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Deimmunization of flagellin adjuvant for clinical application 鞭毛蛋白佐剂的临床脱免疫研究
IF 5.9 2区 医学
Current opinion in virology Pub Date : 2023-06-01 DOI: 10.1016/j.coviro.2023.101330
Joon Haeng Rhee , Koemchhoy Khim , Sao Puth , Yoonjoo Choi , Shee Eun Lee
{"title":"Deimmunization of flagellin adjuvant for clinical application","authors":"Joon Haeng Rhee ,&nbsp;Koemchhoy Khim ,&nbsp;Sao Puth ,&nbsp;Yoonjoo Choi ,&nbsp;Shee Eun Lee","doi":"10.1016/j.coviro.2023.101330","DOIUrl":"10.1016/j.coviro.2023.101330","url":null,"abstract":"<div><p>Flagellin is the cognate ligand for host pattern recognition receptors, toll-like receptor 5 (TLR5) in the cell surface, and NAIP5/NLRC4 inflammasome in the cytosol. TLR5-binding domain is located in D1 domain, where crucial amino acid sequences are conserved among diverse bacteria. The highly conserved C-terminal 35 amino acids of flagellin were proved to be responsible for the inflammasome activation by binding to NAIP5. D2/D3 domains, located in the central region and exposed to the outside surface of flagellar filament, are heterogeneous across bacterial species and highly immunogenic. Taking advantage of TLR5- and NLRC4-stimulating activities, flagellin has been actively developed as a vaccine adjuvant and immunotherapeutic. Because of its immunogenicity, there exist worries concerning diminished efficacy and possible reactogenicity after repeated administration. Deimmunization of flagellin derivatives while preserving the TLR5/NLRC4-mediated immunomodulatory activity should be the most reasonable option for clinical application. This review describes strategies and current achievements in flagellin deimmunization.</p></div>","PeriodicalId":11082,"journal":{"name":"Current opinion in virology","volume":"60 ","pages":"Article 101330"},"PeriodicalIF":5.9,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9660573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The two faces of oligoadenylate synthetase-like: effective antiviral protein and negative regulator of innate immunity 寡腺苷酸合成酶样的两面性：有效的抗病毒蛋白和先天免疫的负调节因子
IF 5.9 2区 医学
Current opinion in virology Pub Date : 2023-06-01 DOI: 10.1016/j.coviro.2023.101329
Viktoria Rex , Markus Stempel , Stephan Halle , Melanie M Brinkmann
{"title":"The two faces of oligoadenylate synthetase-like: effective antiviral protein and negative regulator of innate immunity","authors":"Viktoria Rex ,&nbsp;Markus Stempel ,&nbsp;Stephan Halle ,&nbsp;Melanie M Brinkmann","doi":"10.1016/j.coviro.2023.101329","DOIUrl":"10.1016/j.coviro.2023.101329","url":null,"abstract":"<div><p>The type I interferon response is critical for controlling viral infection and triggers the production of downstream-target genes, termed interferon-stimulated genes (ISGs). While ISGs have a plethora of ways to restrict viruses at different stages of their replication cycle, they are also important to dampen immune responses to avoid tissue damage in the case of exuberant effects. However, this counter regulation of the immune response comes with the downside that it can open a door for viruses to get a foothold in their host. One key family of ISGs is the oligoadenylate synthetase (OAS) family, consisting of the DNA sensor cGAS and the RNA-sensing OAS and oligoadenylate synthetase-like (OASL) proteins. OASL proteins are of particular interest since they are structurally unique and act like a double-edged sword during immune responses to viral infection: they act antiviral, primarily against RNA viruses, whereas most DNA viruses benefit from OASL expression. Here, we put this balancing act of OASL proteins from different species into the spotlight and portray their different faces to viral infections.</p></div>","PeriodicalId":11082,"journal":{"name":"Current opinion in virology","volume":"60 ","pages":"Article 101329"},"PeriodicalIF":5.9,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10015781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Does arbovirus emergence in humans require adaptation to domestic mosquitoes? 虫媒病毒在人类中的出现是否需要适应家养蚊子?
