MyD88 signalling in B cells and antibody responses during Oropouche virus-induced neurological disease in mice
Year: 2025
Type: article
Abstract: Background 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 + Ifnar fl , and CD19 -Cre + MyD88 fl 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 + MyD88 fl mice but not CD19 -Cre + Ifnar fl 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 + MyD88 fl 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 + MyD88 fl 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. Funding São Paulo Research Foundation (FAPESP), National Council for Scientific and Technological Development (CNPq), Coordination for the Improvement of Higher Education Personnel (CAPES), Unicamp Research Affairs Office, PIPAE University of São Paulo, Wellcome Trust, and National Institute of Science and Technology on Photonics Applied to Cell Biology (INFABIC, Unicamp).
Source: EBioMedicine
Authors: Daniel Augusto Toledo-Teixeira, Pierina Lorencini Parise, Bruno Brito Pereira da Silva, Camila Lopes Simeoni, Aline Vieira, Julia Forato, Matheus Cavalheiro Martini, Mariene Ribeiro Amorim, Karina Bispo-dos-Santos, Natália Silva Brunetti, Gabriela Fabiano de Souza, Lais Durço Coimbra, Marina Alves Fontoura, Stéfanie Primon Muraro, Priscilla Paschoal Barbosa, Valquíria Aparecida Matheus, Xinyi Hua, Pedro Manoel Mendes de Moraes Vieira, Fabiana Granja, Pritesh Lalwani, Marco Aurélio Ramirez Vinolo, Guilherme Paier Milanez, Rafael Elias Marques, Ceri Alan Fielding, William Marciel de Souza, Alessandro dos Santos Farias, David Anthony Price, Michael Steven Diamond, Eduardo Lani Volpe Silveira, José Luiz Proenca-Modena
Institutions: Universidade Estadual de Campinas (UNICAMP), Brazilian Center for Research in Energy and Materials, Brazilian Biosciences National Laboratory, University of Kentucky, Universidade Federal de Roraima, Fundação Oswaldo Cruz, University Hospital of Wales, Cardiff University, Washington University in St. Louis, Universidade de São Paulo
Language: English
Topic: Viral Infections and Vectors
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,780
Funders: Helsingin Yliopisto, Wellcome Trust, Fundação de Amparo à Pesquisa do Estado de São Paulo, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Universidade de São Paulo, Fundo de Apoio ao Ensino, à Pesquisa e Extensão, Universidade Estadual de Campinas, National Institute of Allergy and Infectious Diseases
Awards: G1048651249, Identification of B cell protective antigens/epitopes against asexual and sexual blood forms of Plasmodium parasites through monoclonal antibodies, G1207639193, G1626936955, G2319661392, G2343365992, World Reference Center for Emerging Viruses and Arboviruses (WRCEVA), G2607969177, G2823776494, Pathogenesis and neurovirulence of emerging viruses in Brazil, G3135932678, G3285709688, G4042370543, G4941087670, G5177801762, G5272573338, G5512256782, G6191138830, G6449457889, G6537414629, G686464296, G7322204840, G7725770629, ARBOVERSE, a data-driven platform and disease modeling to anticipating and mitigating arbovirus emergence, G8045151581, G957840319
OpenAlex ID: W4411442477