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. RVFV, which is spread by infected mosquitoes, was first described in Kenya in 1931 and has since been documented throughout much of Africa and the Arabian peninsula. RVFV causes acute fevers and, sometimes, retinal or hepatic complications with hemorrhagic symptoms. A recent outbreak in Kenya had a case-fatality rate of greater than 20% for those with severe illness. In addition, RVFV causes catastrophic abortion rates in domesticated animals, and thus can causes significant economic losses. As a result, it is categorized as an overlap select agent by both the CDC and the US Department of Agriculture. Also of concern are a number of Hantaviruses that cause hantavirus pulmonary syndrome (HPS) and/or hemorrhagic fever with renal syndrome (HFRS) in humans. Included among these rodent-borne viruses are Sin Nombre virus, Andes virus, and Puumala virus. RVFV and hantaviruses are under-studied pathogens for which there are no approved vaccines or therapeutics. With support from the MARCE beginning in 2005, we launched an effort to study RVFV and, more recently, several hantaviruses. Working with colleagues at USAMRIID, the CDC and at Penn, we have developed a series of genetic tools and functional assays that are being used in high throughput, whole genome RNAi and chemical library screens to identify host cell molecules and pathways needed for the replication and dissemination of these viruses. Significant progress with RVFV has already been made. By studying several bunyaviruses, we hope to identify cellular pathways that are common to this virus family, as well as to identify cellular molecules that are uniquely important to specific viral agents. The overall goal of our project is to identify host cell targets for therapeutic intervention. Specifically, we propose to: 1. Complete our whole genome RNAi and chemical library screens with RVFV, validate hits and determine mechanism of action. 2. Develop the genetic tools, assays and reagents needed to perform whole genome RNAi and chemical library screens for Sin Nombre virus. 3. Determine breadth of action by testing against Andes and Puumala.

Public Health Relevance

All of the viruses being studied in this project are human pathogens. More specifically, they are all viewed as emerging infectious diseases, and all of them are understudied. The CRISP database indicates that are, depending on the virus, either no or very few NIH-funded grants directed towards the study of these viral agents.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Specialized Center--Cooperative Agreements (U54)
Project #
Application #
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Maryland Baltimore
United States
Zip Code
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:
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
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:
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
Ramachandran, Girish; Tennant, Sharon M; Boyd, Mary A et al. (2016) Functional Activity of Antibodies Directed towards Flagellin Proteins of Non-Typhoidal Salmonella. PLoS One 11:e0151875
Molleston, Jerome M; Sabin, Leah R; Moy, Ryan H et al. (2016) A conserved virus-induced cytoplasmic TRAMP-like complex recruits the exosome to target viral RNA for degradation. Genes Dev 30:1658-70
Riblett, Amber M; Blomen, Vincent A; Jae, Lucas T et al. (2016) A Haploid Genetic Screen Identifies Heparan Sulfate Proteoglycans Supporting Rift Valley Fever Virus Infection. J Virol 90:1414-23
Chou, Yi-ying; Cuevas, Christian; Carocci, Margot et al. (2016) Identification and Characterization of a Novel Broad-Spectrum Virus Entry Inhibitor. J Virol 90:4494-510

Showing the most recent 10 out of 373 publications