Review Article

DOI :10.26650/EurJBiol.2022.1079841   IUP :10.26650/EurJBiol.2022.1079841    Full Text (PDF)

Enigmatic Entities of the Acellular World: Viruses, Viroids, and Virusoids

Sidhant JainSoumen Das

Genetic material confined within the lipid based cellular boundaries was earlier considered synonymous with life. However, with the discovery of viruses in late 19th century, the existence of acellular biological entities was established. Viruses, viroids, and virusoids are unique entities which have different relationships with different life forms ranging from mutualistic to parasitic ones. These entities provide evidence in support of the idea of ‘RNA world’ in the origin of life on Earth. In the present time, viruses are relatively well studied but the same cannot be said for viroids and virusoids. There has been a growing focus on the impact of these entities, in terms of human welfare as well as their impact on susceptible varieties of plants. As a result, studying their origin, evolution and pathogenicity has become a subject of the uttermost importance. In this review, we have discussed different facets of viruses, viroids and virusoids like their historical background, classification and mode of entry and replication in the host. We have also summarized various possible theories on their origin and evolution and have provided our take on it. This work indicates the possibility that different viruses originated distinctly by utilizing different strategies and evolved further. Clues like small size and high GC content in genomes indicate that viroids must be an important component of the pre-cellular world and it is possible that they might have originated before viruses. Furthermore, as viroids and virusoids show certain conserved properties, it suggests a probable link between them.

