Virus research最新文献

{"title":"Enhanced efficacy of Helicoverpa armigera nucleopolyhedrovirus against Spodoptera litura larvae using zeolite and chitosan nanoparticle formulations.","authors":"Mia Miranti, Iqbal Nur Iskandar, Melanie Melanie, Desak Made Malini, Camelia Panatarani, I Made Joni, Dedat Prismantoro, Febri Doni, Ravindra Chandra Joshi, Wawan Hermawan","doi":"10.1016/j.virusres.2025.199614","DOIUrl":"10.1016/j.virusres.2025.199614","url":null,"abstract":"<p><p>Helicoverpa armigera nucleopolyhedrovirus (HearNPV1) shows considerable potential as a sustainable biological control agent against insect pests. Enhancing its efficacy through formulation with appropriate carrier materials is critical for improving pest management strategies. This study evaluated the potential of chitosan and zeolite nanoparticles as delivery vehicles for HearNPV1, assessing their effects on mortality and lethal time in second-instar Spodoptera litura larvae. A single-factor randomized block design with three replications was used. The treatments consisted of HearNPV1 formulated with various concentrations (0.125 % to 0.5 %) of either chitosan or zeolite nanoparticles. Larval mortality and lethal time (LT) were recorded and analyzed using one-way ANOVA, with significant differences further assessed by Duncan's multiple range test (α=0.05). Results showed that formulating HearNPV1 with either chitosan or zeolite nanoparticles significantly increased larval mortality. Notably, even the lowest concentration tested (0.125 %) of both chitosan and zeolite nanoparticles achieved 66.67 % larval mortality within seven days post-infection. However, no significant differences in lethal time were observed among treatments, regardless of nanoparticle type or concentration. Larvae exposed to virus-nanoparticle formulations exhibited lethal times ranging from 3.0 to 4.67 days on average-similar to the duration observed in larvae infected with HearNPV1 alone. In conclusion, both chitosan and zeolite nanoparticles at 0.125 % concentrations effectively enhanced HearNPV1-induced mortality in S. litura larvae, although they did not shorten the time to death. These findings underscore the potential for nanoparticle-based HearNPV1 formulations to improve biological pest control, warranting further investigation into their practical application and mechanisms of action.</p>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":" ","pages":"199614"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12355152/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144795647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lesser-known non-apoptotic programmed cell death in viral infections.","authors":"Jiajun Wu, Xiaohan Qian, Shi Bai, Lijuan Wu, Xian Zhao","doi":"10.1016/j.virusres.2025.199612","DOIUrl":"10.1016/j.virusres.2025.199612","url":null,"abstract":"<p><p>Non-apoptotic programmed cell death (NAPCD) represents a diverse set of cell death mechanisms that differ from classical apoptosis and have recently gained attention in the context of viral infections. This review focuses on four key NAPCD types, including ferroptosis, cuproptosis, NETosis (neutrophil extracellular trap formation), and PANoptosis (a combination of pyroptosis, apoptosis, and necroptosis), and summarizes their distinct molecular pathways and roles during viral infections. We emphasize their functional relevance in SARS-CoV-2 infection, revealing how they significantly impact viral replication, host immune responses, and tissue damage. Furthermore, we explore the interaction between NAPCDs and specific immune responses. Specifically, ferroptosis influences macrophage polarization. Cuproptosis activates innate immunity via the cGAS-STING pathway. NETosis contributes to Th17 responses, and PANoptosis interacts with Th1, Th22, and Thαβ pathways. Understanding the interplay among these cell death pathways provides new insights into host-virus dynamics and uncovers potential therapeutic targets for viral diseases.</p>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":" ","pages":"199612"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12357283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144785382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization and antibody preparation of the gene products of grouper iridovirus ORF120L","authors":"Chu-Fan Cheng ,&nbsp;Hsiang-Chieh Chuang ,&nbsp;Yu-Shen Lai","doi":"10.1016/j.virusres.2025.199625","DOIUrl":"10.1016/j.virusres.2025.199625","url":null,"abstract":"<div><div>Grouper iridovirus (GIV) is regarded as a prominent viral pathogen of grouper, particularly during the larval and juvenile stages. The aim of this study was to comprehensively characterize the GIV-120L gene during viral infection. The results of sequence analysis suggest that GIV-120L is a 1,470 bp gene encoding a <em>Ranavirus</em>-specific viral protein. Recombinant GIV-120L protein was purified using a nickel-affinity column, and its molecular weight was found to