View source for Viroid

{{short description|Pathogenic small single-stranded circular RNA}}
{{For|a variant of it which is dependent on viruses|Virusoid}}
{{Cs1 config|name-list-style=vanc}}
{{Virusbox
| image = PSTviroid.png
| taxon = Viroid
| subdivision_ranks = Families
| subdivision = ''[[Pospiviroidae]]''<br>''[[Avsunviroidae]]''
}}

'''Viroids''' are small single-stranded, [[circular RNA]]s that are infectious pathogens.<ref name="Navarro">{{cite journal |last1=Navarro |first1=Beatriz |last2=Flores |first2=Ricardo |last3=Di Serio |first3=Francesco |title=Advances in Viroid-Host Interactions |journal=Annual Review of Virology |date=29 September 2021 |volume=8 |issue=1 |pages=305–325|doi-access=free |doi=10.1146/annurev-virology-091919-092331 |pmid=34255541 |issn=2327-056X}}</ref><ref>{{cite web |last1=Di Serio |first1=Francesco |last2=Owens |first2=Robert A. |last3=Li |first3=Shi-Fang |last4=Matoušek |first4=Jaroslav |last5=Pallás |first5=Vicente |last6=Randles |first6=John W. |last7=Sano |first7=Teruo |last8=Verhoeven |first8=Jacobus Th. J. |last9=Vidalakis |first9=Georgios |last10=Flores |first10=Ricardo |date=November 2020 |editor-last=Zerbini |editor-first=F. Murilo |editor2-last=Sabanadzovic |editor2-first=Sead |title=Viroids |url=https://talk.ictvonline.org/ictv-reports/ictv_online_report/subviral-agents/w/viroids |access-date=February 3, 2021 |url-status=dead |archive-date=December 2, 2020 |archive-url=https://web.archive.org/web/20201202061614/https://talk.ictvonline.org/ictv-reports/ictv_online_report/subviral-agents/w/viroids}}</ref> Unlike [[virus]]es, they have no protein coating. All known viroids are inhabitants of [[angiosperms]] (flowering plants),<ref>{{cite journal |vauthors=Hadidi A |title=Next-Generation Sequencing and CRISPR/Cas13 Editing in Viroid Research and Molecular Diagnostics |journal=Viruses |volume=11 |issue=2 |pages=120 |date=January 2019 |pmid=30699972 |pmc=6409718 |doi=10.3390/v11020120 |doi-access=free}}</ref> and most cause diseases, whose respective [[Agricultural economics|economic]] importance to humans varies widely.<ref name="pmid32752288">{{cite journal |vauthors=Adkar-Purushothama CR, Perreault JP |title=Impact of Nucleic Acid Sequencing on Viroid Biology |journal=International Journal of Molecular Sciences |volume=21 |issue=15 |date=August 2020 |page=5532 |pmid=32752288 |pmc=7432327 |doi=10.3390/ijms21155532 |url=|doi-access=free }}</ref> A recent [[metatranscriptomics]] study suggests that the host diversity of viroids and other viroid-like elements is broader than previously thought and that it would not be limited to plants, encompassing even the [[prokaryotes]].<ref name=Lee>{{cite journal |vauthors=Lee BD, Neri U, Roux S, Wolf YI, Camargo AP, Krupovic M |collaboration=RNA Virus Discovery Consortium; Simmonds P, Kyrpides N, Gophna U, Dolja VV, Koonin EV |title=Mining metatranscriptomes reveals a vast world of viroid-like circular RNAs |journal=Cell |date=2 Feb 2023 |volume=186 |issue=3 |pages=646–661 |doi=10.1016/j.cell.2022.12.039 |pmid=36696902 |pmc=9911046 |biorxiv=10.1101/2022.07.19.500677 }}</ref>

The first discoveries of viroids in the 1970s triggered the historically third major extension of the [[biosphere]]—to include smaller lifelike entities—after the discoveries in 1675 by [[Antonie van Leeuwenhoek]] (of the "subvisible" microorganisms) and  in 1892–1898 by [[Dmitri Iosifovich Ivanovsky]] and [[Martinus Beijerinck]] (of the "submicroscopic" viruses). 
The unique properties of viroids have been recognized by the [[International Committee on Taxonomy of Viruses]],  in creating a new [[order (taxonomic rank)|order]] of [[subviral agents]].<ref>{{cite book | vauthors = King AM, Adams MJ, Carstens EB, Lefkovitz EJ, etal | title = Virus Taxonomy. Ninth Report of the International Committee for Virus Taxonomy. | location = Burlington, Massachusetts, US | publisher = Elsevier Academic Press | date = 2012 | pages = 1221–1259  | isbn = 978-0-12-384685-3  }}</ref>

