Caenorhabditis elegans as an Emerging Model for Virus-Host Interactions

Abstract

Since 1999, Caenorhabditis elegans has been extensively used to study microbe-host interactions due to its simple culture, genetic tractability, and susceptibility to numerous bacterial and fungal pathogens. In contrast, virus studies have been hampered by a lack of convenient virus infection models in nematodes. The recent discovery of a natural viral pathogen of C. elegans and development of diverse artificial infection models are providing new opportunities to explore virushost interplay in this powerful model organism.KEYWORDS Caenorhabditis elegans, Flock House virus, innate immunity, Orsay virus, RNA interference, virus-host interactions, vesicular stomatitis virus I n the past 40 years, the free-living nematode Caenorhabditis elegans has been used in diverse fields such as neurobiology, RNA interference (RNAi), and pathogen-host interactions. As a model, C. elegans offers many advantages, including genetic tractability, small size, and inexpensive culture. Its sexually dimorphic nature and short reproductive cycle make genetic crosses and rearing large numbers of animals simple. As C. elegans naturally feeds on bacteria (1), one can often initiate intestinal infection by using the microbe of interest as a food source. Furthermore, the transparent body of C. elegans permits visualization of fluorescently tagged pathogens and tissue pathologies. Well-defined techniques for genetically modifying the laboratory strain (N2) make identifying nematode factors influencing pathogen susceptibilities relatively straightforward (2, 3). RNAi is also easily performed by feeding nematodes bacteria expressing double-stranded RNAs (dsRNAs) targeting the gene of interest. This "feeding" RNAi response spreads to most tissues and can be inherited, allowing inhibition of gene expression in adults and progeny.Although lacking the classic adaptive immunity found in vertebrates that relies on specialized immune cells, C. elegans employs a variety of innate and nonclassic adaptive immune responses that are shared with other metazoans (i.e., antiviral RNAi) (4, 5). An estimated 38% of the ϳ20,250 protein-encoding genes in C. elegans have human orthologs (6), and several antimicrobial pathways found in mammals are also found in worms (4,5,(7)(8)(9). Therefore, C. elegans can be used to explore conserved immunological mechanisms.Since the establishment of a Pseudomonas aeruginosa infection model in 1999 (10, 11), dozens of bacterial and fungal pathogens (including several that infect humans) have been shown to cause disease in C. elegans (reviewed in [1,9]). Studies of these predominantly extracellular pathogens have largely shaped our understanding of C. elegans immunity. However, with the recent discovery of natural intracellular pathogens of C. elegans (12, 13) and the development of nonnatural virus infection models (14-18), this is beginning to change.Here virus-C. elegans interaction models (Table 1) are discussed in terms of their features, advantages/disadvantages, and contributions to our understanding of C. elegan...

Genetic Variation in Caenorhabditis elegans Responses to Pathogenic Microbiota

“…Caenorhabditis elegans (Nematoda; Rhabditidae) is a cosmopolitan hermaphroditic nematode that thrives on bacteria in rotting plant material [1,2]. It was introduced as a tractable species for biological research during the early 1970s [3], and since then, it has been established as a widely used model species in biological research. As a bacterivorous nematode, C. elegans populations can easily be reared in the lab.…”

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“…From its initial establishment as a model until earlier this decade, there were no known viruses that could naturally infect C. elegans . Therefore, the first studies of virus–host interactions in C. elegans relied upon surrogate systems that included analysis of C. elegans cells, artificial infection conditions, or replicons [ 78 , 79 ]. Specifically, these entailed studies of vesicular stomatitis virus (VSV) infection of primary C. elegans cell culture [ 34 , 35 ], artificial virus infection in C. elegans using vaccinia virus [ 37 ], and a flock house virus transgenic system [ 38 ] ( Table 1 ).…”

Caenorhabditis elegans, a Host to Investigate the Probiotic Properties of Beneficial Microorganisms

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