The roles of the ESCRT machinery proteins and Rab35 in human respiratory syncytial virus (HRSV) assembly

• Grant number: 19/22233-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2020
• End date: February 28, 2021
• Field of knowledge: Biological Sciences - Microbiology
• Principal Investigator: Eurico de Arruda Neto
• Grantee: Brenda Cristina Vitti
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Human Respiratory Syncytial Virus (HRSV) belongs to the family Pneumoviridae, genus Orthopneumovirus, and is one of the most important viral pathogens in children worldwide. Despite its public health importance, many aspects regarding the replicative cycle of HRSV remain unclear, as well as its interactions with host proteins that participate in viral assembly and budding. Furthermore, little is known about the exit of HRSV viral proteins by extracellular vesicles. The present study aims to explore that, and has the potential to identify targets of possible HRSV therapy. HRSV replication occurs in the cytoplasm of host cells where the glycoproteins follow the secretory pathway to reach the plasma membrane, where the final steps of assembly and budding take place. It is well accepted that HRSV budding is not dependent on ESCRT and Vps4, which are elements required for other viral replicative cycles. However, a recent study showed that HRSV proteins, as well as its genome, could be released in extracellular vesicles by a process that rely on exosome machinery, opening the possibility that HRSV interacts with ESCRT machinery. Preliminary results of the present research project showed co-localization between HRSV capsid protein N and CHMP4b, an important component of the ESCRT machinery, in addition to co-locazation with Rab35, an import protein for endosomal trafficking and exosome release. Therefore, the project aims to investigate the possible role of CHMP4b and Rab35 proteins in assembly, budding, and exosomal release of HRSV. (AU)