VirologyPub Date : 2025-11-01Epub Date: 2025-08-21DOI: 10.1016/j.virol.2025.110661
Shinsuke Toba , Kentaro Uemura , Takao Sanaki , Shinji Kusakabe , Kei Konishi , Shigeru Miki , Yuki Maruyama , Atsuhiro Iimuro , Takao Shishido , Michihito Sasaki , Yasuko Orba , William W. Hall , Hirofumi Sawa , Akihiko Sato
{"title":"Synergistic antiviral activity of a cathepsin B/L inhibitor and a TMPRSS2 inhibitor against SARS-CoV-2 in vitro and in vivo","authors":"Shinsuke Toba , Kentaro Uemura , Takao Sanaki , Shinji Kusakabe , Kei Konishi , Shigeru Miki , Yuki Maruyama , Atsuhiro Iimuro , Takao Shishido , Michihito Sasaki , Yasuko Orba , William W. Hall , Hirofumi Sawa , Akihiko Sato","doi":"10.1016/j.virol.2025.110661","DOIUrl":"10.1016/j.virol.2025.110661","url":null,"abstract":"<div><div>The spike (S) protein of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) binds to a host cell receptor which dictates the viral entry pathway. SARS-CoV-2 utilizes two different pathways for cellular entry mediated by both a host type II transmembrane serine protease (TMPRSS2) and cathepsin proteases. These host proteases cleave the viral S protein and initiate membrane fusion allowing viral infection. We previously isolated a SARS-CoV-2 mutant with deletion in the furin cleavage site of the S gene (del2) and revealed differences in cell tropism between wild-type (WT) and del2 viruses. Here, we evaluated the antiviral activities of cellular protease inhibitors against SARS-CoV-2 WT and del2 viruses using several different cell lines. The TMPRSS2 inhibitor, camostat, exhibited strong antiviral activity against WT virus but not del2, while the cathepsin B/L inhibitor, K11777, exhibited potent antiviral activity against the del2 virus. We isolated K11777-escape mutants of SARS-CoV-2 and SARS-CoV and demonstrated that these mutations facilitated S protein cleavage at the S2′ site mediated by cathepsin L. Finally, we demonstrated that combination treatment of K11777 and camostat potently inhibited SARS-CoV-2 WT infection <em>in vitro</em> and <em>in vivo</em>, suggesting the usefulness of combination therapeutics targeting host TMPRSS2 and cathepsin proteases against coronavirus infection. In summary, our study characterized K11777 as an inhibitor of S2′ cleavage by cathepsins, highlighting the critical role of the S2’ site in SARS-CoV-2 cellular entry. This research sheds light on the infection process and has implications for potential therapeutic interventions for SARS-CoV-2 infection.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"612 ","pages":"Article 110661"},"PeriodicalIF":2.4,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144933827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A synonymous mutation in the preS2 region enhances production of infectious hepatitis B virus","authors":"Asako Murayama , Norie Yamada , Masaaki Toyama , Hussein Hassan Aly , Hironori Nishitsuji , Kunitada Shimotohno , Masanori Isogawa , Takanobu Kato","doi":"10.1016/j.virol.2025.110692","DOIUrl":"10.1016/j.virol.2025.110692","url":null,"abstract":"<div><h3>Background</h3><div>Hepatitis B virus (HBV) is classified into at least nine genotypes based on sequence heterogeneity. Clinical and virological characteristics vary among these genotypes, and differences have also been reported among strains within the same genotype. In this study, we aimed to clarify the strain-specific characteristics of patient-derived genotype C (GT-C) strains and identify a synonymous mutation responsible for these characteristics, along with the underlying mechanisms.</div></div><div><h3>Materials and methods</h3><div>HBV molecular clones were constructed from sequences obtained from two chronic hepatitis patients infected with GT-C. To evaluate HBsAg production and infectivity, these molecular clones were transfected into cell cultures, and the characteristics of the generated viruses were assessed. The HBV reporter virus was used to confirm these characteristics and determine the responsible regions. mRNA quantification and mRNA transfection experiments were performed to elucidate the mechanisms underlying high HBsAg production and enhanced infectivity.