The first recognized viroid, the pathogenic agent of the [[Potato spindle tuber viroid|potato spindle tuber disease]], was discovered, initially molecularly characterized, and named by [[Theodor Otto Diener]], plant pathologist at the U.S Department of Agriculture's Research Center in Beltsville, Maryland, in 1971.<ref name="pmid5095900">{{cite journal | vauthors = Diener TO | title = Potato spindle tuber "virus". IV. A replicating, low molecular weight RNA | journal = Virology | volume = 45 | issue = 2 | pages = 411–28 | date = August 1971 | pmid = 5095900 | doi = 10.1016/0042-6822(71)90342-4 }}</ref><ref name = "ARS_timeline">{{cite web|url=http://www.ars.usda.gov/is/timeline/viroid.htm |title=ARS Research Timeline – Tracking the Elusive Viroid |date=2006-03-02 |access-date=2007-07-18}}</ref> This viroid is now called potato spindle tuber viroid, abbreviated PSTVd.  The ''[[Citrus exocortis|Citrus exocortis viroid]]'' (CEVd)  was discovered soon thereafter, and together understanding of PSTVd and CEVd shaped the concept of the viroid.<ref name="pmid16078879">{{cite journal |vauthors=Flores R, Hernández C, Martínez de Alba AE, Daròs JA, Di Serio F |title=Viroids and viroid-host interactions |journal=Annual Review of Phytopathology |volume=43 |issue= |pages=117–39 |date=2005 |pmid=16078879 |doi=10.1146/annurev.phyto.43.040204.140243 |url=}}</ref>

Although viroids are composed of nucleic acid, they do not code for any [[protein]].<ref>{{cite journal | vauthors = Tsagris EM, Martínez de Alba AE, Gozmanova M, Kalantidis K | title = Viroids | journal = Cellular Microbiology | volume = 10 | issue = 11 | pages = 2168–79 | date = November 2008 | pmid = 18764915 | doi = 10.1111/j.1462-5822.2008.01231.x | s2cid = 221581424 | doi-access = free }}</ref><ref>{{cite journal| vauthors = Flores R, Di Serio F, Hernández C |title=Viroids: The Noncoding Genomes|journal=Seminars in Virology|date=February 1997|volume=8|issue=1|pages=65–73|doi=10.1006/smvy.1997.0107}}</ref> The viroid's replication mechanism uses [[RNA polymerase II]], a host cell enzyme normally associated with synthesis of [[messenger RNA]] from DNA, which instead catalyzes "[[rolling circle]]" synthesis of new RNA using the viroid's RNA as a template. Viroids are often [[ribozymes]], having [[catalytic]] properties that allow self-cleavage and ligation of unit-size genomes from larger replication intermediates.<ref name="pmid33800543">{{cite journal |vauthors=Moelling K, Broecker F |title=Viroids and the Origin of Life |journal=International Journal of Molecular Sciences |volume=22 |issue=7 |date=March 2021 |page=3476 |pmid=33800543 |pmc=8036462 |doi=10.3390/ijms22073476 |url=|doi-access=free }}</ref>

Diener initially hypothesized in 1989 that viroids may represent "living relics" from the widely assumed, ancient, and non-cellular [[RNA world]], and others have followed this conjecture.<ref name="Diener_1989">{{cite journal |vauthors=Diener TO |date=December 1989 |title=Circular RNAs: relics of precellular evolution? |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=86 |issue=23 |pages=9370–4 |bibcode=1989PNAS...86.9370D |doi=10.1073/pnas.86.23.9370 |pmc=298497 |pmid=2480600 |doi-access=free}}</ref><ref>{{cite journal|last1=Moelling|first1=Karin|last2=Broecker |first2=Felix|date=2021-03-28|title=Viroids and the Origin of Life|journal=International Journal of Molecular Sciences|volume=22|issue=7|pages=3476 |doi=10.3390/ijms22073476|issn=1422-0067 |pmc=8036462|pmid=33800543|doi-access=free}}</ref> Following the discovery of [[retrozyme]]s, it has been proposed that viroids and other viroid-like elements may derive from this newly found class of [[retrotransposon]].<ref name=":3">{{cite journal|last1=Cervera|first1=Amelia |last2=Urbina|first2=Denisse |last3=de la Peña|first3=Marcos|date=2016-06-23 |title=Retrozymes are a unique family of non-autonomous retrotransposons with hammerhead ribozymes that propagate in plants through circular RNAs |journal=Genome Biology|volume=17|issue=1|pages=135 |doi=10.1186/s13059-016-1002-4|issn=1474-760X|pmc=4918200|pmid=27339130 |doi-access=free }}</ref><ref name=":0">{{cite journal |last1=de la Peña|first1=Marcos|last2=Cervera|first2=Amelia|date=2017-08-03|title=Circular RNAs with hammerhead ribozymes encoded in eukaryotic genomes: The enemy at home|journal=RNA Biology |language=en|volume=14|issue=8 |pages=985–991|doi=10.1080/15476286.2017.1321730|issn=1547-6286 |pmc=5680766|pmid=28448743}}</ref><ref name=":1">{{cite journal|last1=Lee|first1=Benjamin D. |last2=Koonin |first2=Eugene V.|date=2022-01-12|title=Viroids and Viroid-like Circular RNAs: Do They Descend from Primordial Replicators?|journal=Life|volume=12|issue=1|pages=103 |doi=10.3390/life12010103|pmid=35054497 |pmc=8781251 |bibcode=2022Life...12..103L |issn=2075-1729|doi-access=free}}</ref>