PDF View


  • 1. ICVCN (2021). The international code of virus classification and nomenclature. ( google scholar
  • 2. Agut H, Fillet AM and Calvez V. Qu’est-ce qu’un virus? [What is a virus?]. La Revue du praticien 1997; 47(6): 602-7. google scholar
  • 3. Diener TO. Potato spindle tuber “virus”. IV. A replicating, low molec-ular weight RNA. Virology 1971; 45(2): 411-28. google scholar
  • 4. Gross HJ, Domdey H, Lossow C, Jank P, Raba M, Alberty H, et al. Nucleotide sequence and secondary structure of potato spindle tuber viroid. Nature 1978; 273(5659): 203-8. google scholar
  • 5. Sanger HL, Klotz G, Riesner D, Gross HJ and Kleinschmidt AK. Vi-roids are single-stranded covalently closed circular RNA molecules existing as highly base-paired rod-like structures. Proc Natl Acad Sci U S A 1976; 73(11): 3852-6. google scholar
  • 6. Hu CC, Hsu YH and Lin NS. Satellite RNAs and Satellite Viruses of Plants. Viruses 2009; 1(3): 1325-50. google scholar
  • 7. Palukaitis P. Satellite RNAs and Satellite Viruses. Mol Plant Microbe Interact 2016; 29(3): 181-6. google scholar
  • 8. Palukaitis P. What has been happening with viroids? Virus Genes 2014; 49(2): 175-84. google scholar
  • 9. AbouHaidar MG, Venkataraman S, Golshani A, Liu B and Ahmad T. Novel coding, translation, and gene expression of a replicating covalently closed circular RNA of 220 nt. Proc Natl Acad Sci U S A 2014; 111(40): 14542-7. google scholar
  • 10. Salvato MS and Fraenkel-Conrat H. Translation of tobacco necrosis virus and its satellite in a cell-free wheat germ system. Proc Natl Acad Sci U S A 1977; 74(6): 2288-92. google scholar
  • 11. Coffin JM, Hughes SH, Varmus HE, editors. Retroviruses. Cold Spring Harbor (NY): Cold Spring Harbor Laboratory Press; 1997. google scholar
  • 12. Temin HM and Baltimore D. RNA-directed DNA synthesis and RNA tumor viruses. Adv Virus Res 1972; 17: 129-86. google scholar
  • 13. Gilbert W. Origin of life: The RNA world. Nature 1986; 319: 618. google scholar
  • 14. Rao AL and Kalantidis K. Virus-associated small satellite RNAs and viroids display similarities in their replication strategies. Virology 2015; 479-480: 627-36. google scholar
  • 15. Koonin EV and Dolja VV. A virocentric perspective on the evolution of life. Curr Opin Virol 2013; 3(5): 546-57. google scholar
  • 16. Iwanowski D. “Über die Mosaikkrankheit der Tabakspflanze”. Bul-letin Scientifique Publie Par l’Academie Imperiale des Sciences de Saint-Petersbourg Nouvelle Serie III 1892; 35: 67-70. google scholar
  • 17. Loeffler F and Frosch P. Berichte der kommission zur erforschung der maulund klauenseuche bei dem institut ftjr infektionskrank-heiten in Berlin. Centb Bakt 1898; 23(1): 371-91. google scholar
  • 18. Twort FW. An investigation on the nature of ultra-microscopic vi-ruses. Lancet 1915; 2: 1241-3. google scholar
  • 19. d’Herelle F. An invisible microbe that is antagonistic to the dysen-tery bacillus. Comptes Rendus Academie Sciences Paris, 1917; 165: 373-5. google scholar
  • 20. Harada LK, Silva EC, Campos WF, Del Fiol FS, Vila M, Dqbrowska K, et al. Biotechnological applications of bacteriophages: State of the art. Microbiol Res 2018; 212-213:38-58. google scholar
  • 21. Principi N, Silvestri E and Esposito S Advantages and Limitations of Bacteriophages for the Treatment of Bacterial Infections. Front Pharmacol 2019; 10: 513. google scholar
  • 22. Jain S and Kumar S. Cancer immunotherapy: dawn of the death of cancer? Int Rev Immunol 2020; 39: 1-18. google scholar
  • 23. Barquinero J, Eixarch H and Perez-Melgosa, M. Retroviral vectors: new applications for an old tool. Gene Ther 2004; 11: 3-9. google scholar
  • 24. Smith W, Andrewes CH and Laidlaw PP. A virus obtained from influ-enza patients. Lancet 1933; 2: 66-8. google scholar
  • 25. Potter CW. A history of influenza. J Appl Microbiol 2001; 91(4): 572-9. google scholar
  • 26. Taubenberger JK and Morens DM. Pandemic influenza--including a risk assessment of H5N1. Rev Sci Tech 2009; 28(1): 187-202. google scholar
  • 27. Yin Y and Wunderink RG. MERS, SARS and other coronaviruses as causes of pneumonia. Respirology 2018; 23(2): 130-7. google scholar