</div></div><div><h3>Results</h3><div>HBsAg production and infectivity were analyzed in two GT-C strains, GT-C1 and GT-C2. GT-C2 exhibited higher HBsAg production than GT-C1 did, whereas GT-C1 showed greater infectivity. Analysis of chimeric and mutated strains revealed that a synonymous mutation, a3210g, in the preS2 region was responsible for the high HBsAg production of GT-C2. Introducing this mutation into the GT-C1 strain led to increased HBsAg production due to increased HBsAg translation efficiency and further enhanced infectivity.</div></div><div><h3>Conclusions</h3><div>This HBV infection system with both high HBsAg production and high infectivity provides a valuable tool for studying HBV infection and propagation in cell culture and for developing antiviral strategies for HBV infection.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"612 ","pages":"Article 110692"},"PeriodicalIF":2.4,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145093371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Isolation, propagation, and characterization of a G9P[4] human rotavirus strain 543765 in Iran","authors":"Atefeh Kachooei , Reza Aramideh-Khouy , Mehrnaz Hosseini-Tehrani , Mahtab Mir-Hosseinian , Zahra Habib , Maryam Kazemi-Aghdam , Somayeh Jalivand , Tayebeh Latifi , Angila Ataei-Pirkooh , Zabihollah Shoja","doi":"10.1016/j.virol.2025.110695","DOIUrl":"10.1016/j.virol.2025.110695","url":null,"abstract":"<div><div>Group A rotavirus (RVA) is a leading etiological agent of diarrheal diseases in children less than 5 years of age. While live attenuated RV vaccines have demonstrated high efficacy in high-income countries (HICs), their performance is substantially reduced in low- and middle-income countries (LMICs). Despite this disparity, the development and evaluation of live attenuated RVA strains remain a central objective in RV vaccine research. In this study, a human RVA strain, designated 543765, was successfully isolated from a stool sample using MA104 cell culture. The isolate was characterized through observation of cytopathic effects (CPE), polyacrylamide gel electrophoresis (PAGE), reverse transcription-polymerase chain reaction (RT-PCR), hemagglutination assay, transmission electron microscopy (TEM), and complete genome sequencing. Genotypic analysis revealed the following constellation: G9-P[4]-I1 (Lineage IV/II recombinant)-R1-C1-M1-A1-N1-T1-E1-H1. These findings suggest that strain 543765 exhibits stable structural and replication properties, achieving titers of up to 10<sup>8</sup> TCID<sub>50</sub>/mL in MA104 cells. Given its genetic profile and in vitro growth characteristics, strain 543765 holds promise as a candidate for development into a monovalent vaccine capable of inducing both homotypic and heterotypic immune protection against G9P[4] and other RVA genotypes. However, further investigation is warranted to evaluate whether serial passages in cell culture have resulted in attenuation, a determination that requires validation through clinical studies.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"612 ","pages":"Article 110695"},"PeriodicalIF":2.4,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145093399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
VirologyPub Date : 2025-11-01Epub Date: 2025-09-01DOI: 10.1016/j.virol.2025.110674
Ki-Hye Kim , Hye Suk Hwang , Youri Lee , Yu-Jin Jung , Eun-Ju Ko , Jae Min Song , Sang-Moo Kang
{"title":"Interferon-γ receptor signaling is critical for balanced immune activation and protection against influenza after vaccination","authors":"Ki-Hye Kim , Hye Suk Hwang , Youri Lee , Yu-Jin Jung , Eun-Ju Ko , Jae Min Song , Sang-Moo Kang","doi":"10.1016/j.virol.2025.110674","DOIUrl":"10.1016/j.virol.2025.110674","url":null,"abstract":"<div><div>To better understand the contribution of interferon-γ (IFN-γ) receptor signaling to vaccine-induced immunity, we employed A129 (IFN-α/β receptor-deficient) and AG129 (IFN-α/β/γ receptor-deficient) mouse models. AG129 mice induced comparable levels of virus-specific IgG after vaccination with influenza virus H5 hemagglutinin (HA) virus-like particles (VLPs). Vaccinated AG129 mice with HA VLPs exhibited impaired