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2016 Vol.31(5)

Serving the society since 1986. Throughout its 30-year history, Virologica Sinica has changed along with the development of virology, but what has remained constant is our close concerns and interactive connections in this field. This cover offers a look back at those classic and distinctive covers from the journal's history, featuring the milestones and special issues in the past 30 years. Standing at a new starting point, we will continue to serve as a platform for the communication and exchange of academic information and ideas in an international context. Be with us and look forward to the next 30 years.

Review

Three-dimensional cell culture models for investigating human viruses

Bing He, Guomin Chen, Yi Zeng

2016, 31(5): 363 doi: 10.1007/s12250-016-3889-z

Received: 09 October 2016 Accepted: 21 October 2016 Published: 27 October 2016
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Three-dimensional (3D) culture models are physiologically relevant, as they provide reproducible results, experimental flexibility and can be adapted for high-throughput experiments. Moreover, these models bridge the gap between traditional two-dimensional (2D) monolayer cultures and animal models. 3D culture systems have significantly advanced basic cell science and tissue engineering, especially in the fields of cell biology and physiology, stem cell research, regenerative medicine, cancer research, drug discovery, and gene and protein expression studies. In addition, 3D models can provide unique insight into bacteriology, virology, parasitology and host-pathogen interactions. This review summarizes and analyzes recent progress in human virological research with 3D cell culture models. We discuss viral growth, replication, proliferation, infection, virus-host interactions and antiviral drugs in 3D culture models.

Structure-function relationship of the mammarenavirus envelope glycoprotein

Wei Wang, Zheng Zhou, Leike Zhang, Shaobo Wang, Gengfu Xiao

2016, 31(5): 380 doi: 10.1007/s12250-016-3815-4

Received: 20 May 2016 Accepted: 27 June 2016 Published: 04 August 2016
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Mammarenaviruses, including lethal pathogens such as Lassa virus and Junín virus, can cause severe hemorrhagic fever in humans. Entry is a key step for virus infection, which starts with binding of the envelope glycoprotein (GP) to receptors on target cells and subsequent fusion of the virus with target cell membranes. The GP precursor is synthesized as a polypeptide, and maturation occurs by two cleavage events, yielding a tripartite GP complex (GPC) formed by a stable signal peptide (SSP), GP1 and GP2. The unique retained SSP interacts with GP2 and plays essential roles in virion maturation and infectivity. GP1 is responsible for binding to the cell receptor, and GP2 is a class I fusion protein. The native structure of the tripartite GPC is unknown. GPC is critical for the receptor binding, membrane fusion and neutralization antibody recognition. Elucidating the molecular mechanisms underlining the structure–function relationship of the three subunits is the key for understanding their function and can facilitate novel avenues for combating virus infections. This review summarizes the basic aspects and recent research of the structure–function relationship of the three subunits. We discuss the structural basis of the receptor-binding domain in GP1, the interaction between SSP and GP2 and its role in virion maturation and membrane fusion, as well as the mechanism by which glycosylation stabilizes the GPC structure and facilitates immune evasion. Understanding the molecular mechanisms involved in these aspects will contribute to the development of novel vaccines and treatment strategies against mammarenaviruses infection.

Manipulation of the host cell membrane by human γ-herpesviruses EBV and KSHV for pathogenesis

Fang Wei, Qing Zhu, Ling Ding, Qing Liang, Qiliang Cai

2016, 31(5): 395 doi: 10.1007/s12250-016-3817-2

Received: 26 May 2016 Accepted: 29 July 2016 Published: 12 September 2016
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The cell membrane regulates many physiological processes including cellular communication, homing and metabolism. It is therefore not surprising that the composition of the host cell membrane is manipulated by intracellular pathogens. Among these, the human oncogenic herpesviruses Epstein–Barr virus (EBV) and Kaposi’s sarcoma-associated herpesvirus (KSHV) exploit the host cell membrane to avoid immune surveillance and promote viral replication. Accumulating evidence has shown that both EBV and KSHV directly encode several similar membrane-associated proteins, including receptors and receptor-specific ligands (cytokines and chemokines), to increase virus fitness in spite of host antiviral immune responses. These proteins are expressed individually at different phases of the EBV/KSHV life cycle and employ various mechanisms to manipulate the host cell membrane. In recent decades, much effort has been made to address how these membrane-based signals contribute to viral tumorigenesis. In this review, we summarize and highlight the recent understanding of how EBV and KSHV similarly manipulate host cell membrane signals, particularly how remodeling of the cell membrane allows EBV and KSHV to avoid host antiviral immune responses and favors their latent and lytic infection.
Research Article

Ficolin-2 binds to HIV-1 gp120 and blocks viral infection

Fengling Luo, Tielong Chen, Jun Liu, Xihui Shen, Yinnan Zhao, Rongge Yang, Xiaolian Zhang

