High-Affinity-Mediated Viral Entry Triggers Innate Affinity Escape Resulting in Type I IFN Resistance and Impaired T Cell Immunity

J Immunol. 2024 May 1;212(9):1457-1466. doi: 10.4049/jimmunol.2300637.

Abstract

Increased receptor binding affinity may allow viruses to escape from Ab-mediated inhibition. However, how high-affinity receptor binding affects innate immune escape and T cell function is poorly understood. In this study, we used the lymphocytic choriomeningitis virus (LCMV) murine infection model system to create a mutated LCMV exhibiting higher affinity for the entry receptor α-dystroglycan (LCMV-GPH155Y). We show that high-affinity receptor binding results in increased viral entry, which is associated with type I IFN (IFN-I) resistance, whereas initial innate immune activation was not impaired during high-affinity virus infection in mice. Consequently, IFN-I resistance led to defective antiviral T cell immunity, reduced type II IFN, and prolonged viral replication in this murine model system. Taken together, we show that high-affinity receptor binding of viruses can trigger innate affinity escape including resistance to IFN-I resulting in prolonged viral replication.

MeSH terms

  • Animals
  • Immunity, Innate
  • Lymphocytic Choriomeningitis*
  • Lymphocytic choriomeningitis virus / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Virus Internalization*
  • Virus Replication