2018 New Initiative Grant
Seema Lakdawala, Ph.D. (PI) Assistant Professor of Microbiology and Molecular Genetics, University of Pittsburgh
Nara Lee, Ph.D. (co-investigator) Assistant Professor of Microbiology and Molecular Genetics, University of Pittsburgh
Exploring and Exploiting Influenza Viral Genomic Architecture
Pandemic influenza viruses, like the 2009 ‘swine flu’, emerge through a process known as reassortment, where the genetic material from two different viral strains exchange in a co-infected cell. Reassortment increases virus diversity in nature and is responsible for emergence of all pandemic influenza viruses in the last century. Influenza viruses contain a segmented genome and packaging of one copy of each segment is needed to produce an infectious virus. The segmented nature of the genome makes reassortment possible, but these events do not occur randomly. Importantly, prediction of emerging pandemic influenza viruses has remained elusive since the precise molecular mechanism controlling reassortment is poorly understood. To fully understand the process of reassortment we must first understand intracellular viral genome assembly. In this proposal, we build upon our previous work that revamped the classical view of influenza viral genomic architecture. Specifically, this project is designed to 1) characterize the dynamic nature of the genomic architecture during different stages of infection;; and 2) investigate how viral segments interact with each other during virus assembly. The proposed work will address many outstanding questions related to genome assembly that have remained unanswered because of a lack of cutting-ˇedge tools applied to influenza virology. In addition, these studies may identify regions of the viral genome that can be pursued as potential therapeutic targets.