Regulation of host genome methylation and expression during HIV infection of T lymphocytes

Ph.D. ; It has been shown that both the methylation and gene expression play important roles in HIV-host interplay. In this study, to further investigate the relationship between HIV infection and patterns of genome-wide methylation and gene expression, we performed MeDIP-seq (Methylated DNA Immunoprecipitation Sequencing) and RNA-seq for two T lymphocyte cell lines. Each cell line contained HIV+ and control samples. ; Analysis of MeDIP-seq data revealed 3,060 hypo-methylated DMRs (Differentially methylated regions) and 2,659 hyper-methylated DMRs between HIV infected and uninfected cells. These DMRs were significantly enriched in some specific genomic regions including promoter, enhancer and gene body, suggesting that DNA methylation may play a role in HIV infection. Moreover, DMRs were able to determine the changing direction of methylation in these regions. Transcription factor binding motifs were also found to be significantly associated with methylation alterations, further suggesting that DNA methylation might influence the binding of transcription factors with DNA during HIV infection. As a support of this hypothesis, genes with promoter overlapping with DMRs were enriched into function categories related to transcription factor activities, including ‘transcription factor activity sequence’, ‘protein binding’ and ‘transcription factor binding’, etc. ; Analysis of RNA-seq data revealed 1,633 up-regulated genes and 2,124 down-regulated genes on average between HIV infected and uninfected cells. Results showed that, within the differential expressed genes, apoptosis related pathway, and primary immunodeficiency and immune response functional categories were significantly associated with altered gene expression after HIV-1 infection, suggesting that transcriptional regulation following HIV infection was closely related with T cell apoptosis and immune response. Encouragingly, these differential gene expression results were consistent with the findings from DNA methylation data, where HIV infection-associated ...