Skip to main content
Top
Published in: Archives of Virology 11/2014

01-11-2014 | Brief Review

The nematode Caenorhabditis elegans as a model to study viruses

Authors: Jesica Diogo, Ana Bratanich

Published in: Archives of Virology | Issue 11/2014

Login to get access

Abstract

Caenorhabditis elegans is a worm that has been extensively studied, and it is today an accepted model in many different biological fields. C. elegans is cheap to maintain, it is transparent, allowing easy localization studies, and it develops from egg to adult in around 4 days. Many mutants, available to the scientific community, have been developed. This has facilitated the study of the role of particular genes in many cellular pathways, which are highly conserved when compared with higher eukaryotes. This review describes the advantages of C. elegans as a laboratory model and the known mechanisms utilized by this worm to fight pathogens. In particular, we describe the strong C. elegans RNAi machinery, which plays an important role in the antiviral response. This has been shown in vitro (C. elegans cell cultures) as well as in vivo (RNAi-deficient strains) utilizing recently described viruses that have the worm as a host. Infections with mammalian viruses have also been achieved using chemical treatment. The role of viral genes involved in pathogenesis has been addressed by evaluating the phenotypes of transgenic strains of C. elegans expressing those genes. Very simple approaches such as feeding the worm with bacteria transformed with viral genes have also been utilized. The advantages and limitations of different approaches are discussed.
Literature
1.
go back to reference Culetto E, Sattelle DB (2000) A role for Caenorhabditis elegans in understanding the function and interactions of human disease genes. Hum Mol Genet 9:869–877PubMedCrossRef Culetto E, Sattelle DB (2000) A role for Caenorhabditis elegans in understanding the function and interactions of human disease genes. Hum Mol Genet 9:869–877PubMedCrossRef
3.
go back to reference Hunt-Newbury R, Viveiros R, Johnsen R, Mah A, Anastas D et al (2007) High-throughput in vivo analysis of gene expression in Caenorhabditis elegans. PLoS Biol 5:e237PubMedCrossRefPubMedCentral Hunt-Newbury R, Viveiros R, Johnsen R, Mah A, Anastas D et al (2007) High-throughput in vivo analysis of gene expression in Caenorhabditis elegans. PLoS Biol 5:e237PubMedCrossRefPubMedCentral
5.
go back to reference Chalfie M, Tu Y, Euskirchen G, Ward WW, Prasher DC (1994) Green fluorescent protein as a marker for gene expression. Science 263:802–805PubMedCrossRef Chalfie M, Tu Y, Euskirchen G, Ward WW, Prasher DC (1994) Green fluorescent protein as a marker for gene expression. Science 263:802–805PubMedCrossRef
6.
go back to reference Riddle DL, Blumenthal T, Meyer BJ, Priess JR (1997) Introduction to C. elegans. In: Riddle DL, Blumenthal T, Meyer BJ, Priess JR (eds) C. elegans II, 2nd edn. Cold Sprinh Harbor Laboratory Press, Cold Spring Harbor, NY, pp 1–23 Riddle DL, Blumenthal T, Meyer BJ, Priess JR (1997) Introduction to C. elegans. In: Riddle DL, Blumenthal T, Meyer BJ, Priess JR (eds) C. elegans II, 2nd edn. Cold Sprinh Harbor Laboratory Press, Cold Spring Harbor, NY, pp 1–23
7.
go back to reference Kurz CL, Ewbank JJ (2003) Caenorhabditis elegans: an emerging genetic model for the study of innate immunity. Nat Rev Genet 4:380–390PubMedCrossRef Kurz CL, Ewbank JJ (2003) Caenorhabditis elegans: an emerging genetic model for the study of innate immunity. Nat Rev Genet 4:380–390PubMedCrossRef
8.
go back to reference Tan MW, Ausubel FM (2000) Caenorhabditis elegans: a model genetic host to study Pseudomonas aeruginosa pathogenesis. Curr Opin Microbiol 3:29–34PubMedCrossRef Tan MW, Ausubel FM (2000) Caenorhabditis elegans: a model genetic host to study Pseudomonas aeruginosa pathogenesis. Curr Opin Microbiol 3:29–34PubMedCrossRef
10.