2016, 31(5): 406 doi: 10.1007/s12250-016-3808-3

Received: 13 May 2016 Accepted: 02 August 2016 Published: 29 August 2016
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Ficolin-2 is a lectin complement pathway activator present in normal human plasma and usually associated with infectious diseases, but little is known about the role of ficolin-2 in human immunodeficiency virus (HIV) infection. Here, we describe our novel findings that serum ficolin-2 concentrations of 103 HIV-1 patients were much higher compared to those of 57 healthy donors. In vitro analysis showed that HIV-1 infection could enhance ficolin-2 expression. We further demonstrated that recombinant ficolin-2 protein could bind with HIV-1 envelope glycoprotein gp120, and subsequently induce complement dependent cytotoxicity. Moreover, ficolin-2 could block the entry of HIV-1 into target cells (TZM-b1 and MT-2 cells) and infection in a ficolin-2 dosedependent manner. To our knowledge, this is the first report about the protective role of ficolin-2 against HIV-1 infection and our study suggests that ficolin-2 is an important human innate immune molecule against HIV.

Identification of interaction between HIV-1 glycoprotein 41 and integrase

Xiaowei Zhang, Fei Zhang, Xiaohe Ma, Xing Zhao, Wei Li, Zhiping Zhang, Jibin Zhang, Xian-En Zhang, Zongqiang Cui

2016, 31(5): 415 doi: 10.1007/s12250-016-3820-7

Received: 02 June 2016 Accepted: 30 August 2016 Published: 26 September 2016
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Human immunodeficiency virus-1 (HIV-1) encodes 15 viral proteins. Protein-protein interactions play a large role in the function of these proteins. In this study, we attempted to identify novel interactions between the HIV-1 proteins to better understand the role played by viral protein-protein interactions in the life cycle of HIV-1. Genes encoding the 15 viral proteins from the HIV-1 strain AD8 were inserted into the plasmids of a yeast two-hybrid system. By screening 120 pairs of proteins, interactions between seven pairs were found. This led to the discovery of an interaction between the HIV-1 proteins integrase (IN) and glycoprotein 41 (gp41), which was confirmed by both co-immunoprecipitation (Co-IP) assays and fluorescence resonance energy transfer (FRET) imaging in live cells. In addition, it was found that the amino acids at positions 76–100 of gp41 are required for it to bind to IN. Deletion of this region from gp41 prevented its interaction with IN and reduced the production of HIV-1 in 293T cells. This study provides new information on HIV-1 protein-protein interactions which improves the understanding of the biological functions of gp41 and IN during the virus life cycle.

De novo transcriptome analysis of Spodoptera exigua multiple nucleopolyhedrovirus (SeMNPV) genes in latently infected Se301 cells

Zheng Fang, Jingxu Shao, Qingbei Weng

2016, 31(5): 425 doi: 10.1007/s12250-016-3791-8

Received: 22 April 2016 Accepted: 22 September 2016 Published: 18 October 2016
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Cells of the P8-Se301-C1 strain are Spodoptera exigua cell clones that each harbor a partial version of the S. exigua multiple nucleopolyhedrovirus (SeMNPV) genome and which are resistant to homologous SeMNPV infections. The cells produce no viral progeny, suggesting that the infection is a latent-like viral infection. To investigate the SeMNPV genes harbored in the P8-Se301-C1 cells, the de novo transcriptomes of P8-Se301-C1 cells and S. exigua Se301 cells were analyzed and compared. A total of 54,569,296 reads were obtained from the P8-Se301-C1 cells that yielded 112,565 final unigenes with a mean length of 1,093 nt. A total of 56,865,504 reads were obtained from the Se301 cells that yielded 102,996 final unigenes with a mean length of 1,082 nt. Ten SeMNPV gene transcripts (se5, se7, se8, se12, se43, se45, se89, se90, se124, and se126) were detected in the P8-Se301-C1 cells by RNA-Seq but not in the Se301 cells, which was verified by RTPCR. 5'/3' RACE analyses showed that the 3'- or 5'-end sequences of the viral transcripts are aligned to the host gene sequences in P8-Se301-C1 cells, suggesting that the SeMNPV genes may integrate into and be transcribed with the host genes in the P8-Se301-C1 cells. Furthermore, six additional viral gene transcripts, se11, se42, se44, se88, se91, and se127 (incorporated into chimeric fusion transcripts in the P8-Se301-C1 cells), were detected in the RACE analyses. Taken together, sixteen SeMNPV transcripts were identified in the P8-Se301-C1 cell strain. This study provides information to develop the understanding of baculovirus latent infections and superinfection exclusion.
Letter

HPV18 DNA replication inactivates the early promoter P55 activity and prevents viral E6 expression