Th1-immune responses, lower hemagglutination inhibition (HAI) titers, increased susceptibility to virus infection, and lower survival rates following influenza virus (H5N1) challenge than vaccinated A129 mice. The AG129 mice also displayed defective germinal center and plasma cell responses, dysregulated lung inflammation with elevated pro-inflammatory cytokines and chemokines, impaired recruitment of monocytes, natural killer cells, and antigen-presenting cells after HA VLP vaccination and virus challenge, compared to A129 mice. Collectively, these findings underscore the critical role of IFN-γ signaling in coordinating effective and balanced immune responses to influenza HA VLP vaccination and conferring protection against virus infection.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"612 ","pages":"Article 110674"},"PeriodicalIF":2.4,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145004951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A chiropteran factor of innate immunity can be recruited for rapid rescue and amplification of recombinant modified vaccinia Ankara (MVA)","authors":"Aurora Elhazaz Fernandez , Sirine Abidi , Karoline Mähl, Dominique Scheffler , Volker Sandig, Ingo Jordan","doi":"10.1016/j.virol.2025.110698","DOIUrl":"10.1016/j.virol.2025.110698","url":null,"abstract":"<div><div>Poxviruses are investigated as vectors for prophylactic and therapeutic vaccination. Transgenes are usually inserted via homologous recombination, and the desired vectors are isolated through sequential steps of plaque purification or limiting dilution. However, obtaining recombinants from the vast background of parental viruses is challenging for the ambitious timelines in personalised medicine and pandemic preparedness. We have developed a selection system based on tetherin from bats that eliminates parental viruses within the first passage after recombination. Tetherins are late-acting defensive factors that crosslink budding viruses to cellular membranes. Poxvirus morphogenesis is completed in the cytoplasm and only a subset of mature infectious particles acquires additional membranes from the trans-Golgi network. The outer of these membranes fuses with the plasma membrane for egress and is left behind. Tetherins have therefore not been suspected to interfere with release of poxviruses. We now describe that tetherin from the common vampire bat is as effective as tetherin from the Egyptian fruit bat and compare our results to conventional marker restoration based on a transiently deleted E3L gene. We demonstrate highly efficient simultaneous insertion of two transgenes into different positions of the genome of modified vaccinia Ankara (MVA) using the two tetherins. We furthermore show that recombination, rescue and amplification of vectors in suspension cultures in chemically-defined media is possible, a potential benefit for GMP campaigns. Observations with an EGFP fusion protein that is localised in the perinuclear space suggest that the bat tetherins may be active as a crosslinker during early steps of morphogenesis.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"612 ","pages":"Article 110698"},"PeriodicalIF":2.4,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145096526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
VirologyPub Date : 2025-11-01Epub Date: 2025-08-29DOI: 10.1016/j.virol.2025.110654
Shailesh D. Pawar , Deeksha S. Tare , Sachin S. Keng , Atul M. Walimbe , Vikas Sharma , Goldi Misra , Nisha Kurkure , Naveen Kumar
{"title":"Tracing the possible origins of the clade 2.3.4.4b highly pathogenic avian influenza H5Nx viruses from India","authors":"Shailesh D. Pawar , Deeksha S. Tare , Sachin S. Keng , Atul M. Walimbe , Vikas Sharma , Goldi Misra , Nisha Kurkure , Naveen Kumar","doi":"10.1016/j.virol.2025.110654","DOIUrl":"10.1016/j.virol.2025.110654","url":null,"abstract":"<div><div>Highly pathogenic avian influenza (HPAI) clade 2.3.4.4b H5Nx viruses are a major zoonotic concern. Clade 2.3.4.4b was first reported in India during the HPAI H5N8 outbreaks in zoological parks, in 2016. Recently, in June 2024, clade 2.3.4.4b HPAI H5N1 virus outbreaks were reported from Kerala. The