Viruses-Basel最新文献

{"title":"A Mycovirus Representing a Novel Lineage and a Mitovirus of <i>Botrytis cinerea</i> Co-Infect a Basidiomycetous Fungus, <i>Schizophyllum commune</i>.","authors":"Jie Duan, Anmeng Zhang, Yanping Fu, Yang Lin, Jiatao Xie, Jiasen Cheng, Tao Chen, Bo Li, Xiao Yu, Xueliang Lyu, Daohong Jiang","doi":"10.3390/v16111767","DOIUrl":"10.3390/v16111767","url":null,"abstract":"<p><p>Strain IBc-114 was isolated from a gray mold lesion and was identified as the fungus <i>Schizophyllum commune.</i> In this strain, two mycoviruses, Schizophyllum commune RNA virus 1 (ScRV1, C_AA053475.1) and Botrytis cinerea mitovirus 9 strain IBc-114 (BcMV9/IBc-114, C_AA053476.1), were isolated and characterized. ScRV1 has flexuous filamentous particles about 20 ± 2.1 nm in diameter and 1000 ± 94.2 nm in length. The genome of ScRV1 is 7370 nt in length and contains two open reading frames (ORFs) which encode a polyprotein and a coat protein, respectively. The polyprotein has 1967 aa, including a helicase domain and an RdRp domain which has the highest identity of 28.21% with that of Entomophthora benyvirus E (EbVE). The coat protein has 241 aa which is mostly phylogenetically close to the coat proteins of <i>Alphatetraviridae</i>. Based on the phylogenetic analysis of ScRV1 and viruses selected, ScRV1 might represent a new family (temporarily named Mycobenyviridae) of the order <i>Hepelivirales</i>. The genome of BcMV9/IBc-114 that infects <i>S. commune</i> is 2729 nt in length and has only one ORF encoding an RdRp protein with 719 aa. BcMV9/IBc-114 has the highest identity of 98.61% with Botrytis cinerea mitovirus 9 (BcMV9) (MT089704). ScRV1, but not BcMV9/IBc-114, has certain effects on the host growth of <i>S. commune</i>. Furthermore, BcMV9/IBc-114 has been demonstrated to replicate in the ascomycetous fungi <i>Botrytis cinerea</i> and <i>Sclerotinia sclerotiorum</i>, and it negatively affects the growth and pathogenicity of <i>B. cinerea</i>, but it does not affect <i>S. sclerotiorum</i>. This is the first report of mycoviruses in <i>S. commune</i> and cross-phyla transmission of mitovirus in nature.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"16 11","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11598958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142733957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Transcriptional Program of <i>Staphylococcus aureus</i> Phage K Is Affected by a Host <i>rpoC</i> Mutation That Confers Phage K Resistance.","authors":"Rohit Kongari, Melissa D Ray, Susan M Lehman, Roger D Plaut, Deborah M Hinton, Scott Stibitz","doi":"10.3390/v16111773","DOIUrl":"10.3390/v16111773","url":null,"abstract":"<p><p>To better understand host-phage interactions and the genetic bases of phage resistance in a model system relevant to potential phage therapy, we isolated several spontaneous mutants of the USA300 <i>S. aureus</i> clinical isolate NRS384 that were resistant to phage K. Six of these had a single missense mutation in the host <i>rpoC</i> gene, which encodes the RNA polymerase β' subunit. To examine the hypothesis that mutations in the host RNA polymerase affect the transcription of phage genes, we performed RNA-seq analysis on total RNA samples collected from NRS384 wild-type (WT) and <i>rpoC</i>_G17D mutant cultures infected with phage K, at different timepoints after infection. Infection of the WT host led to a steady increase of phage transcription relative to the host. Our analysis allowed us to define 53 transcriptional units and to categorize genes based on their temporal expression patterns. Predicted promoter sequences defined by conserved -35, -10, and, in some cases, extended -10 elements, were found upstream of early and middle genes. However, in many cases, sequences upstream of late genes did not contain clear, complete, canonical promoter sequences, suggesting that factors in addition to host RNA polymerase are required for their expression. Infection of the <i>rpoC</i>_G17D mutant host led to a transcriptional pattern that was similar to that of the WT at early timepoints. However, beginning at 20 min after infection, transcription of late genes (such as phage structural genes and host lysis genes) was severely reduced. Our data indicate that the <i>rpoC</i>_G17D mutation prevents the expression of phage late genes, resulting in a failed infection cycle for phage K. In addition to illuminating the global transcriptional landscape of phage K throughout the infection cycle, this study will inform our investigations into the basis of phage K's control of its transcriptional program as well as mechanisms of phage resistance.