be 59.1 kDa. To obtain antibodies against GIV, mice were immunized with recombinant GIV-120L protein, the spleen was harvested 8 weeks later, and hybridoma testing was performed using Sp2/0 myeloma cells. Polyclonal and monoclonal antibodies against GIV-120L were obtained. To characterize GIV-120L gene expression, grouper kidney (GK) cells were infected with GIV using cycloheximide (CHX) and cytosine arabinoside (AraC). GIV-120L transcripts and protein were found at 12–30 h post infection (hpi) and 18–30 hpi, respectively. In addition, inhibition with CHX and AraC confirmed that GIV-120L was a late gene. Immunofluorescence staining using the antibodies produced in the study confirmed that GIV-120L protein is expressed at viral assembly sites at 24 hpi. The findings of this study provide functional characterization of the GIV-120L viral gene, enhance understanding of GIV assembly, and offer insights for GIV diagnostic applications.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"360 ","pages":"Article 199625"},"PeriodicalIF":2.7,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144912258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single amino acid substitution at position 614 in SARS-CoV-2 Spike Protein alters viral assembly and infectivity","authors":"Xiaoshuang Shi ,&nbsp;Jiamin Wang ,&nbsp;Chang Li ,&nbsp;Shouwen Du","doi":"10.1016/j.virusres.2025.199624","DOIUrl":"10.1016/j.virusres.2025.199624","url":null,"abstract":"<div><div>The emergence of SARS-CoV-2 has posed a substantial global public - health threat and has led to the emergence of diverse variant strains. A prevalent mutation, D614G, is commonly detected in the spike glycoprotein (S) of successive SARS- CoV-2 variants, which enhances viral infectivity. Here, the objective was to examine the influence of mutations on the synthesis and processing of the S protein, virus assembly, and infectivity. This was achieved by artificially substituting the aspartic acid at position 614 of the S protein with 19 distinct amino acids, including glycine, via codon modification. Pseudoviruses and virus-like particles were employed as models for this investigation. The results demonstrated that the expression characteristics of the modified S proteins diverged from those of the original D614 variant. Moreover, pseudoviruses with various mutations displayed different efficiencies in entering cells expressing ACE2. Significantly, the D614P and D614C mutations disrupted the production and processing of the S protein, exerting a notable impact on virus assembly. However, co-immunoprecipitation analysis indicated that D614 mutations did not hinder the interaction between the S protein and the ACE2 receptor. These findings emphasize the significance of D614 or G614 in S protein expression and virus assembly, providing novel targets and perspectives for the progress of research on spike-based vaccines and antiviral therapeutics.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"360 ","pages":"Article 199624"},"PeriodicalIF":2.7,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144906910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of ebv-circRPMS1–p53 interaction in the proliferation and clinical progression of Epstein–Barr virus-associated gastric carcinoma","authors":"Ling Yang ,&nbsp;Meini Li ,&nbsp;Guiming Xie ,&nbsp;Xian Wu ,&nbsp;Mingxiong Qin ,&nbsp;Birong Guo ,&nbsp;Jingyue Zhang","doi":"10.1016/j.virusres.2025.199617","DOIUrl":"10.1016/j.virusres.2025.199617","url":null,"abstract":"<div><h3>Background</h3><div>Epstein–Barr virus-associated gastric carcinoma (EBVaGC) represents a distinct clinicopathological entity with unique molecular characteristics, including latent EBV infection and dysregulation of host tumor suppressors. However, the functional interplay between EBV circular RNAs (ebv-circRNAs) and p53 protein remains enigmatic. This study explored the role of ebv-circRPMS1, a previously uncharacterized ebv-circRNA, in EBVaGC pathogenesis.</div></div><div><h3>Methods</h3><div>To define ebv-circRPMS1–p53 interplay, siRNA knockdown (validated by RT-qPCR) modulated ebv-circRPMS1 in EBV+ cells. RIP/co-immunoprecipitation confirmed direct ebv-circRPMS1–p53 binding. EdU assays quantified proliferation. RNA-FISH/immunofluorescence mapped cytoplasmic colocalization. Xenografts evaluated in vivo tumorigenicity, while BaseScope/IHC analyzed tissues. Clinical cohort (<em>n</em> = 70) correlated co-expression with survival via Kaplan–Meier/Cox regression.</div></div><div><h3>Results</h3><div>This study demonstrated that ebv-circRPMS1 directly binds to p53, thereby enhancing tumor proliferation. Clinically, ebv-circRPMS1–p53 co-expression correlates with poor survival in EBVaGC patients.</div></div><div><h3>Conclusions</h3><div>These findings unveil a novel viral strategy for subverting host tumor suppression, providing a rationale for targeting the ebv-circRPMS1–p53 axis in precision oncology.