Show simple item record

dc.contributor.authorKoromyslova, AD
dc.contributor.authorHansman, GS
dc.date.accessioned2021-08-18T03:52:19Z
dc.date.available2021-08-18T03:52:19Z
dc.date.issued2017
dc.identifier.issn1553-7374
dc.identifier.doi10.1371/journal.ppat.1006636
dc.identifier.urihttp://hdl.handle.net/10072/407043
dc.description.abstractNorovirus is the leading cause of gastroenteritis worldwide. Despite recent developments in norovirus propagation in cell culture, these viruses are still challenging to grow routinely. Moreover, little is known on how norovirus infects the host cells, except that histo-blood group antigens (HBGAs) are important binding factors for infection and cell entry. Antibodies that bind at the HBGA pocket and block attachment to HBGAs are believed to neutralize the virus. However, additional neutralization epitopes elsewhere on the capsid likely exist and impeding the intrinsic structural dynamics of the capsid could be equally important. In the current study, we investigated a panel of Nanobodies in order to probe functional epitopes that could trigger capsid rearrangement and/ or interfere with HBGA binding interactions. The precise binding sites of six Nanobodies (Nano-4, Nano-14, Nano-26, Nano-27, Nano-32, and Nano-42) were identified using X-ray crystallography. We showed that these Nanobodies bound on the top, side, and bottom of the norovirus protruding domain. The impact of Nanobody binding on norovirus capsid morphology was analyzed using electron microscopy and dynamic light scattering. We discovered that distinct Nanobody epitopes were associated with varied changes in particle structural integrity and assembly. Interestingly, certain Nanobody-induced capsid morphological changes lead to the capsid protein degradation and viral RNA exposure. Moreover, Nanobodies employed multiple inhibition mechanisms to prevent norovirus attachment to HBGAs, which included steric obstruction (Nano-14), allosteric interference (Nano-32), and violation of normal capsid morphology (Nano-26 and Nano-85). Finally, we showed that two Nanobodies (Nano-26 and Nano-85) not only compromised capsid integrity and inhibited VLPs attachment to HBGAs, but also recognized a broad panel of norovirus genotypes with high affinities. Consequently, Nano-26 and Nano-85 have a great potential to function as novel therapeutic agents against human noroviruses.
dc.description.peerreviewedYes
dc.languageEnglish
dc.publisherPUBLIC LIBRARY SCIENCE
dc.relation.ispartofpagefrome1006636
dc.relation.ispartofissue11
dc.relation.ispartofjournalPLoS Pathog
dc.relation.ispartofvolume13
dc.subject.fieldofresearchMicrobiology
dc.subject.fieldofresearchImmunology
dc.subject.fieldofresearchMedical microbiology
dc.subject.fieldofresearchcode3107
dc.subject.fieldofresearchcode3204
dc.subject.fieldofresearchcode3207
dc.subject.keywordsScience & Technology
dc.subject.keywordsLife Sciences & Biomedicine
dc.subject.keywordsMicrobiology
dc.subject.keywordsParasitology
dc.titleNanobodies targeting norovirus capsid reveal functional epitopes and potential mechanisms of neutralization
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationKoromyslova, AD; Hansman, GS, Nanobodies targeting norovirus capsid reveal functional epitopes and potential mechanisms of neutralization, PLoS Pathog, 2017, 13 (11), pp. e1006636
dcterms.dateAccepted2017-09-08
dcterms.licensehttp://creativecommons.org/licenses/by/4.0/
dc.date.updated2021-08-17T22:25:40Z
dc.description.versionVersion of Record (VoR)
gro.rights.copyright© 2017 Koromyslova, Hansman. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
gro.hasfulltextFull Text
gro.griffith.authorHansman, Grant S.


Files in this item

This item appears in the following Collection(s)

  • Journal articles
    Contains articles published by Griffith authors in scholarly journals.

Show simple item record