MyD88 signalling in B cells and antibody responses during Oropouche virus-induced neurological disease in mice

Toledo-Teixeira, Daniel Augusto, Parise, Pierina Lorencini, Pereira da Silva, Bruno Brito, Simeoni, Camila Lopes, Vieira, Aline, Forato, Julia, Martini, Matheus Cavalheiro, Amorim, Mariene Ribeiro, Bispo-dos-Santos, Karina, Brunetti, Natália Silva, Fabiano de Souza, Gabriela, Coimbra, Lais Durço, Fontoura, Marina Alves, Muraro, Stéfanie Primon, Barbosa, Priscilla Paschoal, Matheus, Valquíria Aparecida, Hua, Xinyi, Mendes de Moraes Vieira, Pedro Manoel, Granja, Fabiana, Lalwani, Pritesh, Ramirez Vinolo, Marco Aurélio, Milanez, Guilherme Paier, Marques, Rafael Elias, Fielding, Ceri Alan ORCID: https://orcid.org/0000-0002-5817-3153, Marciel de Souza, William, Farias, Alessandro dos Santos, Price, David Anthony ORCID: https://orcid.org/0000-0001-9416-2737, Diamond, Michael Steven, Silveira, Eduardo Lani Volpe and Proenca-Modena, José Luiz 2025. MyD88 signalling in B cells and antibody responses during Oropouche virus-induced neurological disease in mice. EBioMedicine , 105815. 10.1016/j.ebiom.2025.105815

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Abstract

ackground Oropouche virus (OROV) is a neglected insect-borne orthobunyavirus that causes a febrile illness, neurological disease, and pregnancy complications in humans across an endemic area spanning South and Central America. The host factors associated with disease pathogenesis have nonetheless remained obscure, and little is known about the immune determinants of protection against OROV. Methods We tracked morbidity, mortality, viral loads, and serum neutralisation in wild-type (WT), Rag1−/−, CD19-Cre+Ifnarfl, and CD19-Cre+MyD88fl mice and performed immunophenotyping experiments, passive serum transfers, and adoptive cell transfers to determine how early antibody responses and B cell subsets control viral replication and dissemination to the central nervous system after infection with OROV. Findings In line with a protective role for B cells, WT mice efficiently produced OROV-specific antibodies within 6 days of infection. Serum transfer containing neutralising IgM from WT to Rag1−/− mice prevented neurological disease in OROV-challenged mice. CD19-Cre+MyD88fl mice but not CD19-Cre+Ifnarfl mice were vulnerable to neurological disease and produced lower titres of OROV-specific antibodies that exhibited suboptimal neutralisation and potency compared with MyD88-sufficient mice. CD19-Cre+MyD88fl mice also presented with reduced numbers of marginal zone B (MZB) cells and plasmablasts after infection, which were associated with high viral burdens and lethality. Adoptive transfer of MZB cells from WT mice protected CD19-Cre+MyD88fl mice and partially protected Rag1−/− mice from lethal infection with OROV. Interpretation Early MyD88 signalling in B cells is required for optimal antibody responses that limit viral replication and neurological disease in mice infected with OROV.

Item Type:	Article
Date Type:	Published Online
Status:	In Press
Schools:	Schools > Medicine
Publisher:	Elsevier
ISSN:	2352-3964
Date of First Compliant Deposit:	1 July 2025
Date of Acceptance:	5 June 2025
Last Modified:	01 Jul 2025 11:15
URI:	https://orca.cardiff.ac.uk/id/eprint/179399

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