The human pathogen [[hepatitis D virus]] is a subviral agent similar in structure to a viroid, as it is a hybrid particle enclosed by surface proteins from the [[hepatitis B virus]].<ref>{{cite journal | vauthors = Alves C, Branco C, Cunha C | title = Hepatitis delta virus: a peculiar virus | journal = Advances in Virology | volume = 2013 | pages = 560105 | year = 2013 | pmid = 24198831 | pmc = 3807834 | doi = 10.1155/2013/560105 | doi-access = free }}</ref>

==Taxonomy==
[[File:PSTviroid.png|thumb|center|800px|Putative [[Nucleic acid secondary structure|secondary structure]] of the PSTVd viroid. The highlighted nucleotides are found in most other viroids.]]

{{as of|2005}}:<ref name="pmid16078879"/>
*Family [[Pospiviroidae]]: relies on host Rnase III<ref name=Lee/>
**Genus ''[[Pospiviroid]]''; type species: ''[[Potato spindle tuber viroid]]'';  356–361 nucleotides(nt)<ref name=nt>{{cite book | title=Desk Encyclopedia of Plant and Fungal Virology | isbn=978-0123751485|editor=Brian W. J. Mahy, Marc H. V. Van Regenmortel | publisher= Academic Press|pages=71–81| date=2009-10-29}}</ref>
***''[[Tomato chlorotic dwarf viroid]]''; (TCDVd); accession AF162131, genome length 360nt
***''[[Mexican papita viroid]]''; (MPVd); accession L78454, genome length 360nt
***''[[Tomato planta macho viroid]]''; (TPMVd); accession K00817, genome length 360nt
***''[[Citrus exocortis|Citrus exocortis viroid]]''; 368–467 nt<ref name=nt />
***''[[Chrysanthemum stunt viroid]]''; (CSVd); accession V01107, genome length 356nt
***''[[Tomato apical stunt viroid]]''; (TASVd); accession K00818, genome length 360nt
***''[[Iresine 1 viroid]]''; (IrVd-1); accession X95734, genome length 370nt
***''[[Columnea latent viroid]]''; (CLVd); accession X15663, genome length 370nt
**Genus ''[[Hostuviroid]]''; type species: ''[[Hop stunt viroid]]''; 294–303 nt<ref name=nt/>
**Genus ''[[Cocadviroid]]''; type species: ''[[Coconut cadang-cadang viroid]]'';  246–247 nt<ref name=nt/>
***''[[Coconut tinangaja viroid]]''; (CTiVd); accession M20731, genome length 254nt
***''[[Hop latent viroid]]''; (HLVd); accession X07397, genome length 256nt
***''[[Citrus IV viroid]]''; (CVd-IV); accession X14638, genome length 284nt
**Genus ''[[Apscaviroid]]''; type species: ''[[Apple scar skin viroid]]''; 329–334 nt<ref name=nt/>
***''[[Citrus III viroid]]''; (CVd-III); accession AF184147, genome length 294nt
***''[[Apple dimple fruit viroid]]''; (ADFVd); accession X99487, genome length 306nt
***''[[Grapevine yellow speckle 1 viroid]]''; (GVYSd-1); accession X06904, genome length 367nt
***''[[Grapevine yellow speckle 2 viroid]]''; (GVYSd-2); accession J04348, genome length 363nt
***''[[Citrus bent leaf viroid]]''; (CBLVd); accession M74065, genome length 318nt
***''[[Pear blister canker viroid]]''; (PBCVd); accession D12823, genome length 315nt
***''[[Australian grapevine viroid]]''; (AGVd); accession X17101, genome length 369nt
**Genus ''[[Coleviroid]]''; type species: ''[[Coleus blumei viroid 1]]''; 248–251 nt<ref name=nt/>
***''[[Coleus blumei 2 viroid]]''; (CbVd-2); accession X95365, genome length 301nt
***''[[Coleus blumei 3 viroid]]''; (CbVd-3); accession X95364, genome length 361nt
*Family [[Avsunviroidae]]: autocatalytic clevage<ref name=Lee/>
**Genus ''[[Avsunviroid]]''; type species: ''[[Avocado sunblotch viroid]]''; 246–251 nt<ref name=nt/>
**Genus ''[[Pelamoviroid]]''; type species: ''[[Peach latent mosaic viroid]]''; 335–351 nt<ref name=nt/>
**Genus ''[[Elaviroid]]''; type species: ''[[Eggplant latent viroid]]''; 332–335 nt<ref name=nt/>

