Hepatitis C Virus Escape Studies of Human Antibody AR3A Reveal a High Barrier to Resistance and Novel Insights on Viral Antibody Evasion Mechanisms.


Journal

Journal of virology
ISSN: 1098-5514
Titre abrégé: J Virol
Pays: United States
ID NLM: 0113724

Informations de publication

Date de publication:
15 02 2019
Historique:
received: 26 10 2018
accepted: 20 11 2018
pubmed: 30 11 2018
medline: 18 12 2019
entrez: 30 11 2018
Statut: epublish

Résumé

Yearly, ∼2 million people become hepatitis C virus (HCV) infected, resulting in an elevated lifetime risk for severe liver-related chronic illnesses. Characterizing epitopes of broadly neutralizing antibodies (NAbs), such as AR3A, is critical to guide vaccine development. Previously identified alanine substitutions that can reduce AR3A binding to expressed H77 envelope were introduced into chimeric cell culture-infectious HCV recombinants (HCVcc) H77(core-NS2)/JFH1. Substitutions G523A, G530A, and D535A greatly reduced fitness, and S424A, P525A, and N540A, although viable, conferred only low-level AR3A resistance. Using highly NAb-sensitive hypervariable region 1 (HVR1)-deleted HCVcc, H77/JFH1

Identifiants

pubmed: 30487284
pii: JVI.01909-18
doi: 10.1128/JVI.01909-18
pmc: PMC6364003
pii:
doi:

Substances chimiques

Antibodies, Monoclonal 0
Antibodies, Neutralizing 0
Antibodies, Viral 0
Epitopes 0
Viral Envelope Proteins 0
Viral Proteins 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : NIAID NIH HHS
ID : UM1 AI100663
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI106005
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI079031
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI123365
Pays : United States
Organisme : NIAID NIH HHS
ID : R56 AI106005
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI123861
Pays : United States

Informations de copyright

Copyright © 2019 American Society for Microbiology.

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Auteurs

Rodrigo Velázquez-Moctezuma (R)

Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases and Clinical Research Centre, Hvidovre Hospital, Hvidovre, and Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Andrea Galli (A)

Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases and Clinical Research Centre, Hvidovre Hospital, Hvidovre, and Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Mansun Law (M)

Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, California, USA.

Jens Bukh (J)

Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases and Clinical Research Centre, Hvidovre Hospital, Hvidovre, and Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark jbukh@sund.ku.dk jprentoe@sund.ku.dk.

Jannick Prentoe (J)

Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases and Clinical Research Centre, Hvidovre Hospital, Hvidovre, and Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark jbukh@sund.ku.dk jprentoe@sund.ku.dk.

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