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"16 11","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11598898/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142734181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Thermal Stability of Influenza Viruses in Milk.","authors":"Wanke Hu, Zhao Wang, Yunxia Chen, Siyu Wu, Tianyu Li, Shao-Lun Zhai, Xianghong Ju, Yipeng Sun, Wen-Kang Wei, Jieshi Yu","doi":"10.3390/v16111766","DOIUrl":"10.3390/v16111766","url":null,"abstract":"<p><p>Highly pathogenic avian influenza viruses (HPAIVs) of the H5N1 subtype (clade 2.3.4.4b) have been detected in raw milk from infected cows. Several studies have examined the time and temperature parameters to ascertain whether influenza viruses in milk can be inactivated completely under commercial pasteurization conditions, yielding conflicting results. This study aimed to investigate whether milk could help protect influenza viruses from heat treatment. After heat treatment at 49 °C for one hour, the titer reduction of the influenza A/WSN/1933 (A/H1) virus in milk was approximately 1.6 log₁₀TCID₅₀/mL, which was significantly lower than that (3 log₁₀TCID₅₀/mL) observed in the Dulbecco's Modified Eagle Medium (DMEM) control media. The influenza D/bovine/CHN/JY3002/2022 (D/Yama2019) virus in milk retained a high residual infectivity (4.68 × 10³ log10TCID₅₀/mL) after treatment at 53 °C; however, the virus in DMEM completely lost its infectivity under the same conditions. Moreover, the influenza A/chicken/CHN/Cangzhou03/2023 (A/H5) virus in DMEM could be inactivated completely using any of the three heat treatment methods: 63 °C for 30 min, 72 °C for 15 s, or 80 °C for 15 s. For the virus present in milk, only heat treatment at 80 °C for 15 s completely inactivated it. These results suggest that milk prevents influenza viruses from pasteurization inactivation.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"16 11","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11598856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142734256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PLNC8 αβ Potently Inhibits the Flavivirus Kunjin and Modulates Inflammatory and Intracellular Signaling Responses of Alveolar Epithelial Cells.","authors":"Abubakr A M Omer, Sanjiv Kumar, Bo Söderquist, Wessam Melik, Torbjörn Bengtsson, Hazem Khalaf","doi":"10.3390/v16111770","DOIUrl":"10.3390/v16111770","url":null,"abstract":"<p><p>PLNC8 αβ is a cationic antimicrobial peptide that previously has been reported to express both antibacterial and antiviral properties. This study aimed to further elucidate the antiviral effects of PLNC8 αβ and its impact on virus-induced cytotoxicity and inflammatory signaling in human alveolar epithelial cells (A549) infected with the flavivirus Kunjin. Complementary in silico analyses using molecular dynamics (MD) simulation were conducted to investigate the mechanism of action of PLNC8 αβ by studying the interaction of PLNC8 α and β with models of a flavivirus membrane and a eukaryotic plasma membrane, respectively. Our findings demonstrated that PLNC8 αβ significantly reduces both extracellular and intracellular viral loads, as confirmed by plaque reduction assays and RT-PCR. The peptide also mitigated virus-induced cytotoxicity and inflammation. Notably, PLNC8 αβ modulated the virus-induced dysregulation of key signaling and inflammatory genes, such as <i>TLR9</i>, <i>TLR3</i>, <i>NOD2</i>, <i>FOS</i>, <i>JUN</i>, <i>IL6</i>, and <i>CXCL8</i>. MD simulation revealed that PLNC8 αβ exhibits higher binding affinity for a flavivirus membrane model compared to a model of the plasma membrane, likely due to stronger electrostatic interactions with anionic phospholipids. This selective interaction possibly accounts for a potent antiviral activity of PLNC8 αβ combined with a minimal cytotoxicity toward human cells. Overall, PLNC8 αβ shows significant promise as an antiviral agent against flavivirus infections and warrants further exploration for peptide-based antiviral therapies.