As a group, viruses have played major roles in both the number and significance of newly recognized diseases in both animals and humans. A recent example is Australian Bat Lyssavirus (ABLV). ABLV is a newly recognized rabies virus-related rhabdovirus belonging to the genus Lyssavirus and is an enveloped, single-stranded negative-sense RNA virus with an envelope G glycoprotein that is responsible for attachment, membrane fusion, and infection of host cells. ABLV is categorized in Group I of the NIAID Emerging and Re-emerging Diseases list, one circulating in flying foxes (fruit bats) and another in insectivorous bats. Each caused fatal rabies-like encephalitis in humans but with quite different incubation periods. Previously, we developed successful research programs on the henipaviruses (Hendra and Nipah) in our first support period, and many of the tools and expertise derived from those studies along with our collaborative ties with investigators in Australia now offers us the unique opportunity to initiate a new project within the MARCE-2 renewal. Here, we will address several areas related to ABLV binding, entry and infection of host cells, providing new data on this under-researched emerging virus as well as potentially uncovering new information that may be applicable to other viruses within the Mononegavirales, including the filoviruses (Ebola and Marburg) and the henipaviruses (Hendra and Nipah) - areas in which we are well experienced. We have long standing collaborations with leading investigators in Australia: Dr. Linfa Wang at the CSIRO and Dr. Ina Smith at the Public Health Virology unit of Queensland Health, Forensic and Scientific Services. The overall goal of our project is to understand the binding and infection process of ABLV and to identify viral and host cell targets for developing therapeutic intervention strategies. Specifically, we propose to: 1. Explore and characterize the host cell type and species tropisms of ABLV. 2. Develop and characterize soluble monomeric and trimeric forms of ABLV-G;and isolate and characterize human anti-G Fabs and domain antibody (dAb) using phage-display platforms. 3. We will conduct high-throughput RNAi screening for host cell factors required for ABLV infection and growth in cell culture.

Public Health Relevance

Virtually nothing is known about the cell biology and host cell tropism of ABLV and our project will provide new data on this under-studied emerging agent. Through a detailed study of the viral and cellular factors involved in ABLV entry, common therapeutic targets might be discovered that may also be applicable to other related viruses within the Mononegavirales including rabies virus.

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
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