==Transmission and replication==
[[File:Viroids- how it do.gif|thumb|The reproduction mechanism of a typical viroid. Leaf contact transmits the viroid. The viroid enters the cell via its [[plasmodesmata]]. RNA polymerase II catalyzes rolling-circle synthesis of new viroids.]]
Viroids are only known to infect plants, and infectious viroids can be transmitted to new plant hosts by [[aphid]]s, by cross contamination following mechanical damage to plants as a result of horticultural or agricultural practices, or from plant to plant by leaf contact.<ref name=nt/><ref>{{cite journal | vauthors = De Bokx JA, Piron PG | year = 1981 | title = Transmission of potato spindle tuber viroid by aphids. | journal = Netherlands Journal of Plant Pathology | volume = 87 | issue = 2 | pages = 31–34 | doi=10.1007/bf01976653| s2cid = 44660564 }}</ref> Upon infection, viroids replicate in the nucleus (''Pospiviroidae'') or [[chloroplasts]] (''Avsunviroidae'') of plant cells in three steps through an RNA-based mechanism. They require [[RNA polymerase II]], a host cell enzyme normally associated with synthesis of [[messenger RNA]] from DNA, which instead catalyzes "[[rolling circle]]" synthesis of new RNA using the viroid as template.<ref name="pmid22719735">{{cite journal | vauthors = Flores R, Serra P, Minoia S, Di Serio F, Navarro B | title = Viroids: from genotype to phenotype just relying on RNA sequence and structural motifs | journal = Frontiers in Microbiology | volume = 3 | pages = 217 | year = 2012 | pmid = 22719735 | pmc = 3376415 | doi = 10.3389/fmicb.2012.00217 | doi-access = free }}</ref>

Unlike plant viruses which produce [[movement proteins]], viroids are entirely passive, relying entirely on the host. This is useful in the study of RNA kinetics in plants.<ref name="pmid16078879"/>

==RNA silencing==
There has long been uncertainty over how viroids induce [[symptom]]s in plants without encoding any [[protein]] products within their sequences.<ref name="pmid28738223">{{cite journal |vauthors=Flores R, Navarro B, Kovalskaya N, Hammond RW, Di Serio F |title=Engineering resistance against viroids |journal=Current Opinion in Virology |volume=26 |issue= |pages=1–7 |date=October 2017 |pmid=28738223 |doi=10.1016/j.coviro.2017.07.003}}</ref> Evidence suggests that [[RNA silencing]] is involved in the process. First, changes to the viroid [[genome]] can dramatically alter its [[virulence]].<ref name="pmid1546460">{{cite journal |vauthors=Hammond RW |title=Analysis of the virulence modulating region of potato spindle tuber viroid (PSTVd) by site-directed mutagenesis |journal=Virology |volume=187 |issue=2 |pages=654–662 |date=April 1992 |pmid=1546460 |doi=10.1016/0042-6822(92)90468-5 |url=https://zenodo.org/record/1258280}}</ref> This reflects the fact that any [[siRNA]]s produced would have less complementary [[base pairing]] with target [[messenger RNA]]. Secondly, [[siRNA]]s corresponding to sequences from viroid genomes have been isolated from infected plants. Finally, [[transgenic]] expression of the noninfectious [[Hairpin RNA|hpRNA]] of [[potato spindle tuber viroid]] develops all the corresponding viroid-like symptoms.<ref>{{cite journal |vauthors=Wang MB, Bian XY, Wu LM, Liu LX, Smith NA, Isenegger D, Wu RM, Masuta C, Vance VB, Watson JM, Rezaian A, Dennis ES, Waterhouse PM |display-authors=6 |title=On the role of RNA silencing in the pathogenicity and evolution of viroids and viral satellites |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=101 |issue=9 |pages=3275–3280 |date=March 2004 |pmid=14978267 |pmc=365780 |doi=10.1073/pnas.0400104101 |bibcode=2004PNAS..101.3275W |doi-access=free}}</ref> This indicates that when viroids replicate via a double stranded intermediate [[RNA]], they are targeted by a [[dicer]] enzyme and cleaved into siRNAs that are then loaded onto the [[RNA-induced silencing complex]]. The viroid siRNAs contain sequences capable of complementary base pairing with the plant's own messenger RNAs, and induction of degradation or inhibition of translation causes the classic viroid symptoms.<ref>{{cite book |vauthors=Pallas V, Martinez G, Gomez G |chapter=The Interaction Between Plant Viroid-Induced Symptoms and RNA Silencing |title=Antiviral Resistance in Plants |volume=894 |pages=323–343 |year=2012 |pmid=22678590 |doi=10.1007/978-1-61779-882-5_22 |isbn=978-1-61779-881-8 |series=Methods in Molecular Biology |hdl=10261/74632 |hdl-access=free}}</ref>