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"16 11","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11599086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142733739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How Do Time Since Diagnosis and Sociodemographic Factors Influence Attitudes Towards HIV Status Disclosure in People Living with HIV in Poland? Data from Go Holistic Go Beyond Project.","authors":"Martyna Lara, Dominik Bursa, Błażej Rozpłochowski, Agata Waszczuk, Monika Bociąga-Jasik, Justyna D Kowalska","doi":"10.3390/v16111771","DOIUrl":"10.3390/v16111771","url":null,"abstract":"<p><p>The aim of this publication is to present the data from Polish respondents of the Go Holistic Go Beyond Project, which investigates social, professional and intimate relations of people living with HIV in Central and Eastern Europe. We analyze how the patients' attitude towards disclosing their HIV status changes over time from diagnosis. A questionnaire was distributed among patients by three HIV out-patient clinics. Respondents were compared in three groups defined by the time from diagnosis: over 10 years ago, 6-10 years ago and within 5 years. In total, 381 persons living with HIV participated in the survey, 354 of respondents were male, 23 were female and 4 of the respondents did not identify with any of the above sexes. A significant decrease in hospital-diagnosed cases (from 53% to 39%) was observed, alongside an increased role of private laboratories and voluntary counseling and testing centers. Eighty-nine percent of participants shared their HIV status with at least one social group. There was no significant change in the patterns of HIV status disclosure, reason and form of HIV testing. Our results emphasize the importance of survey-based studies in identifying the needs of people living with HIV in order to improve their general well-being.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"16 11","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11598971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142733993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Benzocarbazoledinones as SARS-CoV-2 Replication Inhibitors: Synthesis, Cell-Based Studies, Enzyme Inhibition, Molecular Modeling, and Pharmacokinetics Insights.","authors":"Luana G de Souza, Eduarda A Penna, Alice S Rosa, Juliana C da Silva, Edgar Schaeffer, Juliana V Guimarães, Dennis M de Paiva, Vinicius C de Souza, Vivian Neuza S Ferreira, Daniel D C Souza, Sylvia Roxo, Giovanna B Conceição, Larissa E C Constant, Giovanna B Frenzel, Matheus J N Landim, Maria Luiza P Baltazar, Celimar Cinézia Silva, Ana Laura Macedo Brand, Julia Santos Nunes, Tadeu L Montagnoli, Gisele Zapata-Sudo, Marina Amaral Alves, Diego Allonso, Priscila V Z Capriles Goliatt, Milene D Miranda, Alcides J M da Silva","doi":"10.3390/v16111768","DOIUrl":"10.3390/v16111768","url":null,"abstract":"<p><p>Endemic and pandemic viruses represent significant public health challenges, leading to substantial morbidity and mortality over time. The COVID-19 pandemic has underscored the urgent need for the development and discovery of new, potent antiviral agents. In this study, we present the synthesis and anti-SARS-CoV-2 activity of a series of benzocarbazoledinones, assessed using cell-based screening assays. Our results indicate that four compounds (<b>4a</b>, <b>4b</b>, <b>4d</b>, and <b>4i</b>) exhibit EC50 values below 4 μM without cytotoxic effects in Calu-3 cells. Mechanistic investigations focused on the inhibition of the SARS-CoV-2 main protease (Mpro) and papain-like protease (PLpro) have used enzymatic assays. Notably, compounds <b>4a</b> and <b>4b</b> showed Mpro inhibition activity with IC50 values of 0.11 ± 0.05 and 0.37 ± 0.05 µM, respectively. Furthermore, in silico molecular docking, physicochemical, and pharmacokinetic studies were conducted to validate the mechanism and assess bioavailability. Compound <b>4a</b> was selected for preliminary drug-likeness analysis and in vivo pharmacokinetics investigations, which yielded promising results and corroborated the in vitro and in silico findings, reinforcing its potential as an anti-SARS-CoV-2 lead compound.