Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Nov 12;14(11):2505.
doi: 10.3390/v14112505.

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

Fernando Luz de Castro  1 , Otávio José Bernandes Brustolini  2 , Victor Emmanuel Viana Geddes  3 , Jorge Paes Barreto Marcondes de Souza  4 , Soniza Vieira Alves-Leon  5 , Renato Santana Aguiar  1   3 , Ana Tereza Ribeiro Vasconcelos  2
Affiliations

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

Fernando Luz de Castro et al. Viruses. .

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.

Keywords: arboviruses; astrocytes; human endogenous retroviruses.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Modulation of HERVs’ expression in human primary astrocytes infected with ChikV, MayV, OroV, and ZikV. (A) The number of differentially expressed HERVs comparing the induced (upregulated) and suppressed (downregulated) HERVs by the four viruses. (B) Dispersion of the HERVs comparing the log2FC and significance (−log10(q-value)). The red dots indicate the accepted differentially expressed HERVs up to log2FC > 1 and adjusted p-value < 0.05. (C) Specific co-regulation of HERVs by the four viruses ChikV, MayV, OroV, and ZikV.
Figure 2
Figure 2
Enriched families of the differentially expressed HERVs by the arboviruses (ChikV, MayV, OroV, and ZikV). (A) Upregulated and (B) downregulated HERVs families.
Figure 3
Figure 3
Genome positions and cellular pathways of nearby genes co-modulated by alphaviruses in human primary astrocytes cells. (A) Frequencies of the genes co-modulated by HERVs expressed through genomic position in kilobase pairs (KBP) in the alphavirus infections. (B) The most enriched GO categories of the nearest genes related to HERVs’ induction by alphaviruses.
Figure 4
Figure 4
Networks of protein–protein interaction of DEGs related to the DEHERVs nearby genes. (A) ChikV; (B) MayV; (C) OroV.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Meyer T.J., Rosenkrantz J.L., Carbone L., Chavez S.L. Endogenous Retroviruses: With Us and against Us. Front. Chem. 2017;5:23. doi: 10.3389/fchem.2017.00023. - DOI - PMC - PubMed
    1. Cullen H., Schorn A.J. Endogenous Retroviruses Walk a Fine Line between Priming and Silencing. Viruses. 2020;12:792. doi: 10.3390/v12080792. - DOI - PMC - PubMed
    1. Jin X., Xu X.-E., Jiang Y.-Z., Liu Y.-R., Sun W., Guo Y.-J., Ren Y.-X., Zuo W.-J., Hu X., Huang S.-L., et al. The Endogenous Retrovirus-Derived Long Noncoding RNA TROJAN Promotes Triple-Negative Breast Cancer Progression via ZMYND8 Degradation. Sci. Adv. 2019;5:eaat9820. doi: 10.1126/sciadv.aat9820. - DOI - PMC - PubMed
    1. Fu B., Ma H., Liu D. Endogenous Retroviruses Function as Gene Expression Regulatory Elements during Mammalian Pre-Implantation Embryo Development. IJMS. 2019;20:790. doi: 10.3390/ijms20030790. - DOI - PMC - PubMed
    1. Zhou B., Qi F., Wu F., Nie H., Song Y., Shao L., Han J., Wu Z., Saiyin H., Wei G., et al. Endogenous Retrovirus-Derived Long Noncoding RNA Enhances Innate Immune Responses via Derepressing RELA Expression. mBio. 2019;10 doi: 10.1128/mBio.00937-19. - DOI - PMC - PubMed

Publication types