Mirko Cortese

Biography Research Interests Research Group Publications

Assistant Investigator

Other positions:

Associate Professor of Microbiology, Department of Environmental, Biological and Pharmaceutical Sciences and Technologies,University Luigi Vanvitelli, Caserta, Italy

Mirko Cortese studied Biotechnology at the University of Naples “Federico II”. After his graduation in 2008, he moved to GSK Vaccines (ex Novartis Vaccines and Diagnostics) in Siena for a post-graduate internship in the field of vaccine development. There he pursues his doctorate studies in collaboration with the University of Bologna on the implementation of “reverse vaccinology” to identify novel candidate antigens to develop a vaccine against human Cytomegalovirus. After his PhD in 2013, he moved to Germany for a post-doc in the Department of Infectious Diseases at the University of Heidelberg. There he studied the mechanisms of replication of positive-sense single-stranded RNA (+ssRNA) viruses and how viral infections rewire the host cell to create an environment conducive to viral replication and spread. He investigated two clinically important human pathogens, dengue virus and Zika virus, that can cause severe diseases. He described the ultrastructure of the viral replication organelle, a specialized intracellular compartment formed during +ssRNA virus infection in which viral genome replication takes place. More recently, he characterized the morphological alterations induced during the SARS-CoV-2 replication cycle and described how viral replication affect cellular organelles morphology and function thus contributing to viral cytopathogenicity.

My research interests are focused on how positive-sense single-strand RNA (+ssRNA) viruses, such as SARS-CoV-2, co-opt cellular machineries and remodel cellular organelles to create and environment conducive to viral replication. SARS-CoV-2 replicates its genome in the cytosol in close association with the cellular endomembrane system. Viral proteins, together with host factors, remodel ER membranes to drive the formation of the viral replication organelles (ROs), a virus-induced specialized compartment in which viral genome replication takes place. Due to their central role in viral replication, ROs are attractive candidates for antiviral therapy. Our integrated imaging approach identified a large spectrum of physio-pathological changes associated with SARS-CoV-2 infection, revealing extensive fragmentation of the Golgi apparatus, alteration of the mitochondria morphology, recruitment of peroxisomes to the ROs, and reorganization of the cytoskeleton. However, the functional relevance of such alterations and the molecular mechanisms governing their induction are still largely unknown. In our laboratory, we will combine molecular virology, cell biology and advanced imaging approaches to understand the molecular mechanisms driving ROs biogenesis and virus-induced membrane remodeling.

The final objective of the research project is to identify the key molecular constituents and mechanisms that regulate SARS-CoV-2-induced cytopathogenicity, host-cell alterations and response to infection, with the overall goal of finding ways to limit virus infection and/or reduce the severity of the virus-associated disease.

As SARS-CoV-2 continues to spread, virus variants that diverge from the early isolates are increasingly being identified. Using physiologically relevant cell culture models, we will evaluate the impact of SARS-CoV-2 evolution on cellular pathogenesis and humoral immune evasion and correlate these results to virus transmissibility, clinical pathology, and disease severity.