Transcriptome Analysis Identifies Altered Biological Processes and Novel Markers in Human Immunodeficiency Virus-1...

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.

In this study, we obtained peripheral blood mononuclear cells from two LTNP subjects at multiple time points and performed RNA-sequencing analyses.

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.

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.