IF 5.9 2区 医学
Current opinion in virology Pub Date : 2023-06-01 DOI: 10.1016/j.coviro.2023.101315
Louis Lambrechts
{"title":"Does arbovirus emergence in humans require adaptation to domestic mosquitoes?","authors":"Louis Lambrechts","doi":"10.1016/j.coviro.2023.101315","DOIUrl":"10.1016/j.coviro.2023.101315","url":null,"abstract":"<div><p>In the last few decades, several mosquito-borne arboviruses of zoonotic origin have established large-scale epidemic transmission cycles in the human population. It is often considered that arbovirus emergence is driven by adaptive evolution, such as virus adaptation for transmission by ‘domestic’ mosquito vector species that live in close association with humans. Here, I argue that although arbovirus adaptation to domestic mosquito vectors has been observed for several emerging arboviruses, it was generally not directly responsible for their initial emergence. Secondary adaptation to domestic mosquitoes often amplified epidemic transmission, however, this was more likely a consequence than a cause of arbovirus emergence. Considering that emerging arboviruses are generally ‘preadapted’ for transmission by domestic mosquito vectors may help to enhance preparedness toward future arbovirus emergence events.</p></div>","PeriodicalId":11082,"journal":{"name":"Current opinion in virology","volume":"60 ","pages":"Article 101315"},"PeriodicalIF":5.9,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9663178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Viral determinants influencing intra- and intercellular communication in cytomegalovirus infection 巨细胞病毒感染中影响细胞内和细胞间通讯的病毒决定因素
IF 5.9 2区 医学
Current opinion in virology Pub Date : 2023-06-01 DOI: 10.1016/j.coviro.2023.101328
Katarzyna Szymanska-de Wijs , Martina Dezeljin , Boris Bogdanow , Martin Messerle
{"title":"Viral determinants influencing intra- and intercellular communication in cytomegalovirus infection","authors":"Katarzyna Szymanska-de Wijs ,&nbsp;Martina Dezeljin ,&nbsp;Boris Bogdanow ,&nbsp;Martin Messerle","doi":"10.1016/j.coviro.2023.101328","DOIUrl":"10.1016/j.coviro.2023.101328","url":null,"abstract":"<div><p>Cytomegaloviruses (CMVs) are typically disseminated by cell-to-cell transfer, which requires reprogramming of cellular signaling pathways and restructuring of the cell architecture. Viral particles not only transfer genetic information between cells, but also tegument proteins that enable the virus to counteract cellular defense mechanisms immediately upon entering cells. The UL25 gene family of CMVs encodes such tegument proteins and also gives rise to related nonstructural proteins expressed early in infection. Herein, we report on the functions attributed to UL25 family members of several β-herpesviruses, particularly to the M25 proteins of mouse CMV that were found to interfere with the antiviral role of the p53 tumor suppressor protein and to mediate cytoskeleton rearrangement of infected cells.</p></div>","PeriodicalId":11082,"journal":{"name":"Current opinion in virology","volume":"60 ","pages":"Article 101328"},"PeriodicalIF":5.9,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10015296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Diagnosis and monitoring of virus-associated cancer using cell-free DNA 利用无细胞DNA诊断和监测病毒相关癌症
IF 5.9 2区 医学
Current opinion in virology Pub Date : 2023-06-01 DOI: 10.1016/j.coviro.2023.101331
Larissa LS Scholte , Jeffrey M Bethony , Rena R Xian
{"title":"Diagnosis and monitoring of virus-associated cancer using cell-free DNA","authors":"Larissa LS Scholte ,&nbsp;Jeffrey M Bethony ,&nbsp;Rena R Xian","doi":"10.1016/j.coviro.2023.101331","DOIUrl":"10.1016/j.coviro.2023.101331","url":null,"abstract":"<div><p>Viral-associated cancers are a distinct group of malignancies with a unique pathogenesis and epidemiology. Liquid biopsy is a minimally invasive way to identify tumor-associated abnormalities in blood derivatives, such as plasma, to guide the diagnosis, prognosis, and treatment of patients with cancer. Liquid biopsy encompasses a multitude of circulating analytes with the most extensively studied being cell-free DNA (cfDNA). In recent decades, substantial advances have been made toward the study of circulating tumor DNA in nonviral-associated cancers. Many of these observations have been translated to the clinic to improve the outcomes of patients with cancer. The study of cfDNA in viral-associated cancers is rapidly evolving and reveals tremendous potential for clinical applications. This review provides an overview of the pathogenesis of viral-associated malignancies, the current state of cfDNA analysis in oncology, the current state of cfDNA analysis in viral-associated cancers, and perspectives for the future of liquid biopsies in viral-associated cancers.</p></div>","PeriodicalId":11082,"journal":{"name":"Current opinion in virology","volume":"60 ","pages":"Article 101331"},"PeriodicalIF":5.9,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9714213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
