scholarly journals The Antiviral Mechanism of an Influenza A Virus Nucleoprotein-Specific Single-Domain Antibody Fragment

mBio ◽  
2016 ◽  
Vol 7 (6) ◽  
Author(s):  
Leo Hanke ◽  
Kevin E. Knockenhauer ◽  
R. Camille Brewer ◽  
Eline van Diest ◽  
Florian I. Schmidt ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A Virus ◽  
Influenza A ◽  
Influenza Virus Infection ◽  
Antibody Fragment ◽  
Antibody Fragments ◽  
The Body ◽  
Single Domain ◽  
Single Domain Antibody ◽  
Domain Antibody

ABSTRACTAlpaca-derived single-domain antibody fragments (VHHs) that target the influenza A virus nucleoprotein (NP) can protect cells from infection when expressed in the cytosol. We found that one such VHH, αNP-VHH1, exhibits antiviral activity similar to that of Mx proteins by blocking nuclear import of incoming viral ribonucleoproteins (vRNPs) and viral transcription and replication in the nucleus. We determined a 3.2-Å crystal structure of αNP-VHH1 in complex with influenza A virus NP. The VHH binds to a nonconserved region on the body domain of NP, which has been associated with binding to host factors and serves as a determinant of host range. Several of the NP/VHH interface residues determine sensitivity of NP to antiviral Mx GTPases. The structure of the NP/αNP-VHH1 complex affords a plausible explanation for the inhibitory properties of the VHH and suggests a rationale for the antiviral properties of Mx proteins. Such knowledge can be leveraged for much-needed novel antiviral strategies.IMPORTANCEInfluenza virus strains can rapidly escape from protection afforded by seasonal vaccines or acquire resistance to available drugs. Additional ways to interfere with the virus life cycle are therefore urgently needed. The influenza virus nucleoprotein is one promising target for antiviral interventions. We have previously isolated alpaca-derived single-domain antibody fragments (VHHs) that protect cells from influenza virus infection if expressed intracellularly. We show here that one such VHH exhibits antiviral activities similar to those of proteins of the cellular antiviral defense (Mx proteins). We determined the three-dimensional structure of this VHH in complex with the influenza virus nucleoprotein and identified the interaction site, which overlaps regions that determine sensitivity of the virus to Mx proteins. Our data define a new vulnerability of influenza virus, help us to better understand the cellular antiviral mechanisms, and provide a well-characterized tool to further study them.

scholarly journals Isolation of Panels of Llama Single-Domain Antibody Fragments Binding All Nine Neuraminidase Subtypes of Influenza A Virus

Antibodies ◽  
2013 ◽  
Vol 2 (4) ◽  
pp. 168-192 ◽  
Author(s):  
Michiel Harmsen ◽  
Juliette Blokker ◽  
Sylvia Pritz-Verschuren ◽  
Willem Bartelink ◽  
Herman van der Burg ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Antibody Fragments ◽  
Single Domain ◽  
Single Domain Antibody ◽  
Domain Antibody

scholarly journals mRNA Encoding a Bispecific Single Domain Antibody Construct Protects against Influenza A Virus Infection in Mice

2020 ◽  
Vol 20 ◽  
pp. 777-787
Author(s):  
Lien Van Hoecke ◽  
Rein Verbeke ◽  
Dorien De Vlieger ◽  
Heleen Dewitte ◽  
Kenny Roose ◽  
...  
Keyword(s):  
Virus Infection ◽  
Influenza A Virus ◽  
Influenza A ◽  
Single Domain ◽  
Single Domain Antibody ◽  
Domain Antibody ◽  
Influenza A Virus Infection

scholarly journals Potent Neutralization of Influenza A Virus by a Single-Domain Antibody Blocking M2 Ion Channel Protein

PLoS ONE ◽  
2011 ◽  
Vol 6 (12) ◽  
pp. e28309 ◽  
Author(s):  
Guowei Wei ◽  
Weixu Meng ◽  
Haijiang Guo ◽  
Weiqi Pan ◽  
Jinsong Liu ◽  
...  
Keyword(s):  
Ion Channel ◽  
Influenza A Virus ◽  
Influenza A ◽  
Single Domain ◽  
Single Domain Antibody ◽  
Channel Protein ◽  
Domain Antibody ◽  
Potent Neutralization

scholarly journals Influenza A Virus Hemagglutinin and Other Pathogen Glycoprotein Interactions with NK Cell Natural Cytotoxicity Receptors NKp46, NKp44, and NKp30