go back to reference Zhuang JJ, Hunter CP (2012) RNA interference in Caenorhabditis elegans: uptake, mechanism, and regulation. Parasitology 139:560–573PubMedCrossRef Zhuang JJ, Hunter CP (2012) RNA interference in Caenorhabditis elegans: uptake, mechanism, and regulation. Parasitology 139:560–573PubMedCrossRef
11.
go back to reference Grishok A, Tabara H, Mello CC (2000) Genetic requirements for inheritance of RNAi in C. elegans. Science 287:2494–2497PubMedCrossRef Grishok A, Tabara H, Mello CC (2000) Genetic requirements for inheritance of RNAi in C. elegans. Science 287:2494–2497PubMedCrossRef
12.
go back to reference Sijen T, Fleenor J, Simmer F, Thijssen KL, Parrish S et al (2001) On the role of RNA amplification in dsRNA-triggered gene silencing. Cell 107:465–476PubMedCrossRef Sijen T, Fleenor J, Simmer F, Thijssen KL, Parrish S et al (2001) On the role of RNA amplification in dsRNA-triggered gene silencing. Cell 107:465–476PubMedCrossRef
13.
go back to reference Evans DG, Birch JM, Ramsden RT, Sharif S, Baser ME (2006) Malignant transformation and new primary tumours after therapeutic radiation for benign disease: substantial risks in certain tumour prone syndromes. J Med Genet 43:289–294PubMedCrossRefPubMedCentral Evans DG, Birch JM, Ramsden RT, Sharif S, Baser ME (2006) Malignant transformation and new primary tumours after therapeutic radiation for benign disease: substantial risks in certain tumour prone syndromes. J Med Genet 43:289–294PubMedCrossRefPubMedCentral
15.
go back to reference Irazoqui JE, Urbach JM, Ausubel FM (2010) Evolution of host innate defence: insights from Caenorhabditis elegans and primitive invertebrates. Nat Rev Immunol 10:47–58PubMedCrossRefPubMedCentral Irazoqui JE, Urbach JM, Ausubel FM (2010) Evolution of host innate defence: insights from Caenorhabditis elegans and primitive invertebrates. Nat Rev Immunol 10:47–58PubMedCrossRefPubMedCentral
17.
go back to reference Pujol N, Link EM, Liu LX, Kurz CL, Alloing G et al (2001) A reverse genetic analysis of components of the toll signaling pathway in Caenorhabditis elegans. Curr Biol 11:809–821PubMedCrossRef Pujol N, Link EM, Liu LX, Kurz CL, Alloing G et al (2001) A reverse genetic analysis of components of the toll signaling pathway in Caenorhabditis elegans. Curr Biol 11:809–821PubMedCrossRef
18.
go back to reference Pradel E, Zhang Y, Pujol N, Matsuyama T, Bargmann CI et al (2007) Detection and avoidance of a natural product from the pathogenic bacterium Serratia marcescens by Caenorhabditis elegans. Proc Natl Acad Sci USA 104:2295–2300PubMedCrossRefPubMedCentral Pradel E, Zhang Y, Pujol N, Matsuyama T, Bargmann CI et al (2007) Detection and avoidance of a natural product from the pathogenic bacterium Serratia marcescens by Caenorhabditis elegans. Proc Natl Acad Sci USA 104:2295–2300PubMedCrossRefPubMedCentral
20.
go back to reference Gravato-Nobre MJ, Stroud D, O’Rourke D, Darby C, Hodgkin J (2011) Glycosylation genes expressed in seam cells determine complex surface properties and bacterial adhesion to the cuticle of Caenorhabditis elegans. Genetics 187:141–155PubMedCrossRefPubMedCentral Gravato-Nobre MJ, Stroud D, O’Rourke D, Darby C, Hodgkin J (2011) Glycosylation genes expressed in seam cells determine complex surface properties and bacterial adhesion to the cuticle of Caenorhabditis elegans. Genetics 187:141–155PubMedCrossRefPubMedCentral
22.
go back to reference Partridge FA, Gravato-Nobre MJ, Hodgkin J (2010) Signal transduction pathways that function in both development and innate immunity. Dev Dyn 239:1330–1336PubMed Partridge FA, Gravato-Nobre MJ, Hodgkin J (2010) Signal transduction pathways that function in both development and innate immunity. Dev Dyn 239:1330–1336PubMed
23.
go back to reference Hamilton AJ, Baulcombe DC (1999) A species of small antisense RNA in posttranscriptional gene silencing in plants. Science 286:950–952PubMedCrossRef Hamilton AJ, Baulcombe DC (1999) A species of small antisense RNA in posttranscriptional gene silencing in plants. Science 286:950–952PubMedCrossRef
