Inborn errors of autophagy and infectious diseases

Abstract

Autophagy is a fundamental component of cell-autonomous immunity, targeting intracellular pathogens including viruses and cytosolic bacteria to lysosomes for degradation. Genetic mutations in components of the autophagy pathway result in autoinflammatory and neurodegenerative disorders. We focus on recent developments through the newly discovered inborn errors of autophagy strictly predisposing to severe viral infections. These feature mutations in TBK1, ATG4A, MAP1LC3B2, and ATG7, leading to herpes encephalitis, recurrent lymphocytic meningitis, and paralytic poliomyelitis. We highlight how this enhances our understanding of autophagy mechanisms and its role in human viral disease. As we better understand the contribution of these genes to disease, we can aim to develop targeted therapies for enhanced infection control.