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. The identification of cellular factors involved in viral replication and pathogenesis has been difficult due to the lack of virus-host systems amenable to genetic screening. Our primary research goal is to use a high-throughput RNAi and small molecule screens in Drosophila and mammalian cells to identify inhibitors of both cellular and viral factors that regulate pathogenesis, including both those factors hijacked by the virus for replication, and those systems used by the host to combat the viral invader. Our studies will be focused on Rift Valley Fever Virus (RVFV, a Category A bunyavirus), but will be extended via collaborations within MARGE to other bunyaviruses of medical significance. RVFV is of particular interest due to its unmet medical and agricultural need, its identification by the USDA as a likely agroterrorism agent, the availability of reagents and experimental systems, and because of the opportunity to collaborate with members of the MARCE. Our cell-based screening approach using replication competent virus enables the identification of compounds or genes that target any factor?viral or cellular?that is required for viral replication. Furthermore, our method has the ability to elucidate the mechanism of this requirement by dissecting viral replication with secondary assays against each step in the lifecycle. The simultaneous application of genome-scale RNAi screens against RVFV and small molecule screens, both using a 384 well plate-based high throughput screening assay (HTS) that we have developed, should lead to more rapid identification of cellular targets for antiviral drug development for this medically important virus, as well as for other members of this under-studied virus family.
Due to the dearth of antiviral therapeutics, there is an urgent need for the discovery of novel small molecules and targets that will lead to therapeutics. This project focuses on the use of novel cell-based screening technology to identify host factors and drugs that impact the replication and pathogenesis Rift Valley Fever virus, an important emerging Category A pathogen, both in the human and insect host.
|Champion, Anna E; Bandara, Aloka B; Mohapatra, Nrusingh et al. (2018) Further Characterization of the Capsule-Like Complex (CLC) Produced by Francisella tularensis Subspecies tularensis: Protective Efficacy and Similarity to Outer Membrane Vesicles. Front Cell Infect Microbiol 8:182|
|Bridge, Dacie R; Blum, Faith C; Jang, Sungil et al. (2017) Creation and Initial Characterization of Isogenic Helicobacter pylori CagA EPIYA Variants Reveals Differential Activation of Host Cell Signaling Pathways. Sci Rep 7:11057|
|Kaempfer, Raymond; Popugailo, Andrey; Levy, Revital et al. (2017) Bacterial superantigen toxins induce a lethal cytokine storm by enhancing B7-2/CD28 costimulatory receptor engagement, a critical immune checkpoint. Receptors Clin Investig 4:|
|Molleston, Jerome M; Cherry, Sara (2017) Attacked from All Sides: RNA Decay in Antiviral Defense. Viruses 9:|
|Cifuentes-Muñoz, Nicolás; Sun, Weina; Ray, Greeshma et al. (2017) Mutations in the Transmembrane Domain and Cytoplasmic Tail of Hendra Virus Fusion Protein Disrupt Virus-Like-Particle Assembly. J Virol 91:|
|Sarute, Nicolás; Ross, Susan R (2017) New World Arenavirus Biology. Annu Rev Virol 4:141-158|
|Ramachandran, Girish; Aheto, Komi; Shirtliff, Mark E et al. (2016) Poor biofilm-forming ability and long-term survival of invasive Salmonella Typhimurium ST313. Pathog Dis 74:|
|Wahid, Rezwanul; Fresnay, Stephanie; Levine, Myron M et al. (2016) Cross-reactive multifunctional CD4+ T cell responses against Salmonella enterica serovars Typhi, Paratyphi A and Paratyphi B in humans following immunization with live oral typhoid vaccine Ty21a. Clin Immunol 173:87-95|
|Li, Huiguang; Hwang, Young; Perry, Kay et al. (2016) Structure and Metal Binding Properties of a Poxvirus Resolvase. J Biol Chem 291:11094-104|
|Chou, Yi-Ying; Cuevas, Christian; Carocci, Margot et al. (2016) Identification and Characterization of a Novel Broad-Spectrum Virus Entry Inhibitor. J Virol 90:4494-4510|
Showing the most recent 10 out of 375 publications