genetic and molecular characterization of this H5N1 virus revealed that it is a novel reassortant comprising of internal genes derived from LPAI viruses reported from Kerala; and some of European origin. The exact spatio-temporal origins of these viruses were unknown. The present study was undertaken to trace the possible source of the clade 2.3.4.4b HPAI H5N1 and H5N8 viruses reported from India. Molecular clock and phylogeography analyses were carried out using BEAST v1.10.4 for the global and regional datasets of clade 2.3.4.4b H5Nx virus hemagglutinin gene sequences downloaded from the GISAID database. Preliminary phylogeography analysis using the global dataset revealed direct linkages of South Asia with the Middle East, North Africa, Japan, Korea, and China in the transmission network. Further analysis using regional datasets revealed that the H5N1 isolates reported from Kerala in 2024 had been introduced to India from East Asia, around 2022. The two reported H5N8 viruses from 2016 showed separate introductions from East Asian countries, including China and Japan respectively, around the year 2015. In the present study we report the spatio-temporal origins of clade 2.3.4.4b HPAI H5Nx viruses from South Asia. The analyses would be useful in furthering our understanding of this pathogen of human and animal health importance.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"612 ","pages":"Article 110654"},"PeriodicalIF":2.4,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145035039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Development of an effective DNA vaccine against ayu atypical cellular gill disease using draft genome information of the causative agent, Plecoglossus altivelis poxvirus","authors":"Shuntaro Baba , Tomoki Koyama , Daiki Komatsu , Tsubasa Uchino , Yuki Midorikawa , Yasunori Takano , Tatsuya Mori , Yuya Takagi , Shinpei Wada , Hidehiro Kondo , Megumi Matsumoto , Goshi Kato , Motohiko Sano","doi":"10.1016/j.virol.2025.110671","DOIUrl":"10.1016/j.virol.2025.110671","url":null,"abstract":"<div><div>Atypical cellular gill disease (ACGD) in ayu (<em>Plecoglossus altivelis</em>) caused by <em>P. altivelis</em> poxvirus (PaPV) infection has led to significant economic losses in Japanese aquaculture. The propagation of PaPV has not yet been successfully achieved in cultured cells. In this study, we sequenced a draft genome of PaPV and developed an effective vaccine against the disease based on this genomic information. The draft genome of PaPV, obtained from a diseased fish in 2016, was constructed using sequence data from an Illumina MiSeq analysis. The genome comprised 376,224 bp, including a 14,355 bp inverted terminal repeat at both ends, with a G + C content of 28.3 % and 353 predicted open reading frames (ORFs). Phylogenetic analysis using 13 core genes conserved across <em>Poxviridae</em> revealed that PaPV clusters with other fish poxviruses, including carp edema virus and salmon gill poxvirus, within the subfamily Chordopoxvirinae. The protective efficacy of a formalin-killed virus vaccine and DNA vaccines targeting ORF226 (vaccinia virus L1R homolog) and ORF227 (vaccinia virus D13L homolog) was evaluated. The DNA vaccine targeting ORF227 provided a high survival rate following virus challenge, whereas the formalin-killed vaccine resulted in lower survival. Gene expression analysis suggests that the effective DNA vaccine against ACGD likely induces cell-mediated immunity in the gills.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"612 ","pages":"Article 110671"},"PeriodicalIF":2.4,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144989454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Colloidal gold technology in viral diagnostics: Recent innovations, clinical applications, and future perspectives","authors":"Zhiyang He, Jingjing Zhang, Siping Kuang, Shuli Li, Yuxian Wang, Juntao Ding, Zhenghai Ma, Beibei Zhang","doi":"10.1016/j.virol.2025.110686","DOIUrl":"10.1016/j.virol.2025.110686","url":null,"abstract":"<div><div>Colloidal gold technology has revolutionized viral diagnostics through its rapid, cost-effective, and user-friendly applications, particularly in