HCV Persistence and Immune Evasion in the Absence of Memory T Cell Help

Abstract

Spontaneous resolution of hepatitis C virus (HCV) infection in humans usually affords long-term immunity to persistent viremia and associated liver diseases. Here, we report that memory CD4⁺ Tcells are essential for this protection. Antibody-mediated depletion of CD4⁺ Tcells before reinfection of two immune chimpanzees resulted in persistent, low-level viremia despite functional intra-hepatic memory CD8⁺ Tcell responses. Incomplete control of HCV replication by memory CD8⁺ Tcells in the absence of adequate CD4⁺ Tcell help was associated with emergence of viral escape mutations in class I major histocompatibility complex–restricted epitopes and failure to resolve HCV infection.