==Viroid-like elements==
"Viroid-like elements" refer to pieces of covalently closed circular (ccc) RNA molecules that do not share the viroid's lifecycle. The category encompasses satellite RNAs (including small plant satRNAs "[[virusoids]]", fungal "[[ambivirus]]", and the much larger [[Hepatitis D|HDV]]-like ''[[Ribozyviria]]'') and "retroviroids". Most of them also carry some type of a [[ribozyme]].<ref name=Lee/>

===Viroid-like satellite RNAs===
Viroid-like [[satellite RNA]]s are infectious circular RNA molecules that depend on a carrier virus to reproduce, being carried in their [[capsid]]s. Like Avsunviroidae, however, they are capable of self-clevage.<ref name=pmid35183574>{{cite journal |last1=Balázs |first1=E |last2=Hegedűs |first2=K |last3=Divéki |first3=Z |title=The unique carnation stunt-associated pararetroviroid. |journal=Virus Research |date=15 April 2022 |volume=312 |pages=198709 |doi=10.1016/j.virusres.2022.198709 |pmid=35183574|s2cid=246987005 }}</ref>

===Ambiviruses===
"Ambiviruses" are mobile genetic elements that were recently (2020s) discovered in [[fungi]]. Their RNA [[genome]]s are circular, circa 5 kb in length. One of at least two open reading frames encodes a viral RNA-directed [[RNA polymerase]], that firmly places "ambiviruses" into [[riboviria]]n kingdom ''[[Orthornavirae]]''; a separate phylum ''[[Ambiviricota]]'' has been established since the 2023 ICTV Virus Taxonomy Release because of the unique features of encoding RNA-directed RNA polymerases but also having divergent [[ribozyme]]s in various combinations in both sense and antisense orientation – the detection of circular forms in both sense orientations suggest that "ambiviruses" use rolling circle replication for propagation.<ref>{{cite journal |last1=Sutela |first1=Suvi |last2=Forgia |first2=Marco |last3=Vainio |first3=Eeva J |last4=Chiapello |first4=Marco |last5=Daghino |first5=Stefania |last6=Vallino |first6=Marta |last7=Martino |first7=Elena |last8=Girlanda |first8=Mariangela |last9=Perotto |first9=Silvia |last10=Turina |first10=Massimo |title=The virome from a collection of endomycorrhizal fungi reveals new viral taxa with unprecedented genome organization |journal=Virus Evolution |date=1 July 2020 |volume=6 |issue=2 |pages=veaa076 |doi=10.1093/ve/veaa076 |pmid=33324490 |pmc=7724248}}</ref><ref>{{cite journal |last1=Chong |first1=Li Chuin |last2=Lauber |first2=Chris |title=Viroid-like RNA-dependent RNA polymerase-encoding ambiviruses are abundant in complex fungi |journal=Frontiers in Microbiology |date=12 May 2023 |volume=14 |doi=10.3389/fmicb.2023.1144003 |doi-access=free |pmid=37275138 |pmc=10237039}}</ref><ref>{{cite web |title=ICTV Virus Taxonomy: 2023 Release |url=https://ictv.global/taxonomy |publisher=ICTV |access-date=2 May 2024}}</ref>

===Retroviroids===
"Retroviroids", more formally "retroviroid-like elements", are viroid-like circular RNA sequences that are also found with homologous copies in the [[DNA]] genome of the host.<ref name="daros">{{cite journal| vauthors=Daròs JA, Flores R| title=Identification of a retroviroid-like element from plants. | journal=Proceedings of the National Academy of Sciences of the United States of America | year= 1995 | volume= 92 | issue= 15 | pages= 6856–6860 | pmid= 7542779| doi= 10.1073/pnas.92.15.6856| pmc= 41428| bibcode=1995PNAS...92.6856D | doi-access=free }}</ref> The only types found are closely related to the original "carnation small viroid-like RNA" (CarSV).<ref name="pmid11172112">{{cite journal |vauthors=Hegedűs K, Palkovics L, Tóth EK, Dallmann G, Balázs E |title=The DNA form of a retroviroid-like element characterized in cultivated carnation species |journal=The Journal of General Virology |volume=82 |issue=Pt 3 |pages=687–691 |date=March 2001 |pmid=11172112 |doi=10.1099/0022-1317-82-3-687 |url=|doi-access=free }}</ref><ref name="hegedus">{{cite journal| vauthors= Hegedűs K, Dallmann G, Balázs E| title=The DNA form of a retroviroid-like element is involved in recombination events with itself and with the plant genome. | journal=Virology| year= 2004 | volume= 325 | issue= 2 | pages= 277–286 | pmid= 15246267| doi= 10.1016/j.virol.2004.04.035| pmc= | doi-access= free}}</ref> These elements may act as a [[sequence homology|homologous]] substrate upon which [[genetic recombination|recombination]] may occur and are linked to [[DNA repair#Double-strand breaks|double-stranded break repair]].<ref name="hegedus"/><ref name=Truong>{{cite journal | vauthors = Truong LN, Li Y, Shi LZ, Hwang PY, He J, Wang H, Razavian N, Berns MW, Wu X | display-authors = 6 | title = Microhomology-mediated End Joining and Homologous Recombination share the initial end resection step to repair DNA double-strand breaks in mammalian cells | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 110 | issue = 19 | pages = 7720–25 | date = May 2013 | pmid = 23610439 | pmc = 3651503 | doi = 10.1073/pnas.1213431110 | bibcode = 2013PNAS..110.7720T | doi-access = free }}</ref>