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"360 ","pages":"Article 199617"},"PeriodicalIF":2.7,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144890619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Host factors and genetic polymorphisms influencing dengue infection","authors":"Mariam Ahmed Mehak,&nbsp;Mala Khan,&nbsp;Mamudul Hasan Razu","doi":"10.1016/j.virusres.2025.199623","DOIUrl":"10.1016/j.virusres.2025.199623","url":null,"abstract":"<div><div>The dengue virus (DENV) is a mosquito-borne pathogen that causes severe morbidity and between 50 and 100 million illnesses each year worldwide. About 25% of infected patients encounter severe forms of the disease, such as dengue hemorrhagic fever/dengue shock syndrome, which result in considerable rates of mortality and morbidity. The majority of instances of the disease appear as subclinical infection or mild fever. The pathophysiology of the unique dengue infection outcome is determined by the complex interplay of variables relating to the virus, vector, and host; the majority of this interaction is currently poorly understood. This review study will highlight the human genetic determinants of DENV vulnerability, including blood type, human leukocyte antigens, and single nucleotide polymorphisms in immune response genes associated with DENV illness. Other factors that influence the course of DENV susceptibility will also be discussed, including age, ethnicity, nutritional status and bleeding.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"360 ","pages":"Article 199623"},"PeriodicalIF":2.7,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144932839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional characteristics of endosymbiotic picornia-like virus in Diaphorina citri","authors":"Shuai Wang ,&nbsp;Muhammad Younas ,&nbsp;Chengtao Bao ,&nbsp;Yuxi Xiao ,&nbsp;Inzamam Ul Haq ,&nbsp;Jia Lü ,&nbsp;Yu Bin ,&nbsp;Taiyun Wei ,&nbsp;You Li","doi":"10.1016/j.virusres.2025.199619","DOIUrl":"10.1016/j.virusres.2025.199619","url":null,"abstract":"<div><div>The Asian citrus psyllid (<em>Diaphorina citri</em>) is the primary vector for <em>Candidatus</em> Liberibacter asiaticus (<em>C</em>Las), which is the causative agent of Huanglongbing (HLB). In recent years, increasing attention has been given to the endosymbiotic viruses harbored within <em>D. citri</em>, particularly Diaphorina citri picorna-like virus (DcPLV). However, the epidemiological distribution, biological effects, and role of DcPLV in pathogen transmission remain largely uncharacterized. This study investigates the field prevalence, transmission modes, and biological impacts of DcPLV in <em>D. citri</em> populations collected from 17 regions in China between 2023 and 2024. Detection of DcPLV revealed a widespread distribution, with an average infection rate of 35.18 %. Temporal monitoring in Gutian orchard further showed that DcPLV maintains consistently high infection levels throughout the year. The analysis of transmission showed that DcPLV is transmitted vertically from parents to offspring and horizontally from plant hosts. Biological assessments showed no significant effects of DcPLV on reproduction and adult longevity. Additionally, tissue-specific RT-qPCR revealed virus localization in the midgut and salivary glands, with viral accumulation progressively increasing during nymphal development and continuing into teneral adult. Furthermore, results demonstrated that DcPLV infection significantly enhanced <em>C</em>Las acquisition and accumulation in <em>D. citri,</em> which may contribute to increased vector competence. These findings provide novel insights on the interactions between DcPLV, the <em>D. citri</em>, and <em>C</em>Las.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"360 ","pages":"Article 199619"},"PeriodicalIF":2.7,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144875427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolutionary characterization and pathogenicity of Senecavirus isolated from Shandong, China","authors":"Yubei Dong ,&nbsp;Jiacheng Wen ,&nbsp;Chengyi Guo ,&nbsp;Jian Li ,&nbsp;Junfang Yan ,&nbsp;Minjing Li ,&nbsp;Ting Jiang ,&nbsp;Yanni Gao ,&nbsp;Xianwei Wang ,&nbsp;Ping Jiang ,&nbsp;Juan Bai","doi":"10.1016/j.virusres.2025.199618","DOIUrl":"10.1016/j.virusres.2025.199618","url":null,"abstract":"<div><div>Senecavirus A (SVA), previously called Seneca Valley virus, belongs to the family Picornaviridae, species Senecavirus A, in the Senecavirus genus. SVA infection causes vesicular lesions in sows and a sharp drop in neonatal piglet production. In this study, an SVA strain, SVA/SD/2023, was isolated from a pig farm in North China, and its genome was determined and analyzed. PCR, immunofluorescence, and western blotting revealed that the SVA/SD/2023 strain stably promoted the proliferation of BHK-21 cells. Electron microscopy showed that the purified virus was an icosahedral particle of approximately 27 nm in diameter. The 7286-nucleotide (not including the poly-A tail) genome of SVA/SD/2023 presented typical picornavirus features, including a single open reading frame of 5836 nucleotides encoding a 1604-amino-acid polyprotein.