  • 28. Diener TO. Discovering viroids-a personal perspective. Nat Rev Mi-crobiol 2003; 1(1): 75-80. google scholar
  • 29. Davies JW, Kaesberg P and Diener TO. Potato spindle tuber viroid. XII. An investigation of viroid RNA as a messenger for protein syn-thesis. Virology 1974; 61: 281-6. google scholar
  • 30. Owens RA and Hammond RW. Viroid pathogenicity: one process, many faces. Viruses 2009; 1(2): 298-316. google scholar
  • 31. Adkar-Purushothama CR and Perreault J. Current overview on vi-roid-host interactions. Wiley Interdisciplinary Reviews: RNA 2019; 11: e1570. google scholar
  • 32. Randles J, Davies C, Hatta T, Gould A and Francki R. Studies on en-capsidated viroid-like RNA I. Characterization of velvet tobacco mottle virus. Virology 1981; 108(1): 111-22. google scholar
  • 33. Aiewsakun P and Katzourakis A. Time-Dependent Rate Phenome-non in Viruses. J Virol 2016; 90(16): 7184-95. google scholar
  • 34. Koonin EV, Dolja VV and Krupovic M. Origins and evolution of vi-ruses of eukaryotes: The ultimate modularity. Virology 2015; 479480: 2-25. google scholar
  • 35. Louten J. Virus Structure and Classification. Essential Human Virol-ogy 2016; 19-29. google scholar
  • 36. International Committee on Taxonomy of Viruses Executive Com-mittee. The new scope of virus taxonomy: partitioning the viro-sphere into 15 hierarchical ranks. Nature microbiology 2020; 5(5): 668-674. google scholar
  • 37. Elena SF, Dopazo J, Flores R, Diener TO and Moya A. Phylogeny of viroids, viroidlike satellite RNAs, and the viroidlike domain of hep-atitis delta virus RNA. Proc Natl Acad Sci U S A 1991; 88(13): 5631-4. google scholar
  • 38. Flores R, Gago-Zachert S, Serra P, Sanjuan R and Elena SF. Viroids: sur-vivors from the RNA world? Annu Rev Microbiol 2014; 68: 395-414. google scholar
  • 39. Choi H, Jo Y, Cho WK, Yu J, Tran PT, Salaipeth L, et al. Identification of Viruses and Viroids Infecting Tomato and Pepper Plants in Vietnam by Metatranscriptomics. Int J Mol Sci 2020; 21(20): 7565. google scholar
  • 40. Bester R, Cook G, Breytenbach JHJ, Steyn C, De Bruyn R, Maree HJ. Towards the validation of high-throughput sequencing (HTS) for routine plant virus diagnostics: measurement of variation linked to HTS detection of citrus viruses and viroids. Virol J 2021; 18: 61. google scholar
  • 41. Di Serio F, Li SF, Matousek J, Owens RA, Pallas V, Randles JW, et al. ICTV Virus Taxonomy Profile: Avsunviroidae. J Gen Virol 2018; 99(5): 611-2. google scholar
  • 42. Di Serio F, Owens RA, Li SF, Matousek J, Pallas V, Randles JW, et al. ICTV Virus Taxonomy Profile: Pospiviroidae. J Gen Virol 2021; 102(2): 001543. google scholar
  • 43. Tsagris EM, Martinez de Alba AE, Gozmanova M and Kalantidis K. Viroids. Cell Microbiol 2008; 10(11): 2168-79. google scholar
  • 44. ICTV (2011). Satellites and Other Virus-dependent Nucleic Acids, ICTV 9th Report. google scholar
  • 45. Alves C, Branco C and Cunha C. Hepatitis delta virus: a peculiar vi-rus. Adv Virol 2013; 560105. google scholar
  • 46. Durzynska J and Gozdzicka-Jözefiak A. Viruses and cells inter-twined since the dawn of evolution. Virol J 2015; 12: 169. google scholar
  • 47. d’ Herelle F.The bacteriophage: its röle in immunity. Baltimore: Wil-liams & Wilkins. 1922. google scholar
  • 48. Wessner DR. The Origins of Viruses. Nature Education 2010; 3(9):37. google scholar
  • 49. Koonin EV, Senkevich TG and Dolja VV. Compelling reasons why viruses are relevant for the origin of cells. Nat Rev Microbiol 2009; 7(8): 615. google scholar
  • 50. Nasir A, Kim KM and Caetano-Anolles G. Giant viruses coexisted with the cellular ancestors and represent a distinct supergroup along with superkingdoms Archaea, Bacteria and Eukarya. BMC Evol Biol 2012; 12: 156. google scholar
  • 51. Salehi-Ashtiani K, Luptak A, Litovchick A and Szostak JW. A ge-nomewide search for ribozymes reveals an HDV-like sequence in the human CPEB3 gene. Science 2006; 313(5794):1788-92. google scholar
  • 52. La Scola B, Audic S, Robert C, Jungang L, de Lamballerie X, Dran-court M, et al. A giant virus in amoebae. Science 2003; 299(5615): 2033. google scholar
  • 53. Krupovic M and Koonin EV. Multiple origins of viral capsid proteins from cellular ancestors. Proc Natl Acad Sci U S A 2017; 114(12): 2401-10. google scholar
