{{short description|Species of virus}} {{For|the computer virus (the ILOVEYOU virus)|ILOVEYOU}} {{Use dmy dates|date=August 2019}} {{Virusbox | parent = Cuevavirus | species = Lloviu cuevavirus | subdivision_ranks = Member virus | subdivision = Lloviu virus (LLOV) }}
The species '''''Lloviu cuevavirus''''' ({{IPAc-en|ˈ|j|ɒ|v|j|uː|_|ˌ|k|w|ɛ|v|ə|ˈ|v|aɪ|r|ə|s}} {{respell|YOV|ew|_|KWEV|ə|VY|rəs}}) is the taxonomic home of a virus that forms filamentous virion, ''Lloviu virus'' (LLOV). The species is included in the genus ''Cuevavirus''.<ref name="KuhnArch">{{Cite journal | last1 = Kuhn | first1 = J. H. | last2 = Becker | first2 = S. | last3 = Ebihara | first3 = H. | last4 = Geisbert | first4 = T. W. | last5 = Johnson | first5 = K. M. | last6 = Kawaoka | first6 = Y. | last7 = Lipkin | first7 = W. I. | last8 = Negredo | first8 = A. I. | last9 = Netesov | first9 = S. V. | last10 = Nichol | first10 = S. T. | last11 = Palacios | first11 = G. | last12 = Peters | first12 = C. J. | last13 = Tenorio | first13 = A. | last14 = Volchkov | first14 = V. E. | last15 = Jahrling | first15 = P. B. | title = Proposal for a revised taxonomy of the family Filoviridae: Classification, names of taxa and viruses, and virus abbreviations | doi = 10.1007/s00705-010-0814-x | journal = Archives of Virology | volume = 155 | issue = 12 | pages = 2083–2103 | pmc = 3074192 | year = 2010 | pmid = 21046175 }}</ref><ref name="Negredo2011">{{Cite journal | last1 = Negredo | first1 = A. | last2 = Palacios | first2 = G. | last3 = Vázquez-Morón | first3 = S. | last4 = González | first4 = F. L. | last5 = Dopazo | first5 = H. N. | last6 = Molero | first6 = F. | last7 = Juste | first7 = J. | last8 = Quetglas | first8 = J. | last9 = Savji | first9 = N. | author10 = de la Cruz Martínez M | last11 = Herrera | first11 = J. E. | last12 = Pizarro | first12 = M. | last13 = Hutchison | first13 = S. K. | last14 = Echevarría | first14 = J. E. | last15 = Lipkin | first15 = W. I. | last16 = Tenorio | first16 = A. | editor1-last = Basler | editor1-first = Christopher F | title = Discovery of an Ebolavirus-Like Filovirus in Europe | doi = 10.1371/journal.ppat.1002304 | journal = PLOS Pathogens | volume = 7 | issue = 10 | article-number = e1002304 | year = 2011 | pmid = 22039362 | pmc =3197594 | doi-access = free }}</ref> LLOV is a distant relative of the commonly known Ebola virus and Marburg virus.
==Use of term== The species ''Lloviu cuevavirus'' is a virological taxon (i.e. a man-made concept) included in the genus ''Cuevavirus'', family ''Filoviridae'', order ''Mononegavirales''.<ref name=KuhnArch/> The species has a single virus member, Lloviu virus.<ref name=KuhnArch/> Lloviu virus is the sole member of the species ''Lloviu cuevavirus'', which is included genus ''Cuevavirus'', family ''Filoviridae'', order ''Mononegavirales''.<ref name="KuhnArch" /><ref name="Negredo2011" /> The name Lloviu virus is derived from ''Cueva del Lloviu'' (the name of a Spanish cave in which it was first discovered<ref name="KuhnArch" />) and the taxonomic suffix ''virus'' (which denotes a virus species).<ref name=KuhnArch/>
In 2010, the species and the genus ''cuevavirus'' were proposed as independent species and genus.<ref name=KuhnArch/> In July 2013, the species and the genus ''cuevavirus'' were ratified by the International Committee on Taxonomy of Viruses (ICTV) to be included in its report, therefore the name is now to be italicized.<ref>{{cite web|title=ICTV Taxonomy History for ''Lloviu cuevavirus''|url=http://www.ictvonline.org/taxonomyHistory.asp?taxnode_id=20140725&taxa_name=Lloviu%20cuevavirus|website=International Committee on Taxonomy of Viruses|access-date=7 March 2015}}</ref>
==Species inclusion criteria== A virus that fulfills the criteria for being a member of the genus "''Cuevavirus''" is a member of the species "Lloviu cuevavirus" if it has the properties of "''cuevaviruses''" (because there is currently only "cuevavirus" species) and if its genome differs from that of Lloviu virus (variant Bat86) by <30% at the nucleotide level.<ref name=KuhnArch/>
'''Lloviu virus''' ({{IPAc-en|ˈ|j|ɒ|v|j|uː}} {{respell|YOV|yoo}};<ref name=KuhnArch/> '''LLOV''') is a virus distantly related to the well-known pathogens Ebola virus and Marburg virus.<ref name="KuhnArch"/><ref name="Negredo2011"/>
==History== LLOV was discovered in 2011 in Schreibers's long-fingered bats (species ''Miniopterus schreibersii'') that were found dead in Cueva del Lloviu in 2002, Asturias, Spain, as well as in caves in Spanish Cantabria and in caves in France and Portugal.<ref name=Negredo2011/> It has not yet been proven that the virus is the etiological agent of a novel bat disease, but healthy Schreibers' long-fingered bats were not found to contain traces of the viruses, thereby at least suggesting that the virus may be pathogenic for certain bats. Necropsies of dead bats did not reveal macroscopic pathology, but microscopic examination suggested viral pneumonia.<ref name=Negredo2011/> No information is available about whether or not LLOV infects humans.<ref>{{cite journal |title=Ebola: Lessons on Vaccine Development |author=Heinz Feldmann |author2=Friederike Feldmann |author3=Andrea Marzi |journal=Annual Review of Microbiology |volume=72 |pages=423–46 |year=2018 |doi=10.1146/annurev-micro-090817-062414|pmid=30200851 |s2cid=52185735 |pmc=11059209 }}</ref>
Seroreactivity of additional Schreibers's long-fingered bats were reported from North Spain from 2015, suggesting the circulation of the virus among those bat colonies. However PCR positive animals were not found.<ref>{{Cite journal|last1=Ramírez de Arellano|first1=Eva|last2=Sanchez-Lockhart|first2=Mariano|last3=Perteguer|first3=Maria J.|last4=Bartlett|first4=Maggie|last5=Ortiz|first5=Marta|last6=Campioli|first6=Pamela|last7=Hernández|first7=Ana|last8=Gonzalez|first8=Jeanette|last9=Garcia|first9=Karla|last10=Ramos|first10=Manolo|last11=Jiménez-Clavero|first11=Miguel Ángel|date=2019-04-19|title=First Evidence of Antibodies Against Lloviu Virus in Schreiber's Bent-Winged Insectivorous Bats Demonstrate a Wide Circulation of the Virus in Spain|journal=Viruses|volume=11|issue=4|page=360|doi=10.3390/v11040360|issn=1999-4915|pmc=6521100|pmid=31010201|doi-access=free}}</ref>
Additional Schreibers's long-fingered bat die-off events were reported from Hungary in 2013, 2016 and 2017. The presence of LLOV was confirmed in bat carcasses from 2016, presenting hemorrhagic symptoms.<ref>{{Cite journal|last1=Kemenesi|first1=Gábor|last2=Kurucz|first2=Kornélia|last3=Dallos|first3=Bianka|last4=Zana|first4=Brigitta|last5=Földes|first5=Fanni|last6=Boldogh|first6=Sándor|last7=Görföl|first7=Tamás|last8=Carroll|first8=Miles W|last9=Jakab|first9=Ferenc|date=2018-04-18|title=Re-emergence of Lloviu virus in Miniopterus schreibersii bats, Hungary, 2016|journal=Emerging Microbes & Infections|volume=7|issue=1|page=66|doi=10.1038/s41426-018-0067-4|issn=2222-1751|pmc=5906664|pmid=29670087}}</ref> Updated genome data was obtained from the Hungarian samples in 2020, using the Nanopore sequencing technique.<ref>{{Cite web|title=Historical moment in #filovirus research, sequencing the complete genome of #lloviuvirus in 50 minutes after a decade. @nanopore @TthGborEndre1 #filoviridae #emergingdisease #bat #virologypic.twitter.com/4a5fiWaIuz|url=https://twitter.com/GaborKemenesi/status/1267104764925534211|last=Kemenesi|first=Gabor|date=2020-05-31|website=@GaborKemenesi|language=en|access-date=2020-06-01}}</ref> The infectious virus was isolated from Schreibers's long-fingered bat in Hungary, making it only the third filovirus along with Marburg and Ravn viruses ever isolated from bats.<ref name=":0">{{Cite journal |last1=Kemenesi |first1=Gábor |last2=Tóth |first2=Gábor E. |last3=Mayora-Neto |first3=Martin |last4=Scott |first4=Simon |last5=Temperton |first5=Nigel |last6=Wright |first6=Edward |last7=Mühlberger |first7=Elke |last8=Hume |first8=Adam J. |last9=Suder |first9=Ellen L. |last10=Zana |first10=Brigitta |last11=Boldogh |first11=Sándor A. |date=2022-03-31 |title=Isolation of infectious Lloviu virus from Schreiber's bats in Hungary |journal=Nature Communications |language=en |volume=13 |issue=1 |page=1706 |doi=10.1038/s41467-022-29298-1|pmid=35361761 |pmc=8971391 |bibcode=2022NatCo..13.1706K |issn=2041-1723}}</ref>
==Virology==
===Genome=== Although LLOV was isolated in tissue culture, yet its genome has been determined in its entirety with exception of the 3' and 5' UTRs.<ref name=Negredo2011/><ref name=":0" /> Like all mononegaviruses, LLOV virions contain a non-infectious, linear nonsegmented, single-stranded RNA genome of negative polarity that most likely possesses inverse-complementary 3' and 5' termini, does not possess a 5' cap, is not polyadenylated, and is not covalently linked to a protein.<ref name=King2011>{{Citation|last1=Easton|first1=A.|last2=Pringle|first2=C. R.|chapter=Order Mononegavirales|year=2011|editor-last=King|editor-first=Andrew M. Q.|editor2-last=Adams|editor2-first=Michael J.|editor3-last=Carstens|editor3-first=Eric B.|display-editors = 3 |editor4-last=Lefkowitz|editor4-first=Elliot J.|title=Virus Taxonomy—Ninth Report of the International Committee on Taxonomy of Viruses|pages=653–657|publisher=Elsevier/Academic Press|location=London, UK|isbn=978-0-12-384684-6}}</ref> The LLOV genome is probably approximately 19 kb long and contains seven genes in the order 3'-UTR-''NP''-''VP35''-''VP40''-''GP''-''VP30''-''VP24''-''L''-5'-UTR. In contrast to ebolaviruses and Marburgviruses, which synthesize seven mRNAs to express the seven structural proteins, LLOV seems to produce only six mRNAs, i.e. one mRNA (''VP24''/''L'') is thought to be bicistronic. LLOV genomic transcriptional termination sites are identical to those of ebolavirus genomes but different from those of Marburgvirus genomes. LLOV transcriptional initiation sites are unique.<ref name=Negredo2011/>
===Replication=== The LLOV life cycle is hypothesized to begin with virion attachment to specific cell-surface receptors, followed by internalization, fusion of the virion envelope with endosomal membranes and the concomitant release of the virus nucleocapsid into the cytosol. LLOV glycoprotein (GP) is cleaved by endosomal cysteine proteases (cathepsins) and the cleaved glycoprotein interacts with the intracellular entry receptor, Niemann-Pick C1 (NPC1).<ref>{{cite journal |vauthors=Ng M, Ndungo E, Jangra RK, Cai Y, Postnikova E, Radoshitzky SR, Dye JM, Ramirez de Arellano E, Negredo A, Palacios G, Kuhn JH, Chandran K | date = 2014 | title = Cell entry by a novel European filovirus requires host endosomal cysteine proteases and Niemann–PickC1 | journal = Virology | pages = 637–46 | pmid = 25310500 | doi = 10.1016/j.virol.2014.08.019 | volume=468–470 | pmc=4252868}}</ref> The virus RdRp would partially uncoat the nucleocapsid and transcribe the genes into positive-stranded mRNAs, which would then be translated into structural and nonstructural proteins. LLOV L would bind to a single promoter located at the 3' end of the genome. Transcription would either terminate after a gene or continue to the next gene downstream. This means that genes close to the 3' end of the genome would be transcribed in the greatest abundance, whereas those toward the 5' end would be least likely to be transcribed. The gene order would therefore be a simple but effective form of transcriptional regulation. The most abundant protein produced would be the nucleoprotein, whose concentration in the cell would determine when L switches from gene transcription to genome replication. Replication would result in full-length, positive-stranded antigenomes that would in turn be transcribed into negative-stranded virus progeny genome copies. Newly synthesized structural proteins and genomes would self-assemble and accumulate near the inside of the cell membrane. Virions would bud off from the cell, gaining their envelopes from the cellular membrane they bud from. The mature progeny particles would then infect other cells to repeat the cycle.<ref name=King2011/>
==References== {{reflist}}
==External links== {{Wikispecies}} * [https://ictv.global/ International Committee on Taxonomy of Viruses (ICTV)]
{{Taxonbar|from1=Q20003768|from2=Q6662207}} {{filoviridae}}
Category:Bat virome Category:Arthropod-borne viral fevers and viral haemorrhagic fevers Category:Biological agents Category:Hemorrhagic fevers Category:Tropical diseases Category:Viral diseases Category:Virus-related cutaneous conditions Category:Filoviridae Category:Zoonotic viral diseases Category:Animal viral diseases