Common Dysregulation of Innate Immunity Pathways in Human Primary Astrocytes Infected With Chikungunya, Mayaro, Oropouche, and Zika Viruses

Frontiers in Cellular and Infection Microbiology

Eurico de Arruda Neto¹  Jorge Paes Barreto Marcondes de Souza²  Soniza Vieira Alves-Leon²  Luciana Ferreira Romão³  Luan Pereira Diniz³  Camila Menezes Figueiredo⁴  Iranaia Assunção-Miranda⁴  Ana Paula de Campos Guimarães⁵  Alexandra Lehmkuhl Gerber⁵  Otávio José Bernardes Brustolini⁵  Ana Tereza Ribeiro de Vasconcelos⁵  Renan Pedra Souza⁶  Liliane Tavares de Faria Cavalcante⁷  Filipe Romero Rebello Moreira⁷  Amilcar Tanuri⁷  Fernando Luz de Castro⁷  Victor Emmanuel Viana Geddes⁸  Renato Santana de Aguiar⁸ 

[1] Departamento de Biologia Celular e Molecular, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil;Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil;Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil;Instituto de Microbiologia Paulo de Goes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil;Laboratório de Bioinformática, Laboratório Nacional de Computação Científica, Ministério de Ciência Tecnologia e Comunicações, Petrópolis, Brazil;Laboratório de Biologia Integrativa, Departamento de Genética Ecologia e Evolução, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil;Laboratório de Virologia Molecular, Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil;Laboratório de Virologia Molecular, Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil;Laboratório de Biologia Integrativa, Departamento de Genética Ecologia e Evolução, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil;

关键词: Chikungunya;    Mayaro;    Oropouche;    Zika;    innate immunity;    astrocytes;   

DOI  :  10.3389/fcimb.2021.641261

来源: Frontiers

【 摘 要 】

Arboviruses pose a major threat throughout the world and represent a great burden in tropical countries of South America. Although generally associated with moderate febrile illness, in more severe cases they can lead to neurological outcomes, such as encephalitis, Guillain-Barré syndrome, and Congenital Syndromes. In this context astrocytes play a central role in production of inflammatory cytokines, regulation of extracellular matrix, and control of glutamate driven neurotoxicity in the central nervous system. Here, we presented a comprehensive genome-wide transcriptome analysis of human primary astrocytes infected with Chikungunya, Mayaro, Oropouche, or Zika viruses. Analyses of differentially expressed genes (DEGs), pathway enrichment, and interactomes have shown that Alphaviruses up-regulated genes related to elastic fiber formation and N-glycosylation of glycoproteins, with down-regulation of cell cycle and DNA stability and chromosome maintenance genes. In contrast, Oropouche virus up-regulated cell cycle and DNA maintenance and condensation pathways while down-regulated extracellular matrix, collagen metabolism, glutamate and ion transporters pathways. Zika virus infection only up-regulated eukaryotic translation machinery while down-regulated interferon pathways. Reactome and integration analysis revealed a common signature in down-regulation of innate immune response, antiviral response, and inflammatory cytokines associated to interferon pathway for all arboviruses tested. Validation of interferon stimulated genes by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) corroborated our transcriptome findings. Altogether, our results showed a co-evolution in the mechanisms involved in the escape of arboviruses to antiviral immune response mediated by the interferon (IFN) pathway.

【 授权许可】

CC BY