  • 54. Domingo E, Escarmus C, Sevilla N, Moya A, Elena SF, Quer J, et al. Basic concepts in RNA virus evolution. FASEB J 1996; 10(8): 859-64. google scholar
  • 55. Sanjuan R and Domingo-Calap P. Mechanisms of viral mutation. Cell Mol Life Sci 2016; 73(23): 4433-48. google scholar
  • 56. Taubenberger JK and Kash JC. Influenza virus evolution, host ad-aptation, and pandemic formation. Cell Host Microbe 2010; 7(6): 440-51. google scholar
  • 57. Spreeuwenberg P, Kroneman M and Paget J. Reassessing the Global Mortality Burden of the 1918 Influenza Pandemic. Am J Epidemi-ol 2018; 187(12): 2561-67. google scholar
  • 58. Shao W, Li X, Goraya MU, Wang S and Chen JL. Evolution of Influ-enza A Virus by Mutation and Re-Assortment. Int J Mol Sci 2017; 18(8). google scholar
  • 59. Russell RJ, Kerry PS, Stevens DJ, Steinhauer DA, Martin SR, Gam-blin SJ, et al. Structure of influenza hemagglutinin in complex with an inhibitor of membrane fusion. Proc Natl Acad Sci U S A 2008; 105(46): 17736-41. google scholar
  • 60. Tong S, Zhu X, Li Y, Shi M, Zhang J, Bourgeois M, et al. New world bats harbor diverse influenza A viruses. PLoS Pathog 2013; 9(10): e1003657. google scholar
  • 61. Mostafa A, Abdelwhab EM, Mettenleiter TC and Pleschka, S. Zoo-notic Potential of Influenza A Viruses: A Comprehensive Overview. Viruses 2018; 10(9). google scholar
  • 62. Das SR, Hensley SE, Ince WL, Brooke CB, Subba A, Delboy MG, et al. Defining influenza A virus hemagglutinin antigenic drift by se-quential monoclonal antibody selection. Cell Host Microbe 2013; 13(3): 314-23. google scholar
  • 63. Webster RG and Govorkova EA. Continuing challenges in influen-za. Ann N Y Acad Sci 2014; 1323: 115-39. google scholar
  • 64. Taubenberger JK. The origin and virulence of the 1918 “Spanish” influenza virus. Proc Am Philos Soc 2006; 150(1): 86-112. google scholar
  • 65. Urbaniak K and Markowska-Daniel I. In vivo reassortment of influ-enza viruses. Acta Biochim Pol 2014; 61(3): 427-31. google scholar
  • 66. Neumann G, Noda T and Kawaoka Y. Emergence and pandem-ic potential of swine-origin H1N1 influenza virus. Nature 2008; 459(7249): 931-9. google scholar
  • 67. Gracia JCM. Novel insights in the adaptation of avian H9N2 influ-enza viruses to swine. (Doctor of Philosophy (Ph.D.), 2017); Ghent University, Belgium. google scholar
  • 68. Orlich M, Gottwald H and Rott, R. Nonhomologous recombination between the hemagglutinin gene and the nucleoprotein gene of an influenza virus. Virology 1994; 204(1): 462-5. google scholar
  • 69. Dahourou G, Guillot S, Le Gall O, Crainic R. Genetic recombination in wild-type poliovirus. J Gen Virol 2002; 83: 3103-10. google scholar
  • 70. Diener TO. Origin and evolution of viroids and viroid-like satellite RNAs. Virus Genes 1995; 11(2-3): 119-31. google scholar
  • 71. Cervera A and De la Pena, M. Eukaryotic penelope-like retroele-ments encode hammerhead ribozyme motifs. Mol Biol Evol 2014; 31(11): 2941-7. google scholar
  • 72. Cervera A, Urbina D and De la Pena M. Retrozymes are a unique family of non-autonomous retrotransposons with hammerhead ri-bozymes that propagate in plants through circular RNAs. Genome Biol 2016; 17: 135. google scholar
  • 73. Kiefer MC, Owens RA and Diener TO. Structural similarities be-tween viroids and transposable genetic elements. Proc Natl Acad Sci U S A 1983; 80(20): 6234-8. google scholar
  • 74. Diener TO . Circular RNAs: relics of precellular evolution? Proc Natl Acad Sci U S A 1989; 86(23): 9370-4. google scholar
  • 75. Gago S, Elena SF, Flores R and Sanjuan, R. Extremely high muta-tion rate of a hammerhead viroid. Science (New York, N.Y.) 2009; 323(5919): 1308. google scholar
  • 76. Lopez-Carrasco A, Ballesteros C, Sentandreu V, Delgado S, Ga-go-Zachert S, Flores R, et al. Different rates of spontaneous mu-tation of chloroplastic and nuclear viroids as determined by high-fidelity ultra-deep sequencing. PLoS pathogens 2017; 13(9): e1006547. google scholar
  • 77. Wu J and Bisaro DM. Biased Pol II fidelity contributes to conserva-tion of functional domains in the Potato spindle tuber viroid ge-nome. PLoS pathogens 2020; 16(12): e1009144. google scholar
