BBB webinar: Carolyn E. Machamer

Carolyn E. Machamer
Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

SARS CoV-2, the virus that causes COVID-19, is a member of the family of coronaviruses that cause respiratory and gastrointestinal disease in vertebrates. Coronaviruses are enveloped RNA viruses that assemble by budding into the endoplasmic reticulum (ER)-Golgi intermediate compartment. After budding, virus particles must make their way out of the infected cell, a process that is not well understood. Our work has focused on virus assembly and egress from infected cells. The three envelope proteins (S, M and E) are targeted to the assembly compartment after synthesis in the ER. They interact with each other and with the N protein-wrapped RNA genome to form virions that bud into the lumen of the ER-Golgi intermediate compartment. Virus particles (120 nm) are much larger than most endogenous cargoes in the secretory pathway, and virion release is less efficient than in case of enveloped viruses that bud from the plasma membrane. How do coronaviruses traverse the cell for secretion? For the model coronavirus infectious bronchitis virus (IBV), the small E protein neutralizes the pH of the Golgi lumen. Although this slows host membrane traffic, it prevents aberrant cleavage of the S protein, which is essential for infection. Interestingly, SARS CoV-1 also neutralizes Golgi pH, but uses a different protein (ORF3a) and a different mechanism. Thus, neutralization of acidic compartments may be a universal feature of CoV infection and suggests a novel target for antiviral therapeutics.

Chairperson: Jaakko Saraste, Department of Biomedicine