Advances in Immunology and Microbiology Seminar Series: Michael Letko
About the event
Featuring research in the areas of:
Epidemiology | Infectious Disease | Disease Ecology | Drug Discovery | Virology |
Global Health | Vector-Borne Disease | Pathology
The Advances in Immunology & Microbiology seminar series is a weekly forum that brings together scientists from diverse fields and disciplines across the College of Veterinary Medicine to discuss research advances in the broad areas of immunology, microbiology, infectious diseases, and global health. Seminars feature student speakers from the Immunology & Infectious Disease (IID) doctoral program, IID-affiliated postdoctoral researchers and faculty, intramural speakers from across the university, and extramural speakers.
Department of Veterinary Microbiology and Pathology
PRESENTER: Dr. Michael Letko, Assistant Professor, Paul G. Allen School for Global Health
TITLE: Looking for pre-pandemic viral threats with functional viromics
ABSTRACT: The merbecovirus subgenus of coronaviruses includes Middle East Respiratory Syndrome Coronavirus (MERS-CoV), a zoonotic pathogen transmitted from dromedary camels to humans that causes severe respiratory disease. Viral discovery efforts have uncovered hundreds of merbecoviruses in different species across multiple continents, but few have been studied under laboratory conditions, leaving basic questions regarding their human threat potential unresolved. Viral entry into host cells is a critical step for transmission between hosts. As part of our lab’s long-term effort to annotate the virome with tropism data, we developed a scalable approach to assess novel merbecovirus cell entry and evaluated receptor use across the entire merbecovirus subgenus. Merbecoviruses are sorted into clades based on the receptor-binding domain of the spike glycoprotein. Receptor tropism is clade-specific, with the clade including MERS-CoV using DPP4 and multiple clades using ACE2. We identified a receptor for the entire HKU5 complex of bat coronaviruses, which has eluded the field for nearly 20 years since the first HKU5 virus was sequenced. Mutational analysis identified possible structural limitations to HKU5 receptor adaptability and a cryo-EM structure of the HKU5-20s spike trimer revealed only ‘down’ RBDs. These findings re-shape our understanding of merbecovirus cell entry and also provide a foundation for studies developing broadly protective coronavirus vaccines.