Distinct transcriptomic profiles of naive CD4+T cells distinguish HIV-1 infected patients initiating antiretroviral therapy at acute or chronic phase of infection

We analyzed the whole transcriptome characteristics of blood CD4+ T naive (T-N) cells isolated from HIV-1 infected patients starting ART at acute (early ART = EA; n = 13) or chronic (late ART = LA; n = 11) phase of infection and controls (C; n = 15). RNA sequencing revealed 389 differentially expressed genes (DEGs) in EA and 810 in LA group in relation to controls. Comparison of the two groups of patients showed 183 DEGs. We focused on DEGs involved in apoptosis, inflammation and immune response. Clustering showed a poor separation of EA from C suggesting that these two groups present a similar transcriptomic profile of CD4+ T-N cells. The comparison of EA and LA patients resulted in a high cluster purity revealing that different biological dysfunctions characterize EA and LA patients. The upregulated expression of several inflammatory chemokine genes distinguished the patient groups from C; CCL2 and CCL7, however, were downregulated in EA compared to LA patients. BCL2, an anti-apoptotic factor pivotal for naive T cell homeostasis, distinguished both EA and LA from C. The expression of several DEGs involved in different inflammatory processes (TLR4, PTGS2, RAG1, IFNA16) was lower in EA compared LA. We conclude that although the transcriptome of CD4+ T-N cells isolated from patients initiating ART at acute infection reveals a more quiescent phenotype, the survival profile of these cells still appears to be affected. Our results show that the detrimental process of inflammation is under more efficient control in EA patients.

Automated summary

The study analyzed the transcriptome characteristics of blood CD4+ T naive cells from HIV-1 infected patients starting ART at acute infection, revealing a more efficiently controlled inflammation process in early ART patients, but with still affected cell survival profile.