Autor: |
Ribeiro Amorim M; Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas 13083-862, Brazil., Cornejo Pontelli M; Department of Cell Biology and Virology Research Center, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, Brazil., Fabiano de Souza G; Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas 13083-862, Brazil., Primon Muraro S; Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas 13083-862, Brazil., de Toledo-Teixeira DA; Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas 13083-862, Brazil., Forato J; Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas 13083-862, Brazil., Bispo-Dos-Santos K; Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas 13083-862, Brazil., Barbosa NS; Department of Cell Biology and Virology Research Center, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, Brazil., Cavalheiro Martini M; Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas 13083-862, Brazil., Lorencini Parise P; Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas 13083-862, Brazil., Vieira A; Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas 13083-862, Brazil., Paier Milanez G; Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas 13083-862, Brazil., Lamberti Pinto daSilva L; Department of Cell Biology and Virology Research Center, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, Brazil., Jaychand Lalwani P; Leônidas and Maria Deane Institute (ILMD), Fiocruz Amazônia, Manaus 69057-070, Brazil., Santos Farias A; Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas 13083-862, Brazil., Ramirez Vinolo MA; Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas 13083-862, Brazil., Sesti-Costa R; Hematology and Hemotherapy Center, Medical School of the University of Campinas, Campinas 13083-887, Brazil., Arruda E; Department of Cell Biology and Virology Research Center, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, Brazil., Proenca-Modena JL; Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas 13083-862, Brazil. |
Abstrakt: |
Oropouche orthobunyavirus (OROV) is an emerging arbovirus with a high potential of dissemination in America. Little is known about the role of peripheral blood mononuclear cells (PBMC) response during OROV infection in humans. Thus, to evaluate human leukocytes susceptibility, permissiveness and immune response during OROV infection, we applied RNA hybridization, qRT-PCR and cell-based assays to quantify viral antigens, genome, antigenome and gene expression in different cells. First, we observed OROV replication in human leukocytes lineages as THP-1 monocytes, Jeko-1 B cells and Jurkat T cells. Interestingly, cell viability and viral particle detection are maintained in these cells, even after successive passages. PBMCs from healthy donors were susceptible but the infection was not productive, since neither antigenome nor infectious particle was found in the supernatant of infected PBMCs. In fact, only viral antigens and small quantities of OROV genome were detected at 24 hpi in lymphocytes, monocytes and CD11c + cells. Finally, activation of the Interferon (IFN) response was essential to restrict OROV replication in human PBMCs. Increased expression of type I/III IFNs, ISGs and inflammatory cytokines was detected in the first 24 hpi and viral replication was re-established after blocking IFNAR or treating cells with glucocorticoid. Thus, in short, our results show OROV is able to infect and remain in low titers in human T cells, monocytes, DCs and B cells as a consequence of an effective IFN response after infection, indicating the possibility of leukocytes serving as a trojan horse in specific microenvironments during immunosuppression. |