These elements are dubbed retroviroids as the homologous DNA is generated by [[reverse transcriptase]] that is encoded by [[retrovirus]]es.<ref name="Flores-2014"/><ref>{{cite book | vauthors = Hull R | chapter = Chapter 5: Agents Resembling or Altering Virus Diseases | chapter-url = https://books.google.com/books?id=PYrZAAAAQBAJ&pg=PA199 |title=Plant virology |date= October 2013 |location=London, UK | publisher = Academic Press |isbn=978-0-12-384872-7 |edition=Fifth}}</ref> They are neither true viroids nor viroid-like [[satellite RNA]]s: there is no extracellular form of these elements; instead, they are spread only through pollen or egg-cells.<ref name=pmid35183574/> They appear to co-occur with a [[pararetrovirus]].<ref>{{cite journal |last1=Breit |first1=TM |last2=de Leeuw |first2=WC |last3=van Olst |first3=M |last4=Ensink |first4=WA |last5=van Leeuwen |first5=S |last6=Dekker |first6=RJ |title=Genome Sequence of a New Carnation Small Viroid-Like RNA, CarSV-1. |journal=Microbiology Resource Announcements |date=16 March 2023 |volume=12 |issue=3 |pages=e0121922 |doi=10.1128/mra.01219-22 |pmid=36840552 |pmc=10019309 |doi-access=free}}</ref>

===Obelisks===
{{Main|Obelisk (biology)}}
After applying [[metatranscriptomics]] – the computer-aided search for RNA sequences and their analysis – biologists reported in January 2024 the discovery of "[[Obelisk (life form)|obelisks]]", a new class of viroid-like elements, and "oblins", their related group of proteins, in the [[human microbiome]]. Given that the RNA sequences recovered do not have [[Homology (biology)|homologies]] in any other known life form, the researchers suggest that the obelisks are distinct from viruses, viroids and viroid-like entities, and thus form an entirely new class of organisms.<ref name="SA-20240129">{{cite journal |last=Koumoundouros |first=Tessa |title='Obelisks': Entirely New Class of Life Has Been Found in The Human Digestive System |url=https://www.sciencealert.com/obelisks-entirely-new-class-of-life-has-been-found-in-the-human-digestive-system |date=29 January 2024 |journal=[[ScienceAlert]] |url-status=live |archiveurl=https://archive.today/20240129133614/https://www.sciencealert.com/obelisks-entirely-new-class-of-life-has-been-found-in-the-human-digestive-system |archivedate=29 January 2024 |accessdate=29 January 2024 }}</ref><ref name="BRX-20240121">{{cite journal |author=Zheludev, Ivan N. |display-authors=et al. |title=Viroid-like colonists of human microbiomes |url=https://www.biorxiv.org/content/10.1101/2024.01.20.576352v1 |date=21 January 2024 |journal=[[bioRxiv]] |doi=10.1101/2024.01.20.576352 |pmid=38293115 |pmc=10827157 |url-status=live |archiveurl=https://archive.today/20240129133518/https://www.biorxiv.org/content/10.1101/2024.01.20.576352v1 |archivedate=29 January 2024 |accessdate=29 January 2024 }}</ref>

==RNA world hypothesis==
Diener's 1989 hypothesis<ref>Diener, T O. "Circular RNAs: relics of precellular evolution?."Proc.Natl.Acad.Sci.USA, 1989;86(23):9370-9374</ref> had proposed that the unique properties of viroids make them more plausible macromolecules than [[intron]]s, or other RNAs considered in the past as possible "living relics" of a hypothetical, pre-cellular [[RNA world]]. If so, viroids have assumed significance beyond plant virology for evolutionary theory, because their properties make them more plausible candidates than other RNAs to perform crucial steps in the evolution of life from inanimate matter (abiogenesis).  Diener's hypothesis was mostly forgotten until 2014, when it was resurrected in a review article by Flores et al.,<ref name="Flores-2014">{{cite journal | vauthors = Flores R, Gago-Zachert S, Serra P, Sanjuán R, Elena SF | title = Viroids: survivors from the RNA world? | journal = Annual Review of Microbiology | volume = 68 | pages = 395–414 | date = June 18, 2014 | pmid = 25002087 | doi = 10.1146/annurev-micro-091313-103416 | url = https://digital.csic.es/bitstream/10261/107724/1/Annu.%20Rev.%20Microbiol.%20Flores%20et%20al%202014.pdf | hdl = 10261/107724 | hdl-access = free }}</ref> in which the authors summarized Diener's evidence supporting his hypothesis as:
# Viroids' small size, imposed by error-prone replication.
# Their high [[guanine]] and [[cytosine]] content, which increases stability and replication fidelity.
# Their circular structure, which assures complete replication without genomic tags.
# Existence of structural periodicity, which permits modular assembly into enlarged genomes.
# Their lack of protein-coding ability, consistent with a [[ribosome]]-free habitat.
# Replication mediated in some by [[ribozymes]]—the fingerprint of the RNA world.

The presence, in extant cells, of RNAs with molecular properties predicted for RNAs of the RNA world constitutes another powerful argument supporting the RNA world hypothesis. However, the origins of viroids themselves from this RNA world has been cast into doubt by several factors, including the discovery of [[retrozyme]]s (a family of [[retrotransposon]] likely representing their ancestors) and their complete absence from organisms outside of the [[plant]]s (especially their complete absence from [[prokaryote]]s including [[bacteria]] and [[archaea]]).<ref name=":3" /><ref name=":0" /><ref name=":1" /> However, recent studies suggest that the diversity of viroids and  others viroid-like elements is broader than previously thought and that it would not be limited to plants, encompassing even the [[prokaryotes]]. Matches between viroid cccRNAs and [[CRISPR]] spacers suggest that some of them might replicate in prokaryotes.<ref name=Lee/>

==Control==
The development of tests based on [[ELISA]], [[polymerase chain reaction|PCR]], and [[nucleic acid hybridization]] has allowed for rapid and inexpensive detection of known viroids in [[agricultural biosecurity inspection|biosecurity inspections]], [[phytosanitary inspection]]s, and [[agricultural quarantine|quarantine]].<ref name="pmid26047558"/>

==History==
In the 1920s, symptoms of a previously unknown potato disease were noticed in New York and New Jersey fields. Because tubers on affected plants become elongated and misshapen, they named it the potato spindle tuber disease.<ref>{{cite journal | vauthors = Owens RA, Verhoeven JT | title = Potato Spindle Tuber | journal = Plant Health Instructor | year = 2009 | doi = 10.1094/PHI-I-2009-0804-01 }}</ref>

The symptoms appeared on plants onto which pieces from affected plants had been budded—indicating that the disease was caused by a transmissible pathogenic agent. A [[fungus]] or [[Bacteria|bacterium]] could not be found consistently associated with symptom-bearing plants, however, and therefore, it was assumed the disease was caused by a virus. Despite numerous attempts over the years to isolate and purify the assumed virus, using increasingly sophisticated methods, these were unsuccessful when applied to extracts from potato spindle tuber disease-afflicted plants.<ref name = "ARS_timeline"/>

In 1971, Theodor O. Diener showed that the agent was not a virus, but a totally unexpected novel type of pathogen, 1/80th the size of typical viruses, for which he proposed the term "viroid".<ref name="pmid5095900"/> Parallel to agriculture-directed studies, more basic scientific research elucidated many of viroids' physical, chemical, and macromolecular properties. Viroids were shown to consist of short stretches (a few hundred nucleotides) of single-stranded RNA and, unlike viruses, did not have a protein coat. Viroids are extremely small, from 246 to 467 nucleotides, smaller than other infectious plant pathogens; they thus consist of fewer than 10,000 atoms. In comparison, the genomes of the smallest known viruses capable of causing an infection by themselves are around 2,000 nucleotides long.<ref name=Pommerville/>

In 1976, Sanger et al.<ref name="pmid1069269">{{cite journal | vauthors = Sanger HL, Klotz G, Riesner D, Gross HJ, Kleinschmidt AK | title = Viroids are single-stranded covalently closed circular RNA molecules existing as highly base-paired rod-like structures | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 73 | issue = 11 | pages = 3852–6 | date = November 1976 | pmid = 1069269 | pmc = 431239 | doi = 10.1073/pnas.73.11.3852 | bibcode = 1976PNAS...73.3852S | doi-access = free }}</ref> presented evidence that potato spindle tuber viroid is a "single-stranded, covalently closed, circular RNA molecule, existing as a highly base-paired rod-like structure"—believed to be the first such molecule described. Circular RNA, unlike linear RNA, forms a covalently closed continuous loop, in which the 3' and 5' ends present in linear RNA molecules have been joined. Sanger et al. also provided evidence for the true circularity of viroids by finding that the RNA could not be phosphorylated at the 5' terminus. In other tests, they failed to find even one free 3' end, which ruled out the possibility of the molecule having two 3' ends. Viroids thus are true circular RNAs.<ref name="pmid33460914">{{cite journal |vauthors=Wang Y |title=Current view and perspectives in viroid replication |journal=Current Opinion in Virology |volume=47 |issue= |pages=32–37 |date=April 2021 |pmid=33460914 |doi=10.1016/j.coviro.2020.12.004 |pmc=8068583 |url=}}</ref>

The single-strandedness and circularity of viroids was confirmed by electron microscopy,<ref name="pmid4728831">{{cite journal | vauthors = Sogo JM, Koller T, Diener TO | title = Potato spindle tuber viroid. X. Visualization and size determination by electron microscopy | journal = Virology | volume = 55 | issue = 1 | pages = 70–80 | date = September 1973 | pmid = 4728831 | doi = 10.1016/s0042-6822(73)81009-8 }}</ref> The complete nucleotide sequence of potato spindle tuber viroid was determined in 1978.<ref>{{cite journal | vauthors = Gross HJ, Domdey H, Lossow C, Jank P, Raba M, Alberty H, Sänger HL | title = Nucleotide sequence and secondary structure of potato spindle tuber viroid | journal = Nature | volume = 273 | issue = 5659 | pages = 203–8 | date = May 1978 | pmid = 643081 | doi = 10.1038/273203a0 | s2cid = 19398777 | bibcode = 1978Natur.273..203G }}</ref> PSTVd was the first pathogen of a eukaryotic organism for which the complete molecular structure has been established. Over thirty plant diseases have since been identified as viroid-, not virus-caused, as had been assumed.<ref name=Pommerville>{{cite book |last=Pommerville|first=Jeffrey C |date=2014 |title= Fundamentals of Microbiology|location=Burlington, MA |publisher= Jones and Bartlett Learning |page= 482|isbn=978-1-284-03968-9}}</ref><ref name="Hammond_2006">{{cite journal | vauthors = Hammond RW, Owens RA | title = Viroids: New and Continuing Risks for Horticultural and Agricultural Crops. | journal = APSnet Feature Articles | date = 2006 | doi = 10.1094/APSnetFeature-2006-1106 }}</ref>

Four additional viroids or viroid-like RNA particles were discovered between 2009 and 2015.<ref name="pmid26047558">{{cite journal |vauthors=Wu Q, Ding SW, Zhang Y, Zhu S |title=Identification of viruses and viroids by next-generation sequencing and homology-dependent and homology-independent algorithms |journal=Annual Review of Phytopathology |volume=53 |issue= |pages=425–44 |date=2015 |pmid=26047558 |doi=10.1146/annurev-phyto-080614-120030 |url=|doi-access=free }}</ref>

In 2014, ''[[New York Times]]'' science writer Carl Zimmer published a popularized piece that mistakenly credited Flores et al. with the hypothesis' original conception.<ref name= Zimmer>{{cite news |last=Zimmer |first=C |author-link=Carl Zimmer |title=A Tiny Emissary From the Ancient Past |url=https://www.nytimes.com/2014/09/25/science/a-tiny-emissary-from-the-ancient-past.html |date=September 25, 2014 |work=[[New York Times]] |access-date=November 22, 2014 }}</ref>

In January 2024, biologists reported the discovery of "[[Obelisk (life form)|obelisks]]", a new class of viroid-like elements, and "oblins", their related group of proteins, in the [[human microbiome]].<ref name="SA-20240129" /><ref name="BRX-20240121" />

== See also ==
{{Portal|Biology|Medicine|Viruses}}
{{cmn|colwidth=15em|
* [[Circular RNA]]
* [[Microparasite]]
* [[Non-cellular life]]
* [[Obelisk (life form)]]
* [[Plant pathology]]
* [[Plasmid]]
* [[Prion]]
* [[RNA world hypothesis]]
* [[Satellite (biology)]]
* [[Virus]]
* [[Virus classification]]
* [[Virusoid]]
}}

== References ==
{{Reflist|35em}}

== External links ==
* [http://www.atsu.edu/faculty/chamberlain/Website/Lects/Prions.htm Viroids/ATSU]
* [https://viroids.org/ ViroidDB], a database of viroids and viroid-like circular RNAs

{{Self-replicating organic structures}}
{{Organisms et al.}}
{{Taxonbar|from=Q209917}}
{{Authority control}}

[[Category:Viroids| ]]
[[Category:Subviral agents]]