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KMID : 1144320210530030489
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감염과 화학요법
2021 Volume.53 No. 3 p.489 ~ p.502
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Transcriptome Analysis Identifies Altered Biological Processes and Novel Markers in Human Immunodeficiency Virus-1 Long-Term Non-Progressors
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Lee Da-Yeon
Yoon Cheol-Hee
Choi Sin-Young
Kim Jung-Eun
Cho Young-Keol
Choi Byeong-Sun
Park Ji-Hwan
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Abstract
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Background: The latent reservoir of Human Immunodificiency Virus-1 (HIV-1) has been a major barrier to the complete eradication of HIV-1 and the development of HIV therapy. Long-term non-progressors (LTNPs) are a rare group of patients with HIV-1 who can spontaneously control HIV-1 replication without antiretroviral therapy. Transcriptome analysis is necessary to predict the pathways involved in the natural control of HIV-1, elucidate the mechanisms involved in LTNPs, and find biomarkers for HIV-1 reservoir therapy.
Materials and Methods: In this study, we obtained peripheral blood mononuclear cells from two LTNP subjects at multiple time points and performed RNA-sequencing analyses.
Results: We found that LTNPs and normal subjects had different transcriptome profiles. Functional annotation analysis identified that differentially expressed genes in LTNPs were enriched in several biological pathways such as cell cycle-related pathways and the transforming growth factor-beta signaling pathway. However, genes that were downregulated in LTNPs were associated with immune responses such as the interferon response and IL2-STAT5 signaling. Protein-protein interaction network analysis showed that CD8A, KLRD1, ASGR1, and MLKL, whose gene expression was upregulated in LTNPs, directly interacted with HIV-1 proteins. The network analysis also found that viral proteins potentially regulated host genes that were associated with immune system processes, metabolic processes, and gene expression regulation.
Conclusion: Our longitudinal transcriptome analysis of the LTNPs identified multiple previously undescribed pathways and genes that may be useful in the discovery of novel therapeutic targets and biomarkers.
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KEYWORD
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Human immunodeficiency virus, HIV-1 non-progressors, RNA-seq, Gene expression, Transcriptome analysis
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