Host cell cytoskeletons have been reported to have close contact with viruses during virus entry, intracellular transport, replication, and egress process. In this issue, Yue Zhang et al. provide a brief overview of the function of the most prominent flaviviruses-induced or -hijacked cytoskeletal structures including actin, microtubules and intermediate filaments, mainly focus on infection by dengue virus, Zika virus and West Nile virus. The cover image shows host actin cytoskeleton (green) with decorated myosin molecular motor (red) in human osteosarcoma cells (kindly provided by Prof. Yaming Jiu). See page 30–41 for details.
Tao Hu, Juan Li, Michael J. Carr, Sebastián Duchȇne and Weifeng Shi. The Asian Lineage of Zika Virus: Transmission and Evolution in Asia and the Americas[J]. Virologica Sinica, 2019, 34(1): 1-8. doi: 10.1007/s12250-018-0078-2.
Since first isolation in 1947 from the Zika forest in Uganda, Zika virus (ZIKV) has been principally known as a benign agent associated with sporadic human infections in a restricted number of African countries. However, during 2015–2016, an Asian lineage of ZIKV caused an unprecedentedly large outbreak in the Americas and sizeable numbers of exported cases across the globe. In this review, we critically appraise the recent advances in molecular epidemiological studies of ZIKV performed to date, and we highlight the pivotal role played by genomic surveillance in elucidating the origins, dissemination and evolution of the Asian lineage of ZIKV in Asia and in the Americas.
Huiqiang Wang and Yuhuan Li. Recent Progress on Functional Genomics Research of Enterovirus 71[J]. Virologica Sinica, 2019, 34(1): 9-21. doi: 10.1007/s12250-018-0071-9.
Enterovirus 71 (EV71) is one of the main pathogens that causes hand-foot-and-mouth disease (HFMD). HFMD caused by EV71 infection is mostly self-limited; however, some infections can cause severe neurological diseases, such as aseptic meningitis, brain stem encephalitis, and even death. There are still no effective clinical drugs used for the prevention and treatment of HFMD. Studying EV71 protein function is essential for elucidating the EV71 replication process and developing anti-EV71 drugs and vaccines. In this review, we summarized the recent progress in the studies of EV71 noncoding regions (5' UTR and 3' UTR) and all structural and nonstructural proteins, especially the key motifs involving in viral infection, replication, and immune regulation. This review will promote our understanding of EV71 virus replication and pathogenesis, and will facilitate the development of novel drugs or vaccines to treat EV71.
Jing Yang, Hong Wang and Wenyan Zhang. Regulation of Virus Replication and T Cell Homeostasis by N6-Methyladenosine[J]. Virologica Sinica, 2019, 34(1): 22-29. doi: 10.1007/s12250-018-0075-5.
RNA modifications are abundant in eukaryotes, bacteria, and archaea. N6-methyladenosine (m6A), a type of RNA modification mainly found in messenger RNA (mRNA), has significant effects on the metabolism and function of mRNAs. This modification is governed by three types of proteins, namely methyltransferases as "writers", demethylases as "erasers", and specific m6A-binding proteins (YTHDF1-3) as "readers". Further, it is important for the regulation of cell fate and has a critical function in many biological processes including virus replication, stem cell differentiation, and cancer development, and exerts its effect by controlling gene expression. Herein, we summarize recent advances in research on m6A in virus replication and T cell regulation, which is a rapidly emerging field that will facilitate the development of antiviral therapies and the study of innate immunity.
Yue Zhang, Wei Gao, Jian Li, Weihua Wu and Yaming Jiu. The Role of Host Cytoskeleton in Flavivirus Infection[J]. Virologica Sinica, 2019, 34(1): 30-41. doi: 10.1007/s12250-019-00086-4.
The family of flaviviruses is one of the most medically important groups of emerging arthropod-borne viruses. Host cell cytoskeletons have been reported to have close contact with flaviviruses during virus entry, intracellular transport, replication, and egress process, although many detailed mechanisms are still unclear. This article provides a brief overview of the function of the most prominent flaviviruses-induced or -hijacked cytoskeletal structures including actin, microtubules and intermediate filaments, mainly focus on infection by dengue virus, Zika virus and West Nile virus. We suggest that virus interaction with host cytoskeleton to be an interesting area of future research.
Jianhao Cao, Shuhong Luo and Yuanyan Xiong. The Variability of Amino Acid Sequences in Hepatitis B Virus[J]. Virologica Sinica, 2019, 34(1): 42-49. doi: 10.1007/s12250-018-0070-x.