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 156
Author(s):  
Jasmina M. Luczo ◽  
Sydney L. Ronzulli ◽  
Stephen M. Tompkins
Keyword(s):  
Influenza Virus ◽  
Nk Cells ◽  
Influenza A Virus ◽  
Influenza A ◽  
Nk Cell ◽  
Influenza Virus Infection ◽  
Target Cells ◽  
Natural Cytotoxicity ◽  
Activating Receptors ◽  
Natural Cytotoxicity Receptors

Natural killer (NK) cells are part of the innate immunity repertoire, and function in the recognition and destruction of tumorigenic and pathogen-infected cells. Engagement of NK cell activating receptors can lead to functional activation of NK cells, resulting in lysis of target cells. NK cell activating receptors specific for non-major histocompatibility complex ligands are NKp46, NKp44, NKp30, NKG2D, and CD16 (also known as FcγRIII). The natural cytotoxicity receptors (NCRs), NKp46, NKp44, and NKp30, have been implicated in functional activation of NK cells following influenza virus infection via binding with influenza virus hemagglutinin (HA). In this review we describe NK cell and influenza A virus biology, and the interactions of influenza A virus HA and other pathogen lectins with NK cell natural cytotoxicity receptors (NCRs). We review concepts which intersect viral immunology, traditional virology and glycobiology to provide insights into the interactions between influenza virus HA and the NCRs. Furthermore, we provide expert opinion on future directions that would provide insights into currently unanswered questions.

Over expression of anti-MUC1 single-domain antibody fragments in the yeast Pichia pastoris

2006 ◽  
Vol 43 (5) ◽  
pp. 426-435 ◽  
Author(s):  
Fatemeh Rahbarizadeh ◽  
Mohammad J. Rasaee ◽  
Mehdi Forouzandeh ◽  
Abdol-Amir Allameh
Keyword(s):  
Pichia Pastoris ◽  
Antibody Fragments ◽  
Single Domain ◽  
Single Domain Antibody ◽  
Yeast Pichia Pastoris ◽  
Over Expression ◽  
Domain Antibody

scholarly journals Routine blood parameters are helpful for early identification of influenza infection in children

2020 ◽  
Author(s):  
Ronghe Zhu ◽  
Cuie Chen ◽  
Qiu Wang ◽  
Xixi Zhang ◽  
Chaosheng Lu ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Influenza A Virus ◽  
Early Identification ◽  
Influenza A ◽  
Influenza Infection ◽  
Influenza Virus Infection ◽  
Cutoff Value ◽  
Routine Blood ◽  
Influenza A Virus Infection

Abstract Purpose Routine blood parameters, such as the lymphocyte (LYM) count, platelet (PLT) count, lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), LYM*PLT and mean platelet volume-to-platelet ratio (MPV/PLT), are widely used to predict the prognosis of infectious diseases. We aimed to explore the value of these parameters in the early identification of influenza virus infection in children.Methods We conducted a single-center, retrospective, observational study of fever with influenza-like symptoms in pediatric outpatients from different age groups and evaluated the predictive value of various routine blood parameters measured within 48 hours of the onset of fever for influenza virus infection.Results The LYM count, PLT count, LMR and LYM*PLT were lower, and the NLR and MPV/PLT were higher in children with an influenza infection (PCR-confirmed and symptomatic). The LYM count, LMR and LYM*PLT in the influenza infection group were lower in the 1- to 6-year-old subgroup, and the LMR and LYM*PLT in the influenza infection group were lower in the >6-year-old subgroup. In the 1- to 6-year-old subgroup, the cutoff value of the LMR for predicting influenza A virus infection was 3.75, the sensitivity was 81.87%, the specificity was 84.31%, and the area under the curve (AUC) was 0.886; the cutoff value of the LMR for predicting influenza B virus infection was 3.71, the sensitivity was 73.58%, the specificity was 84.31%, and the AUC was 0.843. In the >6-year-old subgroup, the cutoff value of the LMR for predicting influenza A virus infection was 3.05, the sensitivity was 89.27%, the specificity was 89.61%, and the AUC was 0.949; the cutoff value of the LMR for predicting influenza B virus infection was 2.88, the sensitivity was 83.19%, the specificity was 92.21%, and the AUC was 0.924.Conclusions Routine blood tests are simple, inexpensive and easy to perform, and they are useful for the early identification of influenza virus infection in children. The LMR had the strongest predictive value for influenza virus infection in children older than 1 year, particularly influenza A virus infection.

