Early treatment in pediatric HIV infection restores epigenetic regulation for normal lymph node development 2372

Abstract Description Our previous studies indicate that lymphoid follicles and germinal centers (GCs) develop rapidly within the first few weeks of life, while SIV infection in newborns significantly impairs follicle and GC formation. Our recent findings indicate that early initiation of antiretroviral therapy (ART) in neonatal macaques, beginning 3 days post-SIV infection (dpi) at birth, achieves sustained virologic remission. However, the effects of early ART on lymph node (LN) development and the underlying molecular mechanisms remain unclear. In this study, newborn macaques intravenously inoculated with SIV received combination ART (cART) starting at 3 dpi for a period of 9 months, compared with age-matched uninfected controls. LN biopsies were collected to assess follicle and GC formation and to isolate B cells for transcriptome and chromatin immunoprecipitation (ChIP) sequencing analysis. Results demonstrated that early ART in SIV-exposed infants restored follicular and GC B cell proliferation, follicle and GC formation, and BCR diversity, regulated through epigenetic silencing of cell cycle suppressors at the level of histone methylation. These findings suggest that early HIV prevention interventions in infants exposed to or infected with HIV promote ART-free remission and normal immune development in pediatric populations. Funding Sources This work was supported by National Institutes of Health grants MH133474, HD099857, and P51 OD011104. Topic Categories Viral Immunology (VIR)