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"16 11","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11598835/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142734004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal ¹H NMR-Based Metabolomics in Saliva Unveils Signatures of Transition from Acute to Post-Acute Phase of SARS-CoV-2 Infection.","authors":"Luiza Tomé Mendes, Marcos C Gama-Almeida, Desirée Lopes Reis, Ana Carolina Pires E Silva, Rômulo Leão Silva Neris, Rafael Mello Galliez, Terezinha Marta Pereira Pinto Castiñeiras, On Behalf Of The Ufrj Covid-Working Group, Christian Ludwig, Ana Paula Valente, Gilson Costa Dos Santos Junior, Tatiana El-Bacha, Iranaia Assunção-Miranda","doi":"10.3390/v16111769","DOIUrl":"10.3390/v16111769","url":null,"abstract":"<p><p>COVID-19 can range from a mild to severe acute respiratory syndrome and also could result in multisystemic damage. Additionally, many people develop post-acute symptoms associated with immune and metabolic disturbances in response to viral infection, requiring longitudinal and multisystem studies to understand the complexity of COVID-19 pathophysiology. Here, we conducted a ¹H Nuclear Magnetic Resonance metabolomics in saliva of symptomatic subjects presenting mild and moderate respiratory symptoms to investigate prospective changes in the metabolism induced after acute-phase SARS-CoV-2 infection. Saliva from 119 donors presenting non-COVID and COVID-19 respiratory symptoms were evaluated in the acute phase (T1) and the post-acute phase (T2). We found two clusters of metabolite fluctuation in the COVID-19 group. Cluster 1, metabolites such as glucose, (CH₃)₃ choline-related metabolites, 2-hydroxybutyrate, BCAA, and taurine increased in T2 relative to T1, and in cluster 2, acetate, creatine/creatinine, phenylalanine, histidine, and lysine decreased in T2 relative to T1. Metabolic fluctuations in the COVID-19 group were associated with overweight/obesity, vaccination status, higher viral load, and viral clearance of the respiratory tract. Our data unveil metabolic signatures associated with the transition to the post-acute phase of SARS-CoV-2 infection that may reflect tissue damage, inflammatory process, and activation of tissue repair cascade. Thus, they contribute to describing alterations in host metabolism that may be associated with prolonged symptoms of COVID-19.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"16 11","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11598993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142734077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Molecular Epidemiology of Echovirus 11 Throughout North and West Africa Resulted in the First Identification of a Recombinant Strain from an Acute Flaccid Paralysis Case in West Africa.","authors":"Ndack Ndiaye, Fatou Diène Thiaw, Adamou Lagare, Thérèse Sinare, Mohamed Lemine Diakité, Serigne Fallou Mbacké Ngom, Ousmane Kébé, Issifi Kollo Abdoulkader, Gassim Cissé, Mohamed Dia, Hermann Nodji Djimadoum, Christelle Ouedraogo Neya, Rakia Boubakar, Issaka Ouedraogo, Landoh Dadja Essoya, Ndongo Dia, Amadou Alpha Sall, Ousmane Faye, Martin Faye","doi":"10.3390/v16111772","DOIUrl":"10.3390/v16111772","url":null,"abstract":"<p><p>Echovirus 11 has emerged as a major public health concern, causing sepsis in neonates in many European countries in recent years. In Africa, especially West Africa, where resources and diagnostic capacities are limited, only sporadic cases have been reported. To better understand the recent molecular epidemiology of E11 in West Africa, we characterized twenty-three echovirus 11 strains isolated through the acute flaccid paralysis and environmental surveillance systems for polio from 2013 to 2023, using high-throughput sequencing. Our data are noteworthy due to identifying for the first time a recombinant strain from an acute flaccid paralysis case and represent the first focus to date on molecular characterization of echovirus 11 in West Africa. Moreover, our data show that echovirus 11 diverged from 1970 (95% HPD range, 1961-1979) and evolved into four distinct clades, with the virus spread from West Africa to Europe, exhibiting two introductions in France around 2017, from Senegal and Guinea. Furthermore, the in silico analysis reveals four non-conservative amino acid substitutions in the VP1 sequences of the European strains associated with neonatal sepsis in newborns and a conserved amino acid motif in the VP1 protein toward enterovirus genotypes. Our data provide new insights into the epidemiology of echovirus 11 and point to the crucial need to implement specific surveillance programs targeting non-polio enteroviruses for the rapid identification of emerging or re-emerging enterovirus species, particularly in Africa.