Paul S. Masters
Coronaviruses are a family of enveloped, positive-sense RNA viruses that infect numerous mammalian and avian species and have gained recent widespread attention due to the emergence of severe acute respiratory syndrome (SARS). Our laboratory studies the molecular biology of these viruses using a system we developed that allows the site-specific mutagenesis of the prototype coronavirus mouse hepatitis virus (MHV). Mutations are engineered into the MHV genome via RNA-RNA recombination with synthetic RNA that is introduced into infected cells.
Virion assembly of coronaviruses is the culmination of a series of interactions among a minimal set of four structural proteins and the viral genome at an intracellular budding compartment. Three of the structural proteins are membrane-bound and become incorporated into the virion envelope: the spike protein, which initiates infection through attachment to host cell receptors and fusion with host membranes; the membrane protein, the major constituent of the envelope; and the small envelope protein. In the interior of the virion, the fourth component, the nucleocapsid protein, forms a helical nucleocapsid with the RNA genome. We are particularly interested in determining the roles these proteins play in viral replication and assembly and how they interact with cellular proteins and cause disease in the host.
Our studies are also leading to interesting new insights into the complex mechanism of RNA replication and transcription in coronaviruses. Like all RNA viruses, MHV encodes enzymatic machinery required to make RNA copies of RNA templates, an ability that host cells lack. It is hoped that learning the basic rules of RNA-dependent RNA synthesis will enable the design of inhibitors of this unique viral activity.