Env expression on the cell surface and then promoted the cell-to-cell fusion.Truncated mutation experiments revealed that the GTPase domain of ATL1 is the key domain of promoting Env-regulated cell-cell fusion.Finally, through the kinetic experiment,we found that ATL1 was able to promote long-term replication of HIV-1. We believe that the characterization of ATL1 contributes to a better understanding of HIV-host interactions and can identify potential novel antiviral targets.

Reconciling individual and population levels of porcine reproductive and respiratory syndrome virus evolution

Giovanni Franzo, Claudia Maria Tucciarone, Mattia Cecchinato, Michele Drigo

2017, 32(4): 342 doi: 10.1007/s12250-017-3981-z

Received: 20 March 2017 Accepted: 21 July 2017 Published: 07 August 2017
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In summary,the present study demonstrates that the forces favoring intra-animal diversification can cause the emergence of variants that,benefiting of their diversity at the population level,are able to succeed and spread in an often highly homogeneous environment,and to be further selected later.