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bioRxiv · 10.1101/606731

CD4 T-cell transcriptome expression reversal of the lncRNA-mRNA co-expression network in elite controller vs. normal-process HIV patients

Chen, C.·Lu, X.·Wu, N.
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Abstract

Elite controller refers to a patient with human imunodeficienvcy virus infection with an undetected viral load without anti-viral treatment. Studies on gene expression and regulation in these individuals are limited but significant. We enrolled 196 patients and collected CD4 T-cell samples from two elite controllers, two normal-process infected patients, and two healthy controls to perform second-generation transcriptome sequencing. Using the Cuffdiff model, we identified differentially expressed mRNAs and long non-coding RNAs with corrected P value < 0.05, and constructed a protein-protein interaction network as well a long non-coding RNA-mRNA co-expression network based on the Pearson correlation coefficient. Interestingly, some interactions within the networks were identified as associated with viral infections and immune responses. This was the first study to examine gene transcription in elite controllers and to study their functional relationships. Our results provide a reference for subsequent functional verification at the molecular or cellular level.\n\nAuthor SummarySome individuals can spontaneously inhibit HIV replication after infection with HIV, and thus lack any symptoms. Studies on these patients, termed elite controllers (ECs) will help researchers and clinicians to understand the interrelationship between HIV and the host. In the present study, we focused on the interactions and functional relationships between significantly differentially expressed long non-coding RNAs (lncRNAs) and mRNAs in ECs vs. normal-process patients (NPs). RNA-sequencing was performed for six representative samples of CD4 T-cells. Using the Pearson correlation test, an lncRNA-mRNA co-expression network was constructed. Several new regulatory relationships between transcripts were revealed that might be closely related to the ability of ECs to maintain a low viral load for long periods without anti-viral treatment. For example, lncRNA C3orf35 was upregulated in ECs vs. NPs and was positively related to downregulation of GNG2 mRNA (encoding G protein subunit gamma 2), which functions in chemokine signaling pathways and HIV-1 infection. Overall, we identified certain interesting genetic interactions that will provide information about the mechanism of host suppression of viral replication.

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Chen, C., Lu, X., Wu, N.. 2019-04-11. CD4 T-cell transcriptome expression reversal of the lncRNA-mRNA co-expression network in elite controller vs. normal-process HIV patients. https://doi.org/10.1101/606731

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