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-DDS-M)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Maryland Baltimore
United States
Zip Code
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
Ray, Greeshma; Schmitt, Phuong Tieu; Schmitt, Anthony P (2016) C-Terminal DxD-Containing Sequences within Paramyxovirus Nucleocapsid Proteins Determine Matrix Protein Compatibility and Can Direct Foreign Proteins into Budding Particles. J Virol 90:3650-60
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
Fraley, Stephanie I; Athamanolap, Pornpat; Masek, Billie J et al. (2016) Nested Machine Learning Facilitates Increased Sequence Content for Large-Scale Automated High Resolution Melt Genotyping. Sci Rep 6:19218
Levy, Revital; Rotfogel, Ziv; Hillman, Dalia et al. (2016) Superantigens hyperinduce inflammatory cytokines by enhancing the B7-2/CD28 costimulatory receptor interaction. Proc Natl Acad Sci U S A 113:E6437-E6446
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
Ramachandran, Girish; Boyd, Mary Adetinuke; MacSwords, Jennifer et al. (2016) Opsonophagocytic Assay To Evaluate Immunogenicity of Nontyphoidal Salmonella Vaccines. Clin Vaccine Immunol 23:520-3
Plaut, Roger D; Stibitz, Scott (2015) Improvements to a Markerless Allelic Exchange System for Bacillus anthracis. PLoS One 10:e0142758

Showing the most recent 10 out of 360 publications