</div><div>The amino acid sequence of the SVA/SD/2023 strain was highly conserved (from 87.8% to 99.4% homology) with 47 reference strains isolated from different regions. Phylogenetic analyses revealed that the SVA/SD/2023 strain shared the highest sequence homology (99.4%) with the USA/IA46008/2015.</div><div>Animal regression tests revealed that infected animals demonstrated reduced appetite, fever, and depression, among other negative effects. SVA did not cause animal death. Increased Senecavirus A VP2 and neutralizing antibody levels were detected in the infected animals, and viral loads decreased with increasing antibody titers. Interestingly, the specific damage caused by viruses varied among different routes of infection. This study provides basic information for the subsequent exploration of SVA pathogenic mechanisms and disease progression.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"360 ","pages":"Article 199618"},"PeriodicalIF":2.7,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144875426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long noncoding RNA HNF4A-AS1 upregulates TLE4 to inhibit hepatitis B virus replication","authors":"Lihua Liu ,&nbsp;Wenxiu Dai ,&nbsp;Qinghui Wang ,&nbsp;Huizhong Qian ,&nbsp;Xiao Liu ,&nbsp;Qingqin Hao","doi":"10.1016/j.virusres.2025.199616","DOIUrl":"10.1016/j.virusres.2025.199616","url":null,"abstract":"<div><div>Emerging evidence has revealed that long noncoding RNAs (lncRNAs) are involved in hepatitis B virus (HBV) replication. However, the roles of most lncRNAs in HBV replication remain unclear. In the present study, we determined that HNF4A-AS1 was downregulated by HBV during infection. Interestingly, HNF4A-AS1 inhibited HBV transcription and replication in human hepatoma cells. Mechanistically, HNF4A-AS1 inhibited HBV replication by promoting TLE4 expression at the transcriptional level. The TLE4 WD-repeat domain is required for TLE4-mediated anti-HBV activity. Collectively, our findings have uncovered a negative feedback mechanism underlying HBV replication and HNF4A-AS1 expression and identify HNF4A-AS1 as a novel host restriction factor in HBV replication, providing a potential therapeutic target for HBV treatment.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"360 ","pages":"Article 199616"},"PeriodicalIF":2.7,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144859678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tecovirimat is active against various MPXV strains, while cidofovir, brincidofovir, trifluridine, and gemcitabine have no detectable MPXV-specific antiviral activity","authors":"Nobuyo Higashi-Kuwata ,&nbsp;Mariko Kato ,&nbsp;Shin-ichiro Hattori ,&nbsp;Yuki Takamatsu ,&nbsp;Hiroaki Mitsuya","doi":"10.1016/j.virusres.2025.199615","DOIUrl":"10.1016/j.virusres.2025.199615","url":null,"abstract":"<div><div>In treating patients with mpox, current treatment options are limited, with tecovirimat (TEC) being one of the few available. TEC has been approved by the European Medicines Agency (EMA) for treating patients with mpox and is in clinical use in Europe and Japan. However, following exposure to TEC, TEC-resistant variants such as A290V-containing variant (MPXV_R^TEC/A290V) emerge quickly. In such cases involving MPXV_R^TEC/A290V, alternative agents such as brincidofovir (BCV) have been used, although their efficacy remains controversial and their anti-MPXV activity is yet to be clearly defined. In the present work, we evaluated the anti-MPXV features of five agents (TEC; cidofovir, CDV; BCV; trifluridine, TFT; and gemcitabine, dFdC) reportedly active against various MPXV strains including MPXV^SPL2A7, MPXV^Zr-599, MPXV^Liberia and MPXV_R^TEC/A290V, employing cell-based quantitative assays using multiple target cell types such as VeroE6 cells as well as morphometric assays focusing on their cytostatic and cytotoxic natures. The EC₅₀ values of TEC against MPXV^SPL2A7, MPXV^Zr-599, and MPXV^Liberia were 0.001, 0.005, and 0.004 µM, respectively, without tangible cytotoxicity, while that against MPXV_R^TEC/A290V was ∼130-fold greater with 0.13 µM. The EC₅₀ values of CDV, BCV, TFT, and dFdC against MPXV_R^TEC/A290V were 18, 1.8, 3.8, and 0.02 µM, respectively; however, the apparent anti-MPXV activity of these four agents was highly associated with their cytotoxicity as they were examined with qualitative and quantitative cell-based-morphometric assays. The data strongly show that none the four agents examined exhibited significant anti-MPXV activity and indicate that effective anti-MPXV agents active against wild-type and drug-resistant variants are urgently needed.</div></div>","PeriodicalId":23483,"journal":{"name":"Virus research","volume":"360 ","pages":"Article 199615"},"PeriodicalIF":2.7,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144856506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}