Study of the interactions between SARS-CoV2 and the host cell endomembrane system.

• Grant number: 23/02880-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Effective date (Start): June 01, 2023
• Effective date (End): May 31, 2025
• Field of knowledge: Biological Sciences - Microbiology
• Principal Investigator: Luis Lamberti Pinto da Silva
• Grantee: Jared Rudd
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 19/26119-0 - Emerging and re-emerging viruses: biology, pathogenesis and prospection, AP.TEM

Abstract

The interactions between viral factors and the host cell endomembrane system are of fundamental importance for the replication and pathogenesis of SARS-CoV-2. The assembly and externalization of CoVs involve: 1) the invagination of the limiting membrane of the ER-Golgi intermediate compartment (ERGIC) with the consequent budding of nascent viral particles into its interior and 2) the fusion of the modified ERGIC with the plasmatic membrane. Usually, the structural protein M is responsible for nucleating the other structural proteins (E, S, and N) in the membrane of these organelles. However, the conservation of these processes for SARS-CoV-2 is unknown, and the host cell factors that mediate these events are elusive for CoVs in general. In this project, we intend to identify the determinants of targeting and localization of the structural glycoproteins of SARS-CoV-2 (E and M) through assays with VLPs (virus-like particles) in human cell lines. In addition, we will perform a targeted screening of intracellular traffic regulatory proteins to identify elements of this machinery subverted by the virus during the replicative cycle.