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"16 11","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11599147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142733962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential Replication and Oncolytic Effects of Zika Virus in Aggressive CNS Tumor Cells: Insights from Organoid and Tumoroid Models.","authors":"Rodolfo Sanches Ferreira, Elisa Helena Farias Jandrey, Isabela Granha, Alice Kei Endo, Raiane Oliveira Ferreira, Bruno Henrique Silva Araujo, Mayana Zatz, Oswaldo Keith Okamoto","doi":"10.3390/v16111764","DOIUrl":"10.3390/v16111764","url":null,"abstract":"<p><p>Central nervous system (CNS) cancers are responsible for high rates of morbidity and mortality worldwide. Malignant CNS tumors such as adult Glioblastoma (GBM) and pediatric embryonal CNS tumors such as medulloblastoma (MED) and atypical teratoid rhabdoid tumors (ATRT) present relevant therapeutic challenges due to the lack of response to classic treatment regimens with radio and chemotherapy. Recent findings on the Zika virus' (ZIKV) ability to infect and kill CNS neoplastic cells draw attention to the virus' oncolytic potential. Studies demonstrating the safety of using ZIKV for treating malignant CNS tumors, enabling the translation of this approach to clinical trials, are scarce in the literature. Here we developed a co-culture model of mature human cerebral organoids assembled with GBM, MED or ATRT tumor cells and used these assembloids to test ZIKV oncolytic effect, replication potential and preferential targeting between normal and cancer cells. Our hybrid co-culture models allowed the tracking of tumor cell growth and invasion in cerebral organoids. ZIKV replication and ensuing accumulation in the culture medium was higher in organoids co-cultured with tumor cells than in isolated control organoids without tumor cells. ZIKV infection led to a significant reduction in tumor cell proportion in organoids with GBM and MED cells, but not with ATRT. Tumoroids (3D cultures of tumor cells alone) were efficiently infected by ZIKV. Interestingly, ZIKV rapidly replicated in GBM, MED, and ATRT tumoroids reaching significantly higher viral RNA accumulation levels than co-cultures. Moreover, ZIKV infection reduced viable cells number in MED and ATRT tumoroids but not in GBM tumoroids. Altogether, our findings indicate that ZIKV has greater replication rates in aggressive CNS tumor cells than in normal human cells comprising cerebral organoids. However, such higher ZIKV replication in tumor cells does not necessarily parallels oncolytic effects, suggesting cellular intrinsic and extrinsic factors mediating tumor cell death by ZIKV.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"16 11","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11598871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142734234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Adeno-Associated Virus Replication Protein Rep78 Contains a Strictly C-Terminal Sequence Motif Conserved Across Dependoparvoviruses.","authors":"David G Karlin","doi":"10.3390/v16111760","DOIUrl":"10.3390/v16111760","url":null,"abstract":"<p><p>Adeno-Associated Viruses (AAVs, genus <i>Dependoparvovirus</i>) are the leading gene therapy vector. Until recently, efforts to enhance their capacity for gene delivery had focused on their capsids. However, efforts are increasingly shifting towards improving the viral replication protein, Rep78. We discovered that Rep78 and its shorter isoform Rep52 contain a strictly C-terminal sequence motif, DDx3EQ, conserved in most dependoparvoviruses. The motif is highly negatively charged and devoid of prolines. Its wide conservation suggests that it is required for the life cycle of dependoparvoviruses. Despite its short length, the motif's strictly C-terminal position has the potential to endow it with a high recognition specificity. A candidate target of the DDx3EQ motif might be the DNA-binding interface of the origin-binding domain of Rep78, which is highly positively charged. Published studies suggest that this motif is not required for recombinant AAV production, but that substitutions within it might improve production.</p>","PeriodicalId":49328,"journal":{"name":"Viruses-Basel","volume":"16 11","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11598897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142734142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}