24.
go back to reference Li H, Li WX, Ding SW (2002) Induction and suppression of RNA silencing by an animal virus. Science 296:1319–1321PubMedCrossRef Li H, Li WX, Ding SW (2002) Induction and suppression of RNA silencing by an animal virus. Science 296:1319–1321PubMedCrossRef
25.
go back to reference Knight SW, Bass BL (2001) A role for the RNase III enzyme DCR-1 in RNA interference and germ line development in Caenorhabditis elegans. Science 293:2269–2271PubMedCrossRefPubMedCentral Knight SW, Bass BL (2001) A role for the RNase III enzyme DCR-1 in RNA interference and germ line development in Caenorhabditis elegans. Science 293:2269–2271PubMedCrossRefPubMedCentral
26.
go back to reference Lu R, Yigit E, Li WX, Ding SW (2009) An RIG-I-Like RNA helicase mediates antiviral RNAi downstream of viral siRNA biogenesis in Caenorhabditis elegans. PLoS Pathog 5:e1000286PubMedCrossRefPubMedCentral Lu R, Yigit E, Li WX, Ding SW (2009) An RIG-I-Like RNA helicase mediates antiviral RNAi downstream of viral siRNA biogenesis in Caenorhabditis elegans. PLoS Pathog 5:e1000286PubMedCrossRefPubMedCentral
27.
go back to reference Sarkies P, Miska EA (2013) RNAi pathways in the recognition of foreign RNA: antiviral responses and host-parasite interactions in nematodes. Biochem Soc Trans 41:876–880PubMedCrossRef Sarkies P, Miska EA (2013) RNAi pathways in the recognition of foreign RNA: antiviral responses and host-parasite interactions in nematodes. Biochem Soc Trans 41:876–880PubMedCrossRef
28.
go back to reference Tomari Y, Zamore PD (2005) MicroRNA biogenesis: drosha can’t cut it without a partner. Curr Biol 15:R61–R64PubMedCrossRef Tomari Y, Zamore PD (2005) MicroRNA biogenesis: drosha can’t cut it without a partner. Curr Biol 15:R61–R64PubMedCrossRef
29.
go back to reference Ashe A, Belicard T, Le Pen J, Sarkies P, Frezal L et al (2013) A deletion polymorphism in the Caenorhabditis elegans RIG-I homolog disables viral RNA dicing and antiviral immunity. Elife 2:e00994PubMedCrossRefPubMedCentral Ashe A, Belicard T, Le Pen J, Sarkies P, Frezal L et al (2013) A deletion polymorphism in the Caenorhabditis elegans RIG-I homolog disables viral RNA dicing and antiviral immunity. Elife 2:e00994PubMedCrossRefPubMedCentral
30.
go back to reference Smardon A, Spoerke JM, Stacey SC, Klein ME, Mackin N et al (2000) EGO-1 is related to RNA-directed RNA polymerase and functions in germ-line development and RNA interference in C. elegans. Curr Biol 10:169–178PubMedCrossRef Smardon A, Spoerke JM, Stacey SC, Klein ME, Mackin N et al (2000) EGO-1 is related to RNA-directed RNA polymerase and functions in germ-line development and RNA interference in C. elegans. Curr Biol 10:169–178PubMedCrossRef
31.
go back to reference Ketting RF, Fischer SE, Bernstein E, Sijen T, Hannon GJ et al (2001) Dicer functions in RNA interference and in synthesis of small RNA involved in developmental timing in C. elegans. Genes Dev 15:2654–2659PubMedCrossRefPubMedCentral Ketting RF, Fischer SE, Bernstein E, Sijen T, Hannon GJ et al (2001) Dicer functions in RNA interference and in synthesis of small RNA involved in developmental timing in C. elegans. Genes Dev 15:2654–2659PubMedCrossRefPubMedCentral
32.
go back to reference Parrish S, Fire A (2001) Distinct roles for RDE-1 and RDE-4 during RNA interference in Caenorhabditis elegans. RNA 7:1397–1402PubMedPubMedCentral Parrish S, Fire A (2001) Distinct roles for RDE-1 and RDE-4 during RNA interference in Caenorhabditis elegans. RNA 7:1397–1402PubMedPubMedCentral
33.
go back to reference Tabara H, Sarkissian M, Kelly WG, Fleenor J, Grishok A et al (1999) The rde-1 gene, RNA interference, and transposon silencing in C. elegans. Cell 99:123–132PubMedCrossRef Tabara H, Sarkissian M, Kelly WG, Fleenor J, Grishok A et al (1999) The rde-1 gene, RNA interference, and transposon silencing in C. elegans. Cell 99:123–132PubMedCrossRef