Xiaohong Wang, Haibin Liu, Hsu-Kun Wang, Craig Meyers, Louise Chow, Zhi-Ming Zheng

2016, 31(5): 437 doi: 10.1007/s12250-016-3887-1

Published: 25 October 2016
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HPV18 genome contains two major transcription start sites (TSS) respectively positioned at nt 55 (TSS-55 or promoter P55) and nt 102 (TSS-102 or promoter P102) in the early promoter region upstream of viral E6 open reading frame (ORF). The TATA box driving RNA transcription at the TSS-55 overlaps with a core region of the viral replication origin (Ori), whereas the TATA box for the TSS-102 is downstream and outside of the core Ori. In late stage of HPV18 infection or in highly differentiated keratinocytes, HPV18 DNA replication unwinds the TATA-containing Ori and prevents RNA transcription from the P55 promoter, but not from the P102 promoter. Because RNA transcripts derived from the P55 promoter, but not from the P102 promoter, bears a reasonable length (51 nts) of 5’ untranslational region (5’ UTR), we demonstrated that the P55-derived transcripts are responsible for viral E6 expression and thereby p53 stability. Inhibition of viral DNA replication by phosphonoacetic acid increases the P55 promoter transcription and viral E6 expression, subsequently leading to p53 reduction. Together, our data provide the first evidence that HPV18 DNA replication controls the expression of viral E6 expression from the P55 promoter.

Large discrepancy between the two-way rNHT distances in hemagglutinin-inhibition assay

Yousong Peng, Dayan Wang, Yuelong Shu, Taijiao Jiang

2016, 31(5): 441 doi: 10.1007/s12250-016-3802-9

Published: 09 August 2016
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Here, by collecting large amounts of HI data of seasonal influenza virus, i.e., influenza A(H1N1), A(H3N2) and B virus (Supplementary Materials), we systematically analyzed the relationship between the pairwise two-way rNHT distances for influenza viruses.

A quantitative RT-PCR assay for rapid detection of Eurasian lineage H10 subtype influenza A virus

Hailiang Sun, Jian-Li Xue, Elizabeth Bailey, Yifei Xu, Guoliang Hu, John Baroch, Yi Zhang, Lanny Pace, Thomas J DeLiberto, Xiu-Feng Wan

2016, 31(5): 444 doi: 10.1007/s12250-016-3826-1

Published: 18 September 2016
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Quantitative RT-PCR (qRT-PCR) has been commonly used for IAV detection in influenza surveillance and disease diagnosis because of its high sensitivity, specificity, and high throughput. A number of HA subtype specific qRT-PCR methods have been developed, including H5, H7, and H9 (Monne et al., 2008). However, there is still lack of a specific qRT-PCR method for detecting the emerging H10N8 IAVs. In this study, a Eurasian-lineage H10 specific qRT-PCR is developed and validated.
PERSPECTIVE

Pitfalls of restriction enzyme analysis in identifying, characterizing, typing, and naming viral pathogens in the era of whole genomedata, as illustrated by HAdV type 55

Qiwei Zhang, Shoaleh Dehghan, Donald Seto

2016, 31(5): 448 doi: 10.1007/s12250-016-3862-x

Published: 25 October 2016
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A recent controversy over the naming of a human adenovirus (HAdV) type 55 as type "11a" (Kajon et al., 2013; Walsh et al., 2010) serves as instructive example to illustrate some of the pitfalls of relying on REA to identify, characterize, type, and name adenoviral pathogens in the era of whole genome data. Some of these concerns have been addressed earlier specifically for adenovirus characterization, where it was noted REA is useful for "prototype-like restriction patterns" but "the occurrence of genome types with deviating restriction patterns limits the application of this method" (Wigand, 1987).

Import of Rift Valley fever to China: a potential new threat?

Xinliang Fu, Lifang Wang, Bo Fang, Ruirui Ma, Yun Zheng, San Huang, Pei Zhou, Zongxi Cao, Jin Tian, Shoujun Li, Guihong Zhang

2016, 31(5): 454 doi: 10.1007/s12250-016-3876-4

Published: 27 October 2016
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China has a large population, and its climate and the wide distribution of the mosquito vectors in south China are high risk factors for RVF outbreak. More importantly, once RVFV is introduced into permissive ecologies, it can become endemic, with the potential to spread into other non-endemic regions (Murithi et al., 2011). If there is an RVF outbreak in China, the disease may spread quickly to Southeast Asia and to other countries in Asia. Combined with the import of the Zika and yellow fever viruses this year (Su et al., 2016a; Wang L. et al., 2016), importation of arboviral pathogens poses a huge challenge for China. Therefore, all necessary measures should be taken to prevent and control RVF import and spread in China in the future.