Human Genetic Defects Resulting in Increased Susceptibility to Viral Infections

Abstract

Protection against viral infections requires a complex series of mechanisms, including integrity of epithelial and mucosal barriers, cell-intrinsic mechanisms of recognition of viral nucleic acids, and both innate and adaptive immune responses. In particular, T and natural killer (NK) cells play a critical role in antiviral immune responses by killing virus-infected cells. Moreover, recognition of viral nucleic acids by Toll-like receptors and RIG-I/MDA5 induce type I and type III interferon (IFN) responses in virus-infected cells, promoting expression of IFN-dependent genes, which encode proteins that restrain viral replication and infectivity. This article reviews a large number of inborn errors of immunity that result in increased susceptibility to viral infections, either in the context of a broader susceptibility to infections or as selective predisposition to viral infections.