The role of human lipoproteins for hepatitis C virus persistence 人脂蛋白对丙型肝炎病毒持久性的作用
IF 5.9 2区 医学
Current opinion in virology Pub Date : 2023-06-01 DOI: 10.1016/j.coviro.2023.101327
Gabrielle Vieyres , Thomas Pietschmann
{"title":"The role of human lipoproteins for hepatitis C virus persistence","authors":"Gabrielle Vieyres ,&nbsp;Thomas Pietschmann","doi":"10.1016/j.coviro.2023.101327","DOIUrl":"10.1016/j.coviro.2023.101327","url":null,"abstract":"<div><p>Hepatitis C virus (HCV) is a hepatotropic virus that establishes a chronic infection in most individuals. Effective treatments are available; however, many patients are not aware of their infection. Consequently, they do not receive treatment and HCV transmission remains high, particularly among groups at high risk of exposure such as people who inject intravenous drugs. A prophylactic vaccine may reduce HCV transmission, but is currently not available. HCV has evolved immune evasion strategies, which facilitate persistence and complicate development of a protective vaccine. The peculiar association of HCV particles with human lipoproteins is thought to facilitate evasion from humoral immune response and viral homing to liver cells. A better understanding of these aspects provides the basis for development of protective vaccination strategies. Here, we review key information about the composition of HCV particles, the mechanisms mediating lipoprotein incorporation, and the functional consequences of this interaction.</p></div>","PeriodicalId":11082,"journal":{"name":"Current opinion in virology","volume":"60 ","pages":"Article 101327"},"PeriodicalIF":5.9,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10015295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Flavivirus nonstructural proteins and replication complexes as antiviral drug targets 黄病毒非结构蛋白和复制复合体作为抗病毒药物靶点
IF 5.9 2区 医学
Current opinion in virology Pub Date : 2023-04-01 DOI: 10.1016/j.coviro.2023.101305
Kaïn van den Elsen , Bing Liang Alvin Chew , Jun Sheng Ho , Dahai Luo
{"title":"Flavivirus nonstructural proteins and replication complexes as antiviral drug targets","authors":"Kaïn van den Elsen ,&nbsp;Bing Liang Alvin Chew ,&nbsp;Jun Sheng Ho ,&nbsp;Dahai Luo","doi":"10.1016/j.coviro.2023.101305","DOIUrl":"10.1016/j.coviro.2023.101305","url":null,"abstract":"<div><p>Many flaviviruses are well-known pathogens, such as dengue, Zika, Japanese encephalitis, and yellow fever viruses. Among them, dengue viruses cause global epidemics and threaten billions of people. Effective vaccines and antivirals are in desperate need. In this review, we focus on the recent advances in understanding viral nonstructural (NS) proteins as antiviral drug targets. We briefly summarize the experimental structures and predicted models of flaviviral NS proteins and their functions. We highlight a few well-characterized inhibitors targeting these NS proteins and provide an update about the latest development. NS4B emerges as one of the most promising drug targets as novel inhibitors targeting NS4B and its interaction network are entering clinical studies. Studies aiming to elucidate the architecture and molecular basis of viral replication will offer new opportunities for novel antiviral discovery. Direct-acting agents against dengue and other pathogenic flaviviruses may be available very soon.</p></div>","PeriodicalId":11082,"journal":{"name":"Current opinion in virology","volume":"59 ","pages":"Article 101305"},"PeriodicalIF":5.9,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10023477/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9624964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
HIV persistence: silence or resistance? 艾滋病毒的持久性：沉默还是抵抗？
IF 5.9 2区 医学
Current opinion in virology Pub Date : 2023-04-01 DOI: 10.1016/j.coviro.2023.101301
Alexander O Pasternak, Ben Berkhout