  • 78. Eigen M and Schuster P.The hypercycle. A principle of natural self-organization. Part C: the realistic hypercycle. Naturwissen-schaften 1978; 65: 341-69. google scholar
  • 79. Dinter-Gottlieb G. Viroids and virusoids are related to group I in-trons. Proc Natl Acad Sci U S A 1986; 83(17): 6250-4. google scholar
  • 80. Mothes W, Sherer NM, Jin J and Zhong P. Virus cell-to-cell transmis-sion. J Virol 2010; 84(17): 8360-8. google scholar
  • 81. Thorley JA, McKeating JA and Rappoport JZ. Mechanisms of viral entry: sneaking in the front door. Protoplasma 2010; 244(1-4): 15-24. google scholar
  • 82. Madshus IH, Olsnes S and Sandvig K. Mechanism of entry into the cytosol of poliovirus type 1: requirement for low pH. J Cell Biol 1984; 98(4): 1194-200. google scholar
  • 83. Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. A pneu-monia outbreak associated with a new coronavirus of probable bat origin. Nature 2020; 579 (7798): 270-3. google scholar
  • 84. Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, et al. Angio-tensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 2003; 426(6965): 450-4. google scholar
  • 85. Guo Y, Korteweg C, McNutt MA and Gu J. Pathogenetic mecha-nisms of severe acute respiratory syndrome. Virus Res 2008; 133(1): 4-12. google scholar
  • 86. Plemper R. K. Cell entry of enveloped viruses. Curr Opin Virol 2011; 1(2): 92-100. google scholar
  • 87. Cohen FS. How Viruses Invade Cells. Biophys J 2016; 110(5): 102832. google scholar
  • 88. Sieczkarski SB and Whittaker GR. Differential requirements of Rab5 and Rab7 for endocytosis of influenza and other enveloped virus-es. Traffic (Copenhagen, Denmark) 2003; 4(5): 333-43. google scholar
  • 89. Walsh D and Mohr I. Viral subversion of the host protein synthesis machinery. Nat Rev Microbiol 2011; 9: 860-75. google scholar
  • 90. Rampersad S and Tennant P. Replication and Expression Strategies of Viruses. Viruses 2018; 55-82. google scholar
  • 91. Keen EC and Dantas G. Close Encounters of Three Kinds: Bacterio-phages, Commensal Bacteria, and Host Immunity. Trends Microbi-ol 2018; 26(11): 943-54. google scholar
  • 92. Desfarges S and Ciuffi A. Viral Integration and Consequences on Host Gene Expression. Viruses: Essential Agents of Life 2012; 14775. google scholar
  • 93. Chung BN and Pak HS. Seed transmission of Chrysanthemum stunt viroid in Chrysanthemum. Plant Pathol J 2008; 24(1): 31-5. google scholar
  • 94. Ding B, Zhong X and Flores R. Viroids/Virusoids. Reference Module in Life Sciences 2017. DOI: 10.1016/B978-0-12-809633-8.13120-6. google scholar
  • 95. Daros JA, Elena SF and Flores R. Viroids: an Ariadne’s thread into the RNA labyrinth. EMBO reports 2006; 7(6): 593-8. google scholar
  • 96. Branch AD and Robertson HD. A replication cycle for viroids and other small infectious RNA’s. Science 1984; 223(4635): 450-5. google scholar
  • 97. Flores R,Gas ME, Molina-Serrano D, Nohales MÂ,Carbonell A, Gago S, et al. Viroid replication: rolling-circles, enzymes and ribozymes. Viruses 2009; 1(2): 317-34. google scholar
  • 98. Roossinck MJ, Sleat D and Palukaitis P. Satellite RNAs of plant vi-ruses: structures and biological effects. Microbiol Rev 1992; 56(2): 265-79. google scholar
  • 99. Gellatly D, Mirhadi K, Venkataraman S and AbouHaidar MG. Struc-tural and sequence integrity are essential for the replication of the viroid-like satellite RNA of lucerne transient streak virus. J Gen Virol 2011; 92(Pt 6): 1475-81. google scholar
  • 100. Sheldon CC and Symons RH. Is hammerhead self-cleavage in-volved in the replication of a virusoid in vivo? Virology 1993; 194(2): 463-74. google scholar
  • 101. Matousek J, Steinbachova L, Drabkova LZ, Kocabek T, Potesil D, Mishra AK, et al. Elimination of Viroids from Tobacco Pollen In-volves a Decrease in Propagation Rate and an Increase of the Deg-radation Processes. Int J Mol Sci 2020; 21(8): 3029. google scholar
  • 102. Carbonell A, Martinez de Alba AE, Flores R and Gago S. Dou-ble-stranded RNA interferes in a sequence-specific manner with the infection of representative members of the two viroid families. Virology 2008; 371(1): 44-53. google scholar


