Table_4_Common Dysregulation of Innate Immunity Pathways in Human Primary Astrocytes Infected With Chikungunya, Mayaro, Oropouche, and Zika Viruses.xlsx (28.01 kB)
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Table_4_Common Dysregulation of Innate Immunity Pathways in Human Primary Astrocytes Infected With Chikungunya, Mayaro, Oropouche, and Zika Viruses.xlsx

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posted on 15.03.2021, 05:23 by Victor Emmanuel Viana Geddes, Otávio José Bernardes Brustolini, Liliane Tavares de Faria Cavalcante, Filipe Romero Rebello Moreira, Fernando Luz de Castro, Ana Paula de Campos Guimarães, Alexandra Lehmkuhl Gerber, Camila Menezes Figueiredo, Luan Pereira Diniz, Eurico de Arruda Neto, Amilcar Tanuri, Renan Pedra Souza, Iranaia Assunção-Miranda, Soniza Vieira Alves-Leon, Luciana Ferreira Romão, Jorge Paes Barreto Marcondes de Souza, Ana Tereza Ribeiro de Vasconcelos, Renato Santana de Aguiar

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.

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