Influenza A virus is a collective name for a large group of different viruses with variable pathogenic potential for humans; (1) non- or low pathogenic influenza A viruses that infect predominantly avian species, (2) moderately pathogenic viruses that can infect humans and other mammals and finally (3) highly pathogenic influenza A viruses, often referred to as “Bird Flu”, with a case fatality rate of 60%. The mechanism and molecular determinants of virulence and pathogenesis are poorly understood and one of the main questions in the laboratory. We will apply reverse genetics technology to generate novel influenza viruses carrying one or more genes of the more pathogenic strains of influenza. In vitro and in vivo testing of these novel viruses will enable us to identify the molecular markers and mechanisms associated with more severe pathology.
We are also very interested in influenza pathogenesis from the perspective of the host. How does immune status and genetic polymorphisms in essential host genes affect pathology after infection? Finally, we will utilize genetically modified mice to study specific gene function in the context of an influenza virus infection. Viral titers, production of inflammatory mediators and the cellular immune response will be quantified after intranasal infection allowing us to dissect the function of the host protein during an infection.
Gene reassortment is a unique evolutionary tool available to segmented viruses, including influenza, allowing efficient transfer of genetic material across different strains of the virus. Reassortment has generated many of the past pandemic influenza viruses. Despite its importance, little is known about the mechanism of reassortment, the bottlenecks for the generation of a novel virus and the genetic requirements enabling the mixing of influenza virus genomes. The Boon lab is using cutting edge sequencing technologies such as CLIP-seq, SHAPE-seq, and SPLASH, to identify RNA structures and interactions in influenza virus and other segmented viruses.
The incidence of emerging virus infection has greatly increased over the last 30 years. Many of these viruses are RNA viruses that jump from an animal reservoir to humans. Examples are Ebola virus, Zika virus, Chikungunya virus, Bourbon virus, Heartland virus, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In order to understand the disease caused by these novel viruses and develop countermeasures such as vaccines, antibodies and antiviral therapies, the Boon lab is developing novel animal models for these diseases in order to prepare for future infections and outbreaks of these viruses.