Copy and paste a formatted citation or use one of the options to export in your chosen format



Jain, S., & Das, S. (2022). Enigmatic Entities of the Acellular World: Viruses, Viroids, and Virusoids. European Journal of Biology, 81(1), 85-95.


Jain S, Das S. Enigmatic Entities of the Acellular World: Viruses, Viroids, and Virusoids. European Journal of Biology. 2022;81(1):85-95.


Jain, S.; Das, S. Enigmatic Entities of the Acellular World: Viruses, Viroids, and Virusoids. European Journal of Biology, [Publisher Location], v. 81, n. 1, p. 85-95, 2022.

Chicago: Author-Date Style

Jain, Sidhant, and Soumen Das. 2022. “Enigmatic Entities of the Acellular World: Viruses, Viroids, and Virusoids.” European Journal of Biology 81, no. 1: 85-95.

Chicago: Humanities Style

Jain, Sidhant, and Soumen Das. Enigmatic Entities of the Acellular World: Viruses, Viroids, and Virusoids.” European Journal of Biology 81, no. 1 (Dec. 2022): 85-95.

Harvard: Australian Style

Jain, S & Das, S 2022, 'Enigmatic Entities of the Acellular World: Viruses, Viroids, and Virusoids', European Journal of Biology, vol. 81, no. 1, pp. 85-95, viewed 7 Dec. 2022,

Harvard: Author-Date Style

Jain, S. and Das, S. (2022) ‘Enigmatic Entities of the Acellular World: Viruses, Viroids, and Virusoids’, European Journal of Biology, 81(1), pp. 85-95. (7 Dec. 2022).


Jain, Sidhant, and Soumen Das. Enigmatic Entities of the Acellular World: Viruses, Viroids, and Virusoids.” European Journal of Biology, vol. 81, no. 1, 2022, pp. 85-95. [Database Container],


Jain S, Das S. Enigmatic Entities of the Acellular World: Viruses, Viroids, and Virusoids. European Journal of Biology [Internet]. 7 Dec. 2022 [cited 7 Dec. 2022];81(1):85-95. Available from: doi: 10.26650/EurJBiol.2022.1079841


Jain, Sidhant - Das, Soumen. Enigmatic Entities of the Acellular World: Viruses, Viroids, and Virusoids”. European Journal of Biology 81/1 (Dec. 2022): 85-95.


Published Online16.05.2022


Attribution-NonCommercial (CC BY-NC)

This license lets others remix, tweak, and build upon your work non-commercially, and although their new works must also acknowledge you and be non-commercial, they don’t have to license their derivative works on the same terms.


Istanbul University Press aims to contribute to the dissemination of ever growing scientific knowledge through publication of high quality scientific journals and books in accordance with the international publishing standards and ethics. Istanbul University Press follows an open access, non-commercial, scholarly publishing.