Program I. Interactions of Emerging Viruses with Host Cell Pathways
Shepherds: Robert Doms, Judith White
Interactions of Emerging Bunyaviruses with Host Cells
The Family Bunyaviridae consists of over 300 viruses with members of four Bunyaviridae genera (Hantavirus, Orthobunyavirus, Phlebovirus and Nairovirus) infecting humans. A number of the Hantaviruses and Rift Valley Fever virus (RVFV, a Phlebovirus) are Category A agents with RVFV being of particular concern.
Identification of Cellular Pathways involved in Rift Valley Fever Virus Infection
The emergence of epidemic arboviral diseases infecting both humans and domestic animals has led to significant world-wide morbidity and mortality. Little is known about the host factors required for the replication cycles of these viruses, and less about the innate immune pathways that restrict pathogenesis, impeding the development of antiviral treatments.
Characterization & Disruption of host protein interactions required for budding of Hendra and Nipah Viruses
Enveloped viruses are formed by a budding process that often requires participation of host proteins. Retroviruses, rhabdoviruses, and filoviruses all use similar late domain sequences within the viral proteins to recruit host factors for budding. Although paramyxoviruses generally lack the same late domain sequences used by these viruses, we have obtained evidence that paramyxoviruses, similar to other enveloped viruses, likely recruit host factors for budding. The viral protein:host protein binding interfaces used during virus budding have the potential to be effective as targets for antiviral drug design.
Inhibition of DNA Modifying Enzymes of Category A-C agents
For applications in biodefense, it is desirable for small molecule inhibitors to target multiple category A-C agents, because it is difficult and expensive to develop even one small molecule inhibitor. Relatively few clinically useful drugs are active against multiple different pathogens. Of the few that are, a substantial fraction target DNA modifying enzymes.