Work

Defining the proteolytic landscape during enterovirus infection

Year: 2020

Type: article

Abstract: Viruses cleave cellular proteins to remodel the host proteome.The study of these cleavages has revealed mechanisms of immune evasion, resource exploitation, and pathogenesis.However, the full extent of virus-induced proteolysis in infected cells is unknown, mainly because until recently the technology for a global view of proteolysis within cells was lacking.Here, we report the first comprehensive catalog of proteins cleaved upon enterovirus infection and identify the sites within proteins where the cleavages occur.We employed multiple strategies to confirm protein cleavages and assigned them to one of the two enteroviral proteases.Detailed characterization of one substrate, LSM14A, a p body protein with a role in antiviral immunity, showed that cleavage of this protein disrupts its antiviral function.This study yields a new depth of information about the host interface with a group of viruses that are both important biological tools and significant agents of disease. Author summaryEnteroviruses are associated with a variety of human diseases, including gastroenteritis, the common cold, hand-foot-and-mouth disease, acute hemorrhagic conjunctivitis, and skin rash.In some cases, the infection can lead to myocarditis, encephalitis, progressive muscle weakness, and paralysis.Exactly how enteroviruses invade human tissues, defeat the host immune system, and alter normal cell biology is unknown.Understanding these cellular and molecular mechanisms will blaze the trail for the development of novel vaccine and therapeutic strategies.Here, we have applied a global N-terminomics approach

Source: PLoS Pathogens

DOI: 10.1371/journal.ppat.1008927