point-of-care testing (POCT). This review synthesizes recent advancements, focusing on its role in detecting respiratory viruses, hepatitis viruses, and emerging pathogens. The technology leverages the unique optical and physicochemical properties of gold nanoparticles (AuNPs), including localized surface plasmon resonance (LSPR) and high surface-to-volume ratios, to achieve rapid antigen-antibody recognition with visual readouts within 15 min. Innovations such as CRISPR-Cas-integrated lateral flow immunoassays (LFIAs), dual-mode plasmonic biosensors, and nanomaterials like CeO<sub>2</sub>-colloidal gold composites have enhanced sensitivity and multiplex capability, enabling simultaneous identification of co-circulating pathogens. Case studies highlight its efficacy in dengue serotyping, SARS-CoV-2 neutralizing antibody quantification, and HBV/HCV co-detection, demonstrating high clinical specificity. However, challenges persist, including the need for improved sensitivity; interference of sample matrix with immunity; false positives caused by cross-reactions; and limitations of semi-quantitative analysis. Recent progress in hybrid nanomaterial synthesis, surface functionalization, and device-level multiplexing—coupled with AI-driven data interpretation— promises to address these gaps. Future trends emphasize integration with surface-enhanced Raman scattering (SERS), microfluidics, and portable sensors to achieve sub-zeptomolar sensitivity and scalable deployment. By bridging nanotechnology with precision diagnostics, colloidal gold platforms are poised to redefine global viral surveillance, particularly in resource-limited settings, underscoring their indispensable role in pandemic preparedness.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"612 ","pages":"Article 110686"},"PeriodicalIF":2.4,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145010722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
VirologyPub Date : 2025-11-01Epub Date: 2025-08-28DOI: 10.1016/j.virol.2025.110670
Sanne L. Landman, Martijn J.W.E. Rabelink, Selas T.F. Bots, Yannick P.E. Lampo, Diana J.M. van den Wollenberg, Vera Kemp, Rob C. Hoeben
{"title":"A new adenovirus isolated from a western lowland gorilla held in captivity","authors":"Sanne L. Landman, Martijn J.W.E. Rabelink, Selas T.F. Bots, Yannick P.E. Lampo, Diana J.M. van den Wollenberg, Vera Kemp, Rob C. Hoeben","doi":"10.1016/j.virol.2025.110670","DOIUrl":"10.1016/j.virol.2025.110670","url":null,"abstract":"<div><div>Many adenovirus (AdV) species have been isolated from human and non-human primates. Here we describe the isolation of a new AdV from a western lowland gorilla held captive in a zoo. Analysis of the genome sequence demonstrated that this virus is a member of the Mastadenovirus genus, but markedly distinct from all previously described species. The new virus, AdV-lumc014, has a relatively low DNA sequence identity (<90 %) compared to other human and simian AdVs. The virus is most related to the HAdV-B and HAdV-E species, of which isolates were previously obtained from humans and apes (<em>i.e</em>. bonobos, chimpanzees, and western lowland gorillas). Phylogenetic analyses of the amino-acid sequences of the hexon, penton-base, fiber knob, protein IIIa, AdV polymerase, single-stranded DNA-binding protein, AdV protease, and protein IX confirmed the relationship with HAdV-B and HAdV-E. The phylogenetic distances exceed the value of 0.05 often used to separate distinct AdV species. In addition, we found evidence for recombination events between the AdV-lumc014 and HAdV-D. Almost no neutralizing immunity was detected in pooled human immunoglobulins, demonstrating that the virus is scarce or absent in the human population and that there is limited cross-reacting neutralizing immunity. This new AdV species may be a valuable expansion of the arsenal of AdVs that can be used for gene therapy, viral oncolysis, and as a vaccine carrier.</div></div>","PeriodicalId":23666,"journal":{"name":"Virology","volume":"612 ","pages":"Article 110670"},"PeriodicalIF":2.4,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144989467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}