Ciara Hu
Postdoctoral Trainee
Department of Microbiology and Immunology
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About
Advisor: Susan Ross
Co-Mentor: Dolly Mehta
Title: The role of SIRPA during influenza infection
Abstract:
Signal regulatory protein alpha (SIRPα) is a transmembrane receptor canonically known to bind to the “don’t eat me” signal, CD47, and inhibit phagocytosis through a signaling cascade. Prior work in our lab demonstrated that SIRPα can also be activated by certain viruses, including H5N1 influenza A virus (IAV), and restrict viral entry. In my first aim, I am investigating how IAV activates SIRPα. I will delineate what part of IAV and IAV-like particles are important for SIRPα activation, whether it is viral proteins or host-derived proteins/sugars/lipids incorporated into the viral envelope. Given that multiple viral families are capable of activating SIRPα, I am also investigating whether viral attachment to the cell triggers integrin-mediated activation of FYN kinase, which then phosphorylates SIRPα. In aim two, I will assess how SIRPα impacts in vivo IAV infections by determining its effects on viral titers and immune responses, as well as its potential role in the differing cell tropism of H1N1 versus H5N1. In all, this project will elucidate the mechanisms underlying SIRPα’s antiviral activity and reveal how SIRPα influences influenza pathogenicity and disease severity.