Hepatitis B virus (HBV) is an important human pathogen belonging to the Hepadnaviridae family, Orthohepadnavirus genus. Over 240 million people are infected with HBV worldwide. The reverse transcription during its genome replication leads to low fidelity DNA synthesis, which is the source of variability in the viral proteins. To investigate the variability quantitatively, we retrieved amino acid sequences of 5, 167 records of all available HBV genotypes (A–J) from the Genbank database. The amino acid sequences encoded by the open reading frames (ORF) S/C/P/X in the HBV genome were extracted and subjected to alignment. We analyzed the variability of the lengths and the sequences of proteins as well as the frequencies of amino acids. It comprehensively characterized the variability and conservation of HBV proteins at the level of amino acids. Especially for the structural proteins, hepatitis B surface antigens (HBsAg), there are potential sites critical for virus assembly and immune recognition. Interestingly, the preS1 domains in HBsAg were variable at some positions of amino acid residues, which provides a potential mechanism of immune-escape for HBV, while the preS2 and S domains were conserved in the lengths of protein sequences. In the S domain, the cysteine residues and the secondary structures of the alpha-helix and beta-sheet were likely critical for the stable folding of all HBsAg components. Also, the preC domain and C-terminal domain of the core protein are highly conserved. However, the polymerases (HBpol) and the HBx were highly variable at the amino acid level. Our research provides a basis for understanding the conserved and important domains of HBV viral proteins, which could be potential targets for anti-virus therapy.
Xiangpeng Chen, Tianjiao Ji, Jiayun Guo, Wei Wang, Wenbo Xu and Zhengde Xie. Molecular Epidemiology of Echovirus 18 Circulating in Mainland China from 2015 to 2016[J]. Virologica Sinica, 2019, 34(1): 50-58. doi: 10.1007/s12250-018-0080-8.
Echovirus 18 (E18), a serotype of Enterovirus B (EV-B) species, is an important pathogen in aseptic meningitis. E18 had rarely been detected in mainland China, but became the predominant pathogen associated with viral encephalitis (VE) and meningitis in Hebei province for the first time in 2015. To investigate the molecular epidemiology and genetic characteristics of E18 in mainland China, sixteen E18 strains from patient throat swabs with hand, foot, and mouth disease (HFMD) in six provinces in China collected between 2015 and 2016, and four E18 strains isolated from 18 patient cerebrospinal fluid specimens with VE in Hebei Province in 2015 were obtained and sequenced. Combined with the sequences from the GenBank database, we performed an extensive genetic analysis. Phylogenetic analysis of VP1 gene sequences revealed that all E18 strains from mainland China after 2015 belonged to subgenotype C2. There were no obvious specific differences in phylogenetic and variation analyses of E18 genome sequences between HFMD and VE/meningitis strains. Potential multiple recombination may have occurred in the 50-untranslated region and in the P2 and P3 nonstructural protein-encoding regions of E18 strains from China. The current E18 strains were potential multiplerecombinant viruses. Overall, these findings supported that E18 caused HFMD, VE, and meningitis, although there were no significant associations between clinical features and viral genomic characteristics.
Jingyu Wang, Fan Wu, Chuntian Liu, Wenwen Dai, Yawei Teng, Weiheng Su, Wei Kong, Feng Gao, Linjun Cai, Ali Hou and Chunlai Jiang. Exosomes Released from Rabies Virus-Infected Cells May be Involved in the Infection Process[J]. Virologica Sinica, 2019, 34(1): 59-65. doi: 10.1007/s12250-019-00087-3.
Exosomes are cell-derived vesicles that are secreted by many eukaryotic cells. It has recently attracted attention as vehicles of intercellular communication. Virus-infected cells release exosomes, which contain viral proteins, RNA, and pathogenic molecules. However, the role of exosomes in virus infection process remains unclear and needs to be further investigated. In this study, we aimed to evaluate the effects of exosomes on rabies virus infection. OptiPrepTM density gradient centrifugation was used to isolate exosomes from rabies virus-infected cell culture supernatants. A rabies virus G protein enzyme-linked immunosorbent assay and acetylcholinesterase activity assays were performed to verify the centrifugation fractions. Exosomes were then characterized using transmission electron microscopy and Western blotting. Our results showed that rabies virus infection increased the release of exosomes. Treatment with GW4869 and si-Rab27a, two exosomal secretion inhibitors, inhibited exosome release. Furthermore, the inhibitors reduced the levels of extracellular and intracellular viral RNA. These data indicated that exosomes may participate in the viral infection process. Moreover, our results establish a basis for future research into the roles of exosomes in rabies virus infection and as potential targets for developing new antiviral strategies.
Juemin Xi, Fei Ye, Guanzhou Wang, Wei Han, Zhizhong Wei, Bin Yin, Jiangang Yuan, Boqin Qiang and Xiaozhong Peng. Polypyrimidine Tract-Binding Protein Regulates Enterovirus 71 Translation Through Interaction with the Internal Ribosomal Entry Site[J]. Virologica Sinica, 2019, 34(1): 66-67. doi: 10.1007/s12250-019-00089-1.
