Signature genes associated with immunological non-responsiveness to anti-retroviral therapy in HIV-1 subtype-c infection

• Published in: PloS one 2020-06, Vol.15 (6), p.e0234270-e0234270
• Main Authors: Singh, Sukhvinder, Toor, Jaideep S, Sharma, Aman, Arora, Sunil K
• Format: Article
• Language: English
• Subjects: Acquired immune deficiency syndrome; AIDS; Analysis; Antiretroviral drugs; Antiretroviral therapy; Apoptosis; Biology and Life Sciences; Care and treatment; CD4 antigen; CD4 lymphocytes; Cell activation; Cytokines; DNA microarrays; Foxp3 protein; Gene expression; Gene regulation; Genes; Genetic aspects; Health aspects; Highly active antiretroviral therapy; HIV; HIV infections; Homeostasis; Human immunodeficiency virus; IL-1β; Immune response; Immunology; Infections; Inflammation; Internal medicine; Lymphocytes; Lymphocytes T; Medical education; Medicine and Health Sciences; Molecular modelling; Mortality; Patient outcomes; Peripheral blood; Protein interaction; Proteins; Research and Analysis Methods; Statistical analysis; Therapy; Tumor necrosis factor-α
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0234270

HIV-infected individuals undergoing therapy may show an immunological-discordant response to therapy, with poor CD4.sup.+ T cells recovery, despite viral suppression below the detection limit. The present study was carried out to delineate the underlying molecular mechanisms of immunological non-responsiveness to HIV therapy. We conducted microarray-based whole gene expression profiles of 30 subjects infected with HIV-1 subtype C, in peripheral blood to discern the signature genes associated with immunological non-responsiveness. After a thorough analysis and comparison of gene-expression profiles, microarray data was validated via qRT-PCR approach. Overall, we found 10 genes significantly up-regulated and 60 genes down-regulated ([greater than or equal to]2-fold change) in immunological non-responders as compared to responders. Based on these results and pathway analysis of the protein-protein interaction, 20 genes were shortlisted for validation in human infected cases. We found statistically significant differences in expression levels of twelve genes IL-1[alpha], IL-1[beta], IL-7R, TNF-[alpha], FoxP3, PDCD5, COX7B, SOCS1, SOCS3, RPL9, RPL23, and LRRN3 respectively among immunological non-responders compared to therapy responders, confirming their an intimate relationship with immunological responsiveness to therapy. Altogether, microarray and qRT-PCR validation results indicated that the aberrant expression of key genes involved in the regulation of T cell homeostasis, immune activation, inflammatory cytokine production, apoptosis, and immune-regulatory processes are possibly associated with immunological non-responsiveness in HIV-1 C infected individuals on ART.