Abstract
Influenza is a contagious acute respiratory disease caused by the influenza virus infection. Hemagglutinin (HA) is an important target in the therapeutic treatment and diagnostic detection of the influenza virus. Influenza A virus encompasses several different HA subtypes with different strains, which are constantly changing. In this study, we identified a fully human H1N1 neutralizing antibody (32D6) via an Epstein-Barr virus-immortalized B cell-based technology. 32D6 specifically neutralizes the clinically isolated H1N1 strains after the 2009 pandemic but not the earlier strains. The epitope was identified through X-ray crystallographic analysis of the 32D6-Fab/HA1 complex structure, which revealed a unique loop conformation located on the top surface of HA. The major region is composed of two peptide segments (residues 172–177 and 206–213), which form an abreast loop conformation. The residue T262 between the two loops forms a conformational epitope for recognition by 32D6. Three water molecules were observed at the interface of HA and the heavy chain, and they may constitute a stabilizing element for the 32D6-HA association. In addition, each 32D6-Fab is likely capable of blocking one HA trimer. This study provides important information on the strain specificity of 32D6 for the therapeutic treatment and detection of viral infection.
Highlights
Influenza A viruses are divided into subtypes based on two proteins on the viral surface: the hemagglutinin (HA) and the neuraminidase (NA)
The confirmed cases of influenza infection can be treated with both zanamivir and oseltamivir, and if administered within 36 to 48 h of the onset of clinical symptoms, both drugs reduce the duration of illness by 1–1.5 days in patients of all ages
Patients infected with baloxavir-resistant viruses exhibited prolonged virus shedding, and the median time to symptom alleviation was longer in baloxavir recipients infected with viruses bearing these substitutions than in those infected with viruses that lacked these substitutions[7,10]
Summary
Influenza A viruses are divided into subtypes based on two proteins on the viral surface: the hemagglutinin (HA) and the neuraminidase (NA). Antigenic shift can be the result of a direct jump from an unknown animal strain to humans or a reassortment of two or more influenza viruses within the same cell It results in a new virus with the HA or the HA-NA combination that has emerged from an animal population so different from the same subtype in humans that most people do not have immunity to the new virus. Most influenza virus-neutralizing antibodies, elicited via vaccination or infection, bind to the globular head of HA and block the interaction between the viral sialic acid receptors and the host cells. We identified a human anti-H1N1 (influenza A virus A/ California/7/2009 NYMCX-179A) neutralizing antibody via an Epstein-Barr virus (EBV)-immortalized B cell-based technology It interacts with the HA head portion of H1N1 after 2009. We further characterized the mode of binding by analyzing the complex crystal structure of the fragment for antigen-binding (Fab) and the antigen
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
