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Afridi, S.Q. ; Usman, Z.* ; Donakonda, S.* ; Wettengel, J.M. ; Velkov, S. ; Beck, R.* ; Gerhard, M.* ; Knolle, P.* ; Frishman, D.* ; Protzer, U. ; Moeini, H. ; Hoffmann, D.

Prolonged norovirus infections correlate to quasispecies evolution resulting in structural changes of surface-exposed epitopes.

iScience 24, 102802:102802 (2021)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
In this study, we analyzed norovirus (NoV) evolution in sequential samples of six chronically infected patients. The capsid gene was amplified from stool samples, and deep sequencing was performed. The role of amino acid flexibility in structural changes and ligand binding was studied with molecular dynamics (MD) simulations. Concentrations of capsid-specific antibodies increased in sequential sera. Capsid sequences accumulated mutations during chronic infection, particularly in the surface-exposed antigenic epitopes A, D, and E. The number of quasispecies increased in infections lasting for >1 month. Interestingly, high genetic complexity and distances were followed by ongoing NoV replication, whereas lower genetic complexity and distances preceded cure. MD simulation revealed that surface-exposed amino acid substitutions of the P2 domain caused fluctuation of blockade epitopes. In conclusion, the capsid protein accumulates numerous mutations during chronic infection; however, only those on the protein surface change the protein structure substantially and may lead to immune escape.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Molecular Modeling ; Virology; Gii.4; Protection; Emergence
ISSN (print) / ISBN 2589-0042
e-ISSN 2589-0042
Zeitschrift iScience
Quellenangaben Band: 24, Heft: 7, Seiten: 102802 Artikelnummer: 102802 Supplement: ,
Verlag Elsevier
Verlagsort Amsterdam ; Bosten ; London ; New York ; Oxford ; Paris ; Philadelphia ; San Diego ; St. Louis
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Virology (VIRO)
Förderungen German Center for Infection Research (DZIF)
German Academic Exchange Service (DAAD)