Understanding viral-host interactions at the organismal, cellular, and molecular levels are vital in mitigating viral pathogenesis. The goals of this project are to discover the viral microbiome and the role of innate immunity in the regulation of viral symbioses in the model organism Hydra. By doing so, it will be determined whether Hydra contain viruses similar to human viruses as well as testing Hydra-specific genes responsive to viral presence. Hydra provide an ideal model to test these host-pathogen interactions because of their simplistic composition, their ease of experimental manipulation, and their epithelial exposure to the environment without a protective barrier. Further, Hydra lack adaptive immunity features, do not contain motile phagocytic cells, and only utilize mucus as a means to preserve its epithelium. Therefore, Hydra are uniquely suited for the study of host-pathogen interactions at the mucosal epithelium. To establish this, the project consists of two specific aims: 1.) Identify Hydra viral communities utilizing viral metagenomics. The purpose of this aim is to discover the viruses associating with Hydra, whether they are induced under stress, and to deduce whether these viruses are involved in human pathogenesis. 2.) Elucidate the Hydra antiviral response in the presence of cytosolic nucleic acids. Specific Hydra antiviral innate immune response genes possess greater similarities to humans than that of flies and worms. Therefore, monitoring Hydra innate immune genes in response to viral presence will clarify the effects made by viruses at the epithelium. By accomplishing these two aims, viruses that cause pathogenic conditions in Hydra will be identified as well as viruses that similarly cause human pathogenesis harbored within Hydra. Once identified, cultivatable viruses can then be tested in this Hydra innate immunity model system. If the etiologic agent cannot be cultured, the identified agent genes will be used to test Hydra antiviral recognition. Further, by identifying the Hydra antiviral genes responsive to viral infection, Hydra will be manipulated through gene knockdown, to determine which genes are vital in either limiting viral pathogenesis or promoting viral symbiosis.

Public Health Relevance

Viruses are the most abundant entities on Earth and all cellular organisms have mechanisms built to recognize them. However, not all viruses cause Human pathogenesis. The purpose of this project is to develop Hydra as a model organism to study host interactions with pathogenic or symbiotic viruses.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32AI098418-02
Application #
8519046
Study Section
Special Emphasis Panel (ZRG1-F13-C (20))
Program Officer
Park, Eun-Chung
Project Start
2012-11-01
Project End
2015-10-31
Budget Start
2013-11-01
Budget End
2014-10-31
Support Year
2
Fiscal Year
2014
Total Cost
$58,370
Indirect Cost
Name
San Diego State University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
073371346
City
San Diego
State
CA
Country
United States
Zip Code
92182
Grasis, Juris A; Lachnit, Tim; Anton-Erxleben, Friederike et al. (2014) Species-specific viromes in the ancestral holobiont Hydra. PLoS One 9:e109952
Quistad, Steven D; Stotland, Aleksandr; Barott, Katie L et al. (2014) Evolution of TNF-induced apoptosis reveals 550 My of functional conservation. Proc Natl Acad Sci U S A 111:9567-72
Bosch, Thomas C G; Adamska, Maja; Augustin, René et al. (2014) How do environmental factors influence life cycles and development? An experimental framework for early-diverging metazoans. Bioessays 36:1185-94