Daming Zhou , Jingshan Ren , Elizabeth E Fry , David I Stuart
{"title":"Broadly neutralizing antibodies against COVID-19","authors":"Daming Zhou , Jingshan Ren , Elizabeth E Fry , David I Stuart","doi":"10.1016/j.coviro.2023.101332","DOIUrl":"10.1016/j.coviro.2023.101332","url":null,"abstract":"<div><p>The COVID-19 pandemic caused by SARS-CoV-2 has led to hundreds of millions of infections and millions of deaths, however, human monoclonal antibodies (mAbs) can be an effective treatment. Since SARS-CoV-2 emerged, a variety of strains have acquired increasing numbers of mutations to gain increased transmissibility and escape from the immune response. Most reported neutralizing human mAbs, including all approved therapeutic ones, have been knocked down or out by these mutations. Broadly neutralizing mAbs are therefore of great value, to treat current and possible future variants. Here, we review four types of neutralizing mAbs against the spike protein with broad potency against previously and currently circulating variants. These mAbs target the receptor-binding domain, the subdomain 1, the stem helix, or the fusion peptide. Understanding how these mAbs retain potency in the face of mutational change could guide future development of therapeutic antibodies and vaccines.</p></div>","PeriodicalId":11082,"journal":{"name":"Current opinion in virology","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10301462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9940702","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}
Ilona I Tosheva , Kain S Saygan , Suzanne MA Mijnhardt , Charles J Russell , Pieter LA Fraaij , Sander Herfst
{"title":"Hemagglutinin stability as a key determinant of influenza A virus transmission via air","authors":"Ilona I Tosheva , Kain S Saygan , Suzanne MA Mijnhardt , Charles J Russell , Pieter LA Fraaij , Sander Herfst","doi":"10.1016/j.coviro.2023.101335","DOIUrl":"10.1016/j.coviro.2023.101335","url":null,"abstract":"<div><p>To cause pandemics, zoonotic respiratory viruses need to adapt to replication in and spread between humans, either via (indirect or direct) contact or through the air via droplets and aerosols. To render influenza A viruses transmissible via air, three phenotypic viral properties must change, of which receptor-binding specificity and polymerase activity have been well studied. However, the third adaptive property, hemagglutinin (HA) acid stability, is less understood. Recent studies show that there may be a correlation between HA acid stability and virus survival in the air, suggesting that a premature conformational change of HA, triggered by low pH in the airways or droplets, may render viruses noninfectious before they can reach a new host. We here summarize available data from (animal) studies on the impact of HA acid stability on airborne transmission and hypothesize that the transmissibility of other respiratory viruses may also be impacted by an acidic environment in the airways.</p></div>","PeriodicalId":11082,"journal":{"name":"Current opinion in virology","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9941242","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}
{"title":"Predicting zoonotic potential of viruses: where are we?","authors":"Nardus Mollentze , Daniel G Streicker","doi":"10.1016/j.coviro.2023.101346","DOIUrl":"10.1016/j.coviro.2023.101346","url":null,"abstract":"<div><p>The prospect of identifying high-risk viruses and designing interventions to pre-empt their emergence into human populations is enticing, but controversial, particularly when used to justify large-scale virus discovery initiatives. We review the current state of these efforts, identifying three broad classes of predictive models that have differences in data inputs that define their potential utility for triaging newly discovered viruses for further investigation. Prospects for model predictions of public health risk to guide preparedness depend not only on computational improvements to algorithms, but also on more efficient data generation in laboratory, field and clinical settings. Beyond public health applications, efforts to predict zoonoses provide unique research value by creating generalisable understanding of the ecological and evolutionary factors that promote viral emergence.</p></div>","PeriodicalId":11082,"journal":{"name":"Current opinion in virology","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9953771","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}
