Transcriptome sequencing of neurologic diseases associated genes in HHV-6A infected human astrocyte

Abstract

Human Herpesvirus 6 (HHV-6) has been involved in the development of several central nervous system (CNS) diseases, such as Alzheimer's disease, multiple sclerosis and glioma. In order to identify the pathogenic mechanism of HHV-6A infection, we carried out mRNA-seq study of human astrocyte HA1800 cell with HHV-6A GS infection. Using mRNA-seq analysis of HA1800-control cells with HA1800-HHV-6A GS cells, we identified 249 differentially expressed genes. After investigating these candidate genes, we found seven genes associated with two or more CNS diseases: CTSS, PTX3, CHI3L1, Mx1, CXCL16, BIRC3, and BST2. This is the first transcriptome sequencing study which showed the significant association of these genes between HHV-6A infection and neurologic diseases. We believe that our findings can provide a new perspective to understand the pathogenic mechanism of HHV-6A infection and neurologic diseases.

Keywords: HHV-6; astrocyte; neurologic diseases; transcriptome sequencing study.

Figure 1. Differentially expressed genes (DEGs) enriched and identified by GO analyses

A. The expression of cellular genes in two enriched populations of HA1800-control and HA1800-HHV6GS cells for 24 h were assessed using mRNA-seq. The distribution of genes with a change in expression of false discovery rate (FDR) < 0.1 is shown in red on the MA plot (log total counts versus log fold-change). B. The biological processes of the DEGs were identified by GO analyses. C. The cellular components of the DEGs were identified by GO analyses. D. The molecular functions of the DEGs were identified by GO analyses.

Figure 2. Differentially expressed genes associated pathways analysis

Differentially expressed genes associated pathways were analyzed by GO and KEGG pathway tools.

Figure 3. Differentially expressed genes associated CNS diseases analysis

Differentially expressed genes associated CNS diseases were analyzed by DAVID functional annotation chart tool.

Figure 4. Predicted interaction networks of genes differentially expressed during HHV-6A infection

Differentially expressed genes are depicted: links have been predicted using STRING (http://string.embl.de/). Predicted interactions are depicted according to the type of available evidence. The interactions (see color labels) include direct (physical) and indirect (functional) associations; they are derived from four sources: genomic context, high-throughput experiments, conserved coexpression, and previous knowledge from literature.