The species ''Lloviu cuevavