Unique Gene Expression Profile in Youth with Human Immunodeficiency Virus (HIV) Suppression on ART: Implications for Novel Diagnostic or Therapeutic Targets

Authors

• JA Rich
• SI Coates-Park
• S Gurung
• Y Liu
• A Govil
• S Kaur
• D Roberts
• W Stetler-Stevenson
• D Peeney

Abstract

Background. Antiretroviral therapy (ART) suppresses HIV replication, but viral infection persists. We analyzed gene expression in youth with HIV (YWH) on ART with or without sustained viral suppression and youth without HIV (YWOH) to reveal molecular bioprofiles associated with control or persistence of viral replication.

Methods. Peripheral blood cell mRNA was profiled using Affymetrix HG-U133 Plus 2.0 Arrays for 52 participants (27 YWH and 25 YWOH) balanced for age, gender, and race. Among 27 YWH (18-23 years), 19 achieved sustained viral suppression (VS) (< 50 RNA copies/ml plasma), while 8 had detectable viral replication (VNS). Differentially expressed genes (DEGs) were identified using samr package (FC ≥ 1.3 and FDR ≤ 0.05). Pathway analyses were based on the Gene Ontology database, while Protein-Protein Interaction networks were inferred from the STRING database.

Results. Compared to YWOH, VNS YWH showed 1003 DEGs with 47 perturbed pathways related to interferon signaling and defense against viruses, while VS YWH had 14 perturbed pathways with 367 DEGs, including platelet activation and regulation of serine/threonine protein kinase. Unique hub genes regulating chronic inflammation (HSP90AB1, RhoA, PDGFA, and STK4) were observed in youth with VS compared to YWOH. Direct comparison between VS or VNS YWH identified 131 DEGs involved in DNA repair, RNA processing, and negative regulation of RNA polymerase II transcription pathways, while YY1, Dicer1, and XRCC2 were hub genes associated with viral suppression in youth.

Conclusions. Youth on ART with viral suppression display distinct molecular profiles that could guide personalized treatment and diagnostics for HIV resurgence.

Scientific Focus Area: Virology

This page was last updated on Monday, September 25, 2023