Modulation of HERV Expression by Four Different Encephalitic Arboviruses during Infection of Human Primary Astrocytes

Abstract

Human retroelements (HERVs) are retroviral origin sequences fixed in the human genome. HERVs induction is associated with neurogenesis, cellular development, immune activation, and neurological disorders. Arboviruses are often associated with the development of encephalitis. The interplay between these viruses and HERVs has not been fully elucidated. In this work, we analyzed RNAseq data derived from infected human primary astrocytes by Zika (ZikV), Mayaro (MayV), Oropouche (OroV) and Chikungunya (ChikV) viruses, and evaluated the modulation of HERVs and their nearby genes. Our data show common HERVs expression modulation by both alphaviruses, suggesting conserved evolutionary routes of transcription regulation. A total of 15 HERVs were co-modulated by the four arboviruses, including the highly upregulated HERV4_4q22. Data on the upregulation of genes nearby to these elements in ChikV, MayV and OroV infections were also obtained, and interaction networks were built. The upregulation of 14 genes common among all viruses was observed in the networks, and 93 genes between MayV and ChikV. These genes are related to cellular processes such as cellular replication, cytoskeleton, cell vesicle traffic and antiviral response. Together, our results support the role of HERVs induction in the transcription regulation process of genes during arboviral infections.