34.
go back to reference Felix MA, Ashe A, Piffaretti J, Wu G, Nuez I et al (2011) Natural and experimental infection of Caenorhabditis nematodes by novel viruses related to nodaviruses. PLoS Biol 9:e1000586PubMedCrossRefPubMedCentral Felix MA, Ashe A, Piffaretti J, Wu G, Nuez I et al (2011) Natural and experimental infection of Caenorhabditis nematodes by novel viruses related to nodaviruses. PLoS Biol 9:e1000586PubMedCrossRefPubMedCentral
35.
go back to reference Galiana-Arnoux D, Dostert C, Schneemann A, Hoffmann JA, Imler JL (2006) Essential function in vivo for Dicer-2 in host defense against RNA viruses in drosophila. Nat Immunol 7:590–597PubMedCrossRef Galiana-Arnoux D, Dostert C, Schneemann A, Hoffmann JA, Imler JL (2006) Essential function in vivo for Dicer-2 in host defense against RNA viruses in drosophila. Nat Immunol 7:590–597PubMedCrossRef
37.
go back to reference Schott DH, Cureton DK, Whelan SP, Hunter CP (2005) An antiviral role for the RNA interference machinery in Caenorhabditis elegans. Proc Natl Acad Sci USA 102:18420–18424PubMedCrossRefPubMedCentral Schott DH, Cureton DK, Whelan SP, Hunter CP (2005) An antiviral role for the RNA interference machinery in Caenorhabditis elegans. Proc Natl Acad Sci USA 102:18420–18424PubMedCrossRefPubMedCentral
38.
go back to reference Lu R, Maduro M, Li F, Li HW, Broitman-Maduro G et al (2005) Animal virus replication and RNAi-mediated antiviral silencing in Caenorhabditis elegans. Nature 436:1040–1043PubMedCrossRefPubMedCentral Lu R, Maduro M, Li F, Li HW, Broitman-Maduro G et al (2005) Animal virus replication and RNAi-mediated antiviral silencing in Caenorhabditis elegans. Nature 436:1040–1043PubMedCrossRefPubMedCentral
40.
go back to reference Li WX, Li H, Lu R, Li F, Dus M et al (2004) Interferon antagonist proteins of influenza and vaccinia viruses are suppressors of RNA silencing. Proc Natl Acad Sci USA 101:1350–1355PubMedCrossRefPubMedCentral Li WX, Li H, Lu R, Li F, Dus M et al (2004) Interferon antagonist proteins of influenza and vaccinia viruses are suppressors of RNA silencing. Proc Natl Acad Sci USA 101:1350–1355PubMedCrossRefPubMedCentral
42.
go back to reference Hengartner MO, Ellis RE, Horvitz HR (1992) Caenorhabditis elegans gene ced-9 protects cells from programmed cell death. Nature 356:494–499PubMedCrossRef Hengartner MO, Ellis RE, Horvitz HR (1992) Caenorhabditis elegans gene ced-9 protects cells from programmed cell death. Nature 356:494–499PubMedCrossRef
43.
go back to reference Zou H, Henzel WJ, Liu X, Lutschg A, Wang X (1997) Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3. Cell 90:405–413PubMedCrossRef Zou H, Henzel WJ, Liu X, Lutschg A, Wang X (1997) Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3. Cell 90:405–413PubMedCrossRef
44.
go back to reference Yuan J, Shaham S, Ledoux S, Ellis HM, Horvitz HR (1993) The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1 beta-converting enzyme. Cell 75:641–652PubMedCrossRef Yuan J, Shaham S, Ledoux S, Ellis HM, Horvitz HR (1993) The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1 beta-converting enzyme. Cell 75:641–652PubMedCrossRef
45.
go back to reference Conradt B, Horvitz HR (1998) The C. elegans protein EGL-1 is required for programmed cell death and interacts with the Bcl-2-like protein CED-9. Cell 93:519–529PubMedCrossRef Conradt B, Horvitz HR (1998) The C. elegans protein EGL-1 is required for programmed cell death and interacts with the Bcl-2-like protein CED-9. Cell 93:519–529PubMedCrossRef
46.
go back to reference Liu WH, Lin YL, Wang JP, Liou W, Hou RF et al (2006) Restriction of vaccinia virus replication by a ced-3 and ced-4-dependent pathway in Caenorhabditis elegans. Proc Natl Acad Sci USA 103:4174–4179PubMedCrossRefPubMedCentral Liu WH, Lin YL, Wang JP, Liou W, Hou RF et al (2006) Restriction of vaccinia virus replication by a ced-3 and ced-4-dependent pathway in Caenorhabditis elegans. Proc Natl Acad Sci USA 103:4174–4179PubMedCrossRefPubMedCentral