scholarly journals Structural Basis for the Specific Neutralization of Stx2a with a Camelid Single Domain Antibody Fragment

Toxins ◽  
2018 ◽  
Vol 10 (3) ◽  
pp. 108 ◽  
Author(s):  
Robert Bernedo-Navarro ◽  
Ema Romão ◽  
Tomomasa Yano ◽  
Joar Pinto ◽  
Henri De Greve ◽  
...  
Keyword(s):  
Antibody Fragment ◽  
Single Domain ◽  
Structural Basis ◽  
Single Domain Antibody ◽  
Domain Antibody

scholarly journals Improved Antitumor Efficacy of Chimeric Antigen Receptor T Cells that Secrete Single-Domain Antibody Fragments

2020 ◽  
Vol 8 (4) ◽  
pp. 518-529 ◽  
Author(s):  
Yushu Joy Xie ◽  
Michael Dougan ◽  
Jessica R. Ingram ◽  
Novalia Pishesha ◽  
Tao Fang ◽  
...  
Keyword(s):  
T Cells ◽  
Chimeric Antigen Receptor ◽  
Antigen Receptor ◽  
Antibody Fragments ◽  
Single Domain ◽  
Antitumor Efficacy ◽  
Single Domain Antibody ◽  
Domain Antibody

scholarly journals Intracellular Expression of Camelid Single-Domain Antibodies Specific for Influenza Virus Nucleoprotein Uncovers Distinct Features of Its Nuclear Localization

2014 ◽  
Vol 89 (5) ◽  
pp. 2792-2800 ◽  
Author(s):  
Joseph Ashour ◽  
Florian I. Schmidt ◽  
Leo Hanke ◽  
Juanjo Cragnolini ◽  
Marco Cavallari ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Life Cycle ◽  
Nuclear Localization ◽  
Nuclear Import ◽  
Rna Viruses ◽  
Single Domain ◽  
Single Domain Antibody ◽  
Virus Life Cycle ◽  
Domain Antibody ◽  
Chemical Inhibition

ABSTRACTPerturbation of protein-protein interactions relies mostly on genetic approaches or on chemical inhibition. Small RNA viruses, such as influenza A virus, do not easily lend themselves to the former approach, while chemical inhibition requires that the target protein be druggable. A lack of tools thus constrains the functional analysis of influenza virus-encoded proteins. We generated a panel of camelid-derived single-domain antibody fragments (VHHs) against influenza virus nucleoprotein (NP), a viral protein essential for nuclear trafficking and packaging of the influenza virus genome. We show that these VHHs can target NP in living cells and perturb NP's function during infection. Cytosolic expression of NP-specific VHHs (αNP-VHHs) disrupts virus replication at an early stage of the life cycle. Based on their specificity, these VHHs fall into two distinct groups. Both prevent nuclear import of the viral ribonucleoprotein (vRNP) complex without disrupting nuclear import of NP alone. Different stages of the virus life cycle thus rely on distinct nuclear localization motifs of NP. Their molecular characterization may afford new means of intervention in the virus life cycle.IMPORTANCEMany proteins encoded by RNA viruses are refractory to manipulation due to their essential role in replication. Thus, studying their function and determining how to disrupt said function through pharmaceutical intervention are difficult. We present a novel method based on single-domain-antibody technology that permits specific targeting and disruption of an essential influenza virus protein in the absence of genetic manipulation of influenza virus itself. Characterization of such interactions may help identify new targets for pharmaceutical intervention. This approach can be extended to study proteins encoded by other viral pathogens.

Sign in / Sign up

Export Citation Format

Share Document