“This new research promises to identify novel genes and genetic functions that promote virus pathogenesis in the host, leading to new targets for antiviral development and vaccine design,” Baric said. “Our group will focus on genes that contribute to highly pathogenic coronavirus infections, using SARS-CoV and MERS-CoV as a model.”
Other team leaders on the grant include Blossom Damania, PhD, professor of microbiology and immunology at UNC, whose research will focus on the human herpesviruses, and Yoshihiro Kawaoka, PhD, DVM, professor of virology at the University of Wisconsin, who will study Ebola and the highly pathogenic influenza virus gene that regulate disease severity following infection.
Damania’s team will characterize new genes of Kaposi’s sarcoma-associated herpesvirus, an oncogenic DNA virus associated with three different cancers in the human population.
“We will identify novel viral genes that manipulate virus replication efficiency and host responses and may also be associated with the initiation or progression of cancer,” Damania said. “These studies will help us identify novel therapeutic targets to treat viral cancers.”
Using highly pathogenic human respiratory and systemic viruses which cause acute and chronic life-threatening disease outcomes, the researchers will determine whether RNA and DNA viruses encode genetic functions that interface with host genetic components to promote efficient virus replication and regulate host antiviral defense pathways in the cell, resulting in more serious disease outcomes.
By identifying key host genes that are targeted by virus pathogens, the researchers aim to identify therapeutic targets for improving disease outcome by using the body’s mechanisms to slow or stop the disease process.
“We will test the idea that different highly pathogenic viruses have evolved similar functions to regulate several key host antiviral defense pathways, such as inflammation, cell innate immunity, cell cycle regulation and cell death,” Baric said. “If our hypothesis is correct, we will identify common targets for controlling a large number of unrelated viruses, leading to improved public health.”
The approach has several advantages. It is portable and can be applied rapidly to other highly pathogenic respiratory and microbial pathogens; it will rapidly identify novel targets for therapeutic intervention and improve strategies for vaccine design; and it will improve global responses to newly identified epidemic disease outbreaks in human populations.