47.
go back to reference Franz CJ, Zhao G, Felix MA, Wang D (2012) Complete genome sequence of Le Blanc virus, a third Caenorhabditis nematode-infecting virus. J Virol 86:11940PubMedCrossRefPubMedCentral Franz CJ, Zhao G, Felix MA, Wang D (2012) Complete genome sequence of Le Blanc virus, a third Caenorhabditis nematode-infecting virus. J Virol 86:11940PubMedCrossRefPubMedCentral
48.
go back to reference Sarkies P, Ashe A, Le Pen J, McKie MA, Miska EA (2013) Competition between virus-derived and endogenous small RNAs regulates gene expression in Caenorhabditis elegans. Genome Res 23:1258–1270PubMedCrossRefPubMedCentral Sarkies P, Ashe A, Le Pen J, McKie MA, Miska EA (2013) Competition between virus-derived and endogenous small RNAs regulates gene expression in Caenorhabditis elegans. Genome Res 23:1258–1270PubMedCrossRefPubMedCentral
49.
go back to reference Sugimoto A, Friesen PD, Rothman JH (1994) Baculovirus p35 prevents developmentally programmed cell death and rescues a ced-9 mutant in the nematode Caenorhabditis elegans. EMBO J 13:2023–2028PubMedPubMedCentral Sugimoto A, Friesen PD, Rothman JH (1994) Baculovirus p35 prevents developmentally programmed cell death and rescues a ced-9 mutant in the nematode Caenorhabditis elegans. EMBO J 13:2023–2028PubMedPubMedCentral
50.
go back to reference Lee LW, Chang TY, Lo HW, Lo SJ (2011) Hepatitis D antigens cause growth retardation and brood-size reduction in C. elegans. Front Biosci (Elite Ed) 3:380–390CrossRef Lee LW, Chang TY, Lo HW, Lo SJ (2011) Hepatitis D antigens cause growth retardation and brood-size reduction in C. elegans. Front Biosci (Elite Ed) 3:380–390CrossRef
51.
go back to reference Geng X, Harry BL, Zhou Q, Skeen-Gaar RR, Ge X et al (2012) Hepatitis B virus X protein targets the Bcl-2 protein CED-9 to induce intracellular Ca2+ increase and cell death in Caenorhabditis elegans. Proc Natl Acad Sci USA 109:18465–18470PubMedCrossRefPubMedCentral Geng X, Harry BL, Zhou Q, Skeen-Gaar RR, Ge X et al (2012) Hepatitis B virus X protein targets the Bcl-2 protein CED-9 to induce intracellular Ca2+ increase and cell death in Caenorhabditis elegans. Proc Natl Acad Sci USA 109:18465–18470PubMedCrossRefPubMedCentral
52.
go back to reference Nazir A, Sammi SR, Singh P, Tripathi RK (2010) Trans-cellular introduction of HIV-1 protein Nef induces pathogenic response in Caenorhabditis elegans. PLoS One 5:e15312PubMedCrossRefPubMedCentral Nazir A, Sammi SR, Singh P, Tripathi RK (2010) Trans-cellular introduction of HIV-1 protein Nef induces pathogenic response in Caenorhabditis elegans. PLoS One 5:e15312PubMedCrossRefPubMedCentral
53.
go back to reference Choffnes ER, Olsen L, Wizemann TM (2013) Institute of Medicine (U.S.) Forum on microbial threats the science and applications of microbial genomics: workshop summary. xxiv, p 403 Choffnes ER, Olsen L, Wizemann TM (2013) Institute of Medicine (U.S.) Forum on microbial threats the science and applications of microbial genomics: workshop summary. xxiv, p 403
54.
go back to reference Franz CJ, Renshaw H, Frezal L, Jiang Y, Felix MA et al (2014) Orsay, Santeuil and Le Blanc viruses primarily infect intestinal cells in Caenorhabditis nematodes. Virology 448:255–264PubMedCrossRef Franz CJ, Renshaw H, Frezal L, Jiang Y, Felix MA et al (2014) Orsay, Santeuil and Le Blanc viruses primarily infect intestinal cells in Caenorhabditis nematodes. Virology 448:255–264PubMedCrossRef
Metadata
Title
The nematode Caenorhabditis elegans as a model to study viruses
Authors
Jesica Diogo
Ana Bratanich
Publication date
01-11-2014
Publisher
Springer Vienna
Published in
Archives of Virology / Issue 11/2014
Print ISSN: 0304-8608
Electronic ISSN: 1432-8798
DOI
https://doi.org/10.1007/s00705-014-2168-2

Other articles of this Issue 11/2014

Archives of Virology 11/2014 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine