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TitleHuman mAbs Broadly Protect against Arthritogenic Alphaviruses by Recognizing Conserved Elements of the Mxra8 Receptor-Binding Site.
Journal, issue, pagesCell Host Microbe, Vol. 28, Issue 5, Page 699-711.e7, Year 2020
Publish dateNov 11, 2020
AuthorsLaura A Powell / Andrew Miller / Julie M Fox / Nurgun Kose / Thomas Klose / Arthur S Kim / Robin Bombardi / Rashika N Tennekoon / A Dharshan de Silva / Robert H Carnahan / Michael S Diamond / Michael G Rossmann / Richard J Kuhn / James E Crowe /
PubMed AbstractMosquito inoculation of humans with arthritogenic alphaviruses results in a febrile syndrome characterized by debilitating musculoskeletal pain and arthritis. Despite an expanding global disease ...Mosquito inoculation of humans with arthritogenic alphaviruses results in a febrile syndrome characterized by debilitating musculoskeletal pain and arthritis. Despite an expanding global disease burden, no approved therapies or licensed vaccines exist. Here, we describe human monoclonal antibodies (mAbs) that bind to and neutralize multiple distantly related alphaviruses. These mAbs compete for an antigenic site and prevent attachment to the recently discovered Mxra8 alphavirus receptor. Three cryoelectron microscopy structures of Fab in complex with Ross River (RRV), Mayaro, or chikungunya viruses reveal a conserved footprint of the broadly neutralizing mAb RRV-12 in a region of the E2 glycoprotein B domain. This mAb neutralizes virus in vitro by preventing virus entry and spread and is protective in vivo in mouse models. Thus, the RRV-12 mAb and its defined epitope have potential as a therapeutic agent or target of vaccine design against multiple emerging arthritogenic alphavirus infections.
External linksCell Host Microbe / PubMed:32783883 / PubMed Central
MethodsEM (single particle)
Resolution4.8 - 6.33 Å
Structure data

EMDB-21473, PDB-6vyv:
Human mAbs broadly protect against infection of arthritiogenic alphaviruses by recognizing conserved elements of the MXR8 receptor binding domain
Method: EM (single particle) / Resolution: 6.33 Å

EMDB-21496, PDB-6w09:
Human mAbs broadly protect against infection of arthritiogenic alphaviruses by recognizing conserved elements of the MXR8 receptor binding domain
Method: EM (single particle) / Resolution: 5.3 Å

EMDB-21509, PDB-6w1c:
Human mAbs broadly protect against infection of arthritiogenic alphaviruses by recognizing conserved elements of the MXR8 receptor binding domain
Method: EM (single particle) / Resolution: 5.3 Å

EMDB-21532: Native Mayaro virus cryo EM map, resolution 4.8 Angstroms
PDB-6w2u: Mayaro Virus glycoprotein E1 ectodomain and glycoportien E2 ectodomain asymmetric unit
Method: EM (single particle) / Resolution: 4.8 Å

Source
  • ross river virus (strain t48)
  • homo sapiens (human)
  • chikungunya virus
  • mayaro virus (strain brazil)
  • Mayaro virus
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / virus / monoclonal antibody / complex / VIRAL PROTEIN-IMMUNE SYSTEM complex / VIRUS/IMMUNE SYSTEM / VIRUS-IMMUNE SYSTEM complex

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