B-cell Follicles in the Secondary Lymphatic Tissues Act as a Critical Microanatomical Niche for Sustained Viral Replication, Virus-host Interaction and Damage During Chronic SIV Infection of Rhesus Macaques

Most people living with HIV-1 (HIV) are diagnosed during the chronic stage of infection, at which point viral setpoint has been established and a substantial immunopathologic damage in the secondary lymphatic tissues (LTs) has been induced. To better characterize virus-host interaction and immunopathologic damage in LTs, we investigated viral spatial distribution patterns and the corresponding LT structural alterations in SIV chronically infected rhesus macaques. Using RNAscope in-situ hybridization (RNAscope) and a combination of CODEX with RNAscope (Comb-CODEX-RNAscope), we demonstrated that in chronic infection, SIV viral RNA (vRNA) is predominantly resides within B-cell follicles with minimal presence in T-cell zones, and there is significant B-cell follicular damage, encompassing follicular hyperplasia, fibrosis, and disintegration of the germinal center. Our results reveal that the B-cell follicles act as a critical microanatomical niche for sustained viral replication, virus-host interaction and tissue damage during SIV chronic infection.