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

ABSTRACT

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. Using high‐resolution quantitative spatial Comb‐CODEX‐RNAscope, our results confirm 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.