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

Journal of immunology (Baltimore, Md. : 1950)

Authors: Haifeng C Xu, Piyush Pandey, Harry Ward, Michal Gorzkiewicz, Džiuljeta Abromavičiūtė, Constanze Tinz, Lisa Müller, Caroline Meyer, Aleksandra A Pandyra, Aslihan Yavas, Arndt Borkhardt, Irene Esposito, Karl S Lang, Philipp A Lang

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.

Copyright © 2024 by The American Association of Immunologists, Inc.

PMID: 38497668