Enterovirus 71 (EV71), a major causative agent of hand, foot, and mouth disease, has caused periodic infection outbreaks in children in the Asia–Pacific region. In order to describe the largely unknown life cycle of EV71, the molecular basis of its virus-host interactions must first be determined. The 50 untranslated region of EV71 contains a cloverleaf-like structure and internal ribosomal entry site (IRES), which play an important role in transcription and translation of viral protein. We found that polypyrimidine tract-binding protein 1 (PTB) bound to the IRES of EV71. RNA recognition motifs 1 and 2 of PTB were responsible for its binding to the EV71 IRES. Moreover, PTB protein was shuttled from nucleus to cytoplasm after EV71 infection. Additionally, IRES activity and viral protein production were inhibited by PTB knockdown. These results suggest that PTB interacts with the EV71 IRES, and positively regulates viral protein translation.
Yanqin Ding, Na Li, Jinhan Sun, Linran Zhang, Jianhui Guo, Xueqi Hao and Yuning Sun. Oxymatrine Inhibits Bocavirus MVC Replication, Reduces Viral Gene Expression and Decreases Apoptosis Induced by Viral Infection[J]. Virologica Sinica, 2019, 34(1): 78-87. doi: 10.1007/s12250-019-00088-2.
Oxymatrine (OMT), as the main active component of Sophoraflavescens, exhibits a variety of pharmacological properties, including anti-oxidative, anti-inflammatory, anti-tumor, and anti-viral activities, and currently is extensively employed to treat viral hepatitis; however, its effects on parvovirus infection have yet to be reported. In the present study, we investigated the effects of OMT on cell viability, virus DNA replication, viral gene expression, cell cycle, and apoptosis in Walter Reed canine cells/3873D infected with minute virus of canines (MVC). OMT, at concentrations below 4 mmol/L(no cellular toxicity), was found to inhibit MVC DNA replication and reduce viral gene expression at both mRNA and protein levels, which was associated with the inhibition of cell cycle S-phase arrest in early-stage of MVC infection. Furthermore, OMT significantly increased cell viability, decreased MVC-infected cell apoptosis, and reduced the expression of activated caspase 3. Our results suggest that OMT has potential application in combating parvovirus infection.
Ziyang Sheng, Hui Chen, Kaihao Feng, Na Gao, Ran Wang, Peigang Wang, Dongying Fan and Jing An. Electroporation-Mediated Immunization of a Candidate DNA Vaccine Expressing Dengue Virus Serotype 4 prM-E Antigen Confers Long-Term Protection in Mice[J]. Virologica Sinica, 2019, 34(1): 88-96. doi: 10.1007/s12250-019-00090-8.
Dengue fever, caused by dengue viruses (DENVs), is a widespread mosquito-borne zoonotic disease; however, there is no available anti-dengue vaccine for worldwide use. In the current study, a DNA vaccine candidate (pV-D4ME) expressing prM-E protein of DENV serotype 4 (DENV-4) was constructed, and its immunogenicity and protection were evaluated in immunocompetent BALB/c mice. The pV-D4ME candidate vaccine induced effective humoral and cellular immunity of mice against DENV-4 in vivo when administered both at 50 μg and 5 μg through electroporation. Two weeks after receiving three immunizations, both doses of pV-D4ME DNA were shown to confer effective protection against lethal DENV-4 challenge. Notably, at 6 months after the three immunizations, 50 μg, but not 5 μg, of pV-D4ME could provide stable protection (100% survival rate) against DENV-4 lethal challenge without any obvious clinical signs. These results suggest that immunization with 50 μg pV-D4ME through electroporation could confer effective and long-term protection against DENV-4, offering a promising approach for development of a novel DNA vaccine against DENVs.
Liping Ma, Haizhou Liu, Runkun Wang, Tao Jin, Di Liu, George Fu Gao and Quanjiao Chen. Low Pathogenic Avian Influenza A (H5N7) Virus Isolated from a Domestic Duck in Dongting Lake Wetland of China, 2016[J]. Virologica Sinica, 2019, 34(1): 97-101. doi: 10.1007/s12250-018-0081-7.
Yuanyun Ao, Xiaolu Xie, Xiaogen Dong, Miao Jin and Zhaojun Duan. Genetic Analysis of an Emerging GII.P2–GII.2 Norovirus Associated with a 2016 Outbreak of Acute Gastroenteritis in China[J]. Virologica Sinica, 2019, 34(1): 111-114. doi: 10.1007/s12250-019-00084-6.