{"title":"HIV persistence: silence or resistance?","authors":"Alexander O Pasternak,&nbsp;Ben Berkhout","doi":"10.1016/j.coviro.2023.101301","DOIUrl":"10.1016/j.coviro.2023.101301","url":null,"abstract":"<div><p>Despite decades of suppressive antiretroviral therapy, human immunodeficiency virus (HIV) reservoirs in infected individuals persist and fuel viral rebound once therapy is interrupted. The persistence of viral reservoirs is the main obstacle to achieving HIV eradication or a long-term remission. The last decade has seen a profound change in our understanding of the mechanisms behind HIV persistence, which appears to be much more complex than originally assumed. In addition to the persistence of transcriptionally silent proviruses in a stable latent reservoir that is invisible to the immune system, HIV is increasingly recognized to persist by resistance to the immune clearance, which appears to play a surprisingly prominent role in shaping the reservoir. In this review, we discuss some emerging insights into the mechanisms of HIV persistence, as well as their implications for the development of strategies towards an HIV cure.</p></div>","PeriodicalId":11082,"journal":{"name":"Current opinion in virology","volume":"59 ","pages":"Article 101301"},"PeriodicalIF":5.9,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9248884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 8
Interplay of RNA 2′-O-methylations with viral replication RNA 2′-O-甲基化与病毒复制的相互作用
IF 5.9 2区 医学
Current opinion in virology Pub Date : 2023-04-01 DOI: 10.1016/j.coviro.2023.101302
Alice Decombe, Priscila El Kazzi, Etienne Decroly
{"title":"Interplay of RNA 2′-O-methylations with viral replication","authors":"Alice Decombe,&nbsp;Priscila El Kazzi,&nbsp;Etienne Decroly","doi":"10.1016/j.coviro.2023.101302","DOIUrl":"10.1016/j.coviro.2023.101302","url":null,"abstract":"<div><p>Viral RNAs (vRNAs) are decorated by post-transcriptional modifications, including methylation of nucleotides. Methylations regulate biological functions linked to the sequence, structure, and protein interactome of RNA. Several RNA viruses were found to harbor 2′-O-methylations, affecting the ribose moiety of RNA. This mark was initially shown to target the first and second nucleotides of the 5′-end cap structure of mRNA. More recently, nucleotides within vRNA were also reported to carry 2′-O-methylations. The consequences of such methylations are still puzzling since they were associated with both proviral and antiviral effects. Here, we focus on the mechanisms governing vRNA 2′-O-methylation and we explore the possible roles of this epitranscriptomic modification for viral replication.</p></div>","PeriodicalId":11082,"journal":{"name":"Current opinion in virology","volume":"59 ","pages":"Article 101302"},"PeriodicalIF":5.9,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9261650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
MEK inhibitors as novel host-targeted antivirals with a dual-benefit mode of action against hyperinflammatory respiratory viral diseases MEK抑制剂作为一种新的宿主靶向抗病毒药物，对高炎症性呼吸道病毒性疾病具有双重益处
IF 5.9 2区 医学
Current opinion in virology Pub Date : 2023-04-01 DOI: 10.1016/j.coviro.2023.101304
Stephan Ludwig , Stephan Pleschka , Oliver Planz
{"title":"MEK inhibitors as novel host-targeted antivirals with a dual-benefit mode of action against hyperinflammatory respiratory viral diseases","authors":"Stephan Ludwig ,&nbsp;Stephan Pleschka ,&nbsp;Oliver Planz","doi":"10.1016/j.coviro.2023.101304","DOIUrl":"10.1016/j.coviro.2023.101304","url":null,"abstract":"<div><p>Acute hyperinflammatory virus infections, such as influenza or coronavirus disease-19, are still a major health burden worldwide. In these diseases, a massive overproduction of pro-inflammatory cytokines and chemokines (cytokine storm syndrome) determine the severity of the disease, especially in late stages. Direct-acting antivirals against these pathogens have to be administered very early after infection to be effective and may induce viral resistance. Here, we summarize data on a host-targeted strategy using inhibitors of the cellular Raf/MEK/ERK kinase cascade that not only block replication of different RNA viruses but also suppress the hyperinflammatory cytokine response upon infection. In the first phase-II clinical trial of that approach, the MEK inhibitor Zapnometinib shows evidence of clinical benefit.</p></div>","PeriodicalId":11082,"journal":{"name":"Current opinion in virology","volume":"59 ","pages":"Article 101304"},"PeriodicalIF":5.9,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10091867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9298283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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