T‐cell heterogeneity, progenitor–progeny relationships, and function during latent and chronic viral infections

Abstract

SummaryUpon resolution of an acute viral infection, during latent‐reactivating infection and during chronic active infections virus‐specific T‐cells differentiate into distinct subsets that differ in phenotype, longevity, transcriptional, metabolic, and epigenetic profiles, and effector functions. With recent advances in single‐cell profiling, this substantial heterogeneity has become apparent and new subsets of virus‐specific T cells, either of stable or transitory nature, are being identified. A unifying principle of T cells emerging in these different conditions is their precursor–progeny relationship. For acute and resolved viral infections, this relationship becomes apparent during re‐challenge, whereas a constant differentiation of progenitor T cells into more differentiated cells occurs during latent‐reactivating and active chronic viral infections. In this review, we summarize and discuss current knowledge about T‐cell heterogeneity and progenitor–progeny relationships in the setting of persistent viral infections.