{"title":"Structural basis for respiratory syncytial virus and human metapneumovirus neutralization","authors":"Rose J Miller , Jarrod J Mousa","doi":"10.1016/j.coviro.2023.101337","DOIUrl":"10.1016/j.coviro.2023.101337","url":null,"abstract":"<div><p>Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) continue to be a global burden to infants, the elderly, and immunocompromised individuals. In the past ten years, there has been substantial progress in the development of new vaccine candidates and therapies against these viruses. These advancements were guided by the structural elucidation of the major surface glycoproteins for these viruses, the fusion (F) protein and attachment (G) protein. The identification of immunodominant epitopes on the RSV F and hMPV F proteins has expanded current knowledge on antibody-mediated immune responses, which has led to new approaches for vaccine and therapeutic development through the stabilization of pre-fusion constructs of the F protein and pre-fusion-specific monoclonal antibodies with high potency and efficacy. In this review, we describe structural characteristics of known antigenic sites on the RSV and hMPV proteins, their influence on the immune response, and current progress in vaccine and therapeutic development.</p></div>","PeriodicalId":11082,"journal":{"name":"Current opinion in virology","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10421620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10050641","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}
{"title":"Kaposi sarcoma-associated herpesvirus latency-associated nuclear antigen: more than a key mediator of viral persistence","authors":"Thomas F Schulz , Anika Freise , Saskia C Stein","doi":"10.1016/j.coviro.2023.101336","DOIUrl":"10.1016/j.coviro.2023.101336","url":null,"abstract":"<div><p>Kaposi sarcoma-associated herpesvirus (KSHV), or human herpesvirus-8, is an oncogenic herpesvirus. Its latency-associated nuclear antigen (LANA) is essential for the persistence of KSHV in latently infected cells. LANA mediates replication of the latent viral genome during the S phase of a dividing cell and partitions episomes to daughter cells by attaching them to mitotic chromosomes. It also mediates the establishment of latency in newly infected cells through epigenetic mechanisms and suppresses the activation of the productive replication cycle. Furthermore, LANA promotes the proliferation of infected cell by acting as a transcriptional regulator and by modulating the cellular proteome through the recruitment of several cellular ubiquitin ligases. Finally, LANA interferes with the innate and adaptive immune system to facilitate the immune escape of infected cells.</p></div>","PeriodicalId":11082,"journal":{"name":"Current opinion in virology","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9941254","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}
{"title":"Cryo-electron tomography of viral infection — from applications to biosafety","authors":"Liv Zimmermann, Petr Chlanda","doi":"10.1016/j.coviro.2023.101338","DOIUrl":"10.1016/j.coviro.2023.101338","url":null,"abstract":"<div><p>Cellular cryo-electron tomography (cryo-ET) offers 3D snapshots at molecular resolution capturing pivotal steps during viral infection. However, tomogram quality depends on the vitrification level of the sample and its thickness. In addition, mandatory inactivation protocols to assure biosafety when handling highly pathogenic viruses during cryo-ET can compromise sample preservation. Here, we focus on different strategies applied in cryo-ET and discuss their advantages and limitations with reference to severe acute respiratory syndrome coronavirus 2 studies. We highlight the importance of virus-like particle (VLP) and replicon systems to study virus assembly and replication in a cellular context without inactivation protocols. We discuss the application of chemical fixation and different irradiation methods in cryo-ET sample preparation and acquisition workflows.</p></div>","PeriodicalId":11082,"journal":{"name":"Current opinion in virology","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10003745","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}
Sam Afkhami, Alisha Kang, Vidthiya Jeyanathan, Zhou Xing, Mangalakumari Jeyanathan
{"title":"Adenoviral-vectored next-generation respiratory mucosal vaccines against COVID-19","authors":"Sam Afkhami, Alisha Kang, Vidthiya Jeyanathan, Zhou Xing, Mangalakumari Jeyanathan","doi":"10.1016/j.coviro.2023.101334","DOIUrl":"10.1016/j.coviro.2023.101334","url":null,"abstract":"<div><p>The world is in need of next-generation COVID-19 vaccines. Although first-generation injectable COVID-19 vaccines continue to be critical tools in controlling the current global health crisis, continuous emergence of SARS-CoV-2 variants of concern has eroded the efficacy of these vaccines, leading to staggering breakthrough infections and posing threats to poor vaccine responders. This is partly because the humoral and T-cell responses generated following intramuscular injection of spike-centric monovalent vaccines are mostly confined to the periphery, failing to either access or be maintained at the portal of infection, the respiratory mucosa (RM). In contrast, respiratory mucosal-delivered vaccine can induce immunity encompassing humoral, cellular, and trained innate immunity positioned at the respiratory mucosa that may act quickly to prevent the establishment of an infection. Viral vectors, especially adenoviruses, represent the most promising platform for RM delivery that can be designed to express both structural and nonstructural antigens of SARS-CoV-2. Boosting RM immunity via the respiratory route using multivalent adenoviral-vectored vaccines would be a viable next-generation vaccine strategy.</p></div>","PeriodicalId":11082,"journal":{"name":"Current opinion in virology","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10172971/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10306080","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}
Mengying Liu, Frank JM van Kuppeveld, Cornelis AM de Haan, Erik de Vries
{"title":"Gradual adaptation of animal influenza A viruses to human-type sialic acid receptors","authors":"Mengying Liu, Frank JM van Kuppeveld, Cornelis AM de Haan, Erik de Vries","doi":"10.1016/j.coviro.2023.101314","DOIUrl":"10.1016/j.coviro.2023.101314","url":null,"abstract":"<div><p>Influenza A viruses (IAVs) originating from animal reservoirs pose continuous threats to human health as demonstrated by the Spanish flu pandemic. Infection starts by attachment to host receptors, a crucial step that is targeted by immunological, prophylactic, and therapeutic intervention. Fine-tuning of virus hemagglutinin binding to host-specific receptor repertoires needs to remain balanced to receptor-destroying neuraminidase (NA) activity and is a key step in host adaptation. It determines NA-dependent virus motility, enabling IAVs to traverse the mucus layer and to bind to, and migrate over, the epithelial cell surface for reaching a location supporting endocytic uptake. Canonical adaptations in enzootic/zoonotic IAVs enhancing human-type receptor binding are well-known, but the context and timespan required for their selection pose many questions. We discuss recent developments, focusing on the dynamic nature of interactions of IAV with the heterogeneous receptor repertoires present in humans and potential intermediate hosts. Potential pre-adaption toward human-type receptor binding in intermediate hosts will be discussed.</p></div>","PeriodicalId":11082,"journal":{"name":"Current opinion in virology","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9650688","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}
{"title":"Structural insights into hepatitis C virus neutralization","authors":"Luisa J. Ströh , Thomas Krey","doi":"10.1016/j.coviro.2023.101316","DOIUrl":"10.1016/j.coviro.2023.101316","url":null,"abstract":"<div><p>Inspite of the available antiviral therapy, hepatitis C virus (HCV) remains a global health burden and a prophylactic vaccine would help to eliminate the risk to develop chronic liver diseases. Structural insights into the function of the glycoproteins E1 and E2 in virus entry and the interplay with the host’s humoral immune response are key for informed vaccine development. We review recently reported structural insights into receptor binding of HCV glycoproteins and the assembly of an intact membrane-bound E1–E2 heterodimer. These data are used together with available functional data to draw a simplified model of virus entry, which highlights gaps in our current knowledge that warrant further research to fully understand this process at the atomic level.</p></div>","PeriodicalId":11082,"journal":{"name":"Current opinion in virology","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9650689","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}
Rajbir K Toor , Eleanor C Semmes , Kyle M Walsh , Sallie R Permar , Lisa Giulino-Roth
{"title":"Does congenital cytomegalovirus infection contribute to the development of acute lymphoblastic leukemia in children?","authors":"Rajbir K Toor , Eleanor C Semmes , Kyle M Walsh , Sallie R Permar , Lisa Giulino-Roth","doi":"10.1016/j.coviro.2023.101325","DOIUrl":"10.1016/j.coviro.2023.101325","url":null,"abstract":"<div><p>Cytomegalovirus (CMV) is a ubiquitous herpesvirus that has a profound impact on the host immune system. Congenital cytomegalovirus (cCMV) infection modulates neonatal immune cell compartments, yet the full impact of <em>in utero</em> exposure on developing fetal immune cells remains poorly characterized. A series of recent studies have identified a potential link between cCMV infection and the development of acute lymphoblastic leukemia (ALL) in childhood. Here, we review the emerging evidence linking CMV and ALL risk, discuss what is known about the causes of childhood ALL, and propose how CMV infection in early life may confer increased ALL risk.</p></div>","PeriodicalId":11082,"journal":{"name":"Current opinion in virology","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9704215","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}