Prof. Mirko Cortese - Telethon Institute of Genetics and Medicine (TIGEM)
Abstract
AN ORGANELLE-RESOLVED TRANSLOCOME ATLAS OF CORONAVIRUS-INFECTED CELLS REVEALS CONSERVED HOST DEPENDENCY AND RESTRICTION FACTORS AMONG +RNA VIRUSES
Upon infection, positive-sense single-stranded RNA (+RNA) viruses remodel the host endomembrane system to establish a favorable environment for viral replication. The most striking among the alterations induced by the infection of +RNA viruses is the formation of the viral replication organelle (RO), a specialized membrane-delimited organelle where the viral genome replication takes place. For SARS-CoV-2, the etiological agent of the COVID-19 disease, the viral ROs are composed of double membrane vesicles that originate from and are in contact with the endoplasmic reticulum. The reorganization of the cellular architecture may contribute to the cytopathic effects observed during infection. However, the host and viral factors, as well as the molecular mechanisms underlying RO biogenesis and virus-induced cellular remodeling, remain poorly understood. To shed light on such factors, we performed organelle organelle-resolved proteomics in Coronavirus-infected cells to define the cellular “translocome,” encompassing host proteins that relocalize in response to infection. Genetic pertubation screening performed on a selected list of translocating proteins revealed previously unrecognized host dependency and restriction factors for SARS-CoV-2. Notably, several of these factors are conserved across different RNA viruses, suggesting the existence of a shared evolutionary strategy for host manipulation and replication organelle formation.
BIO
Mirko Cortese completed his PhD in 2013 at the GSK vaccines in collaboration with the University of Bologna studying novel antigens for vaccine development against human Cytomegalovirus. He then moved to the Center for Integrative Infectious Disease Research at the Heidelberg University in group of Ralf Bartenschlager. There he studied the replication mechanisms of positive-sense single-stranded RNA viruses, such as dengue and Zika virus. In 2021 he got an independent group leader position at the Telethon Institute of Genetics and Medicine in Pozzuoli, Italy. He received the Early Career Fellowship from the Human Technopole to establish a research program on the cytopathogenic processes induced by SARS-CoV-2 replication. In 2022 he became associate professor in microbiology at the University Luigi Vanvitelli in Caserta. His current research focuses on host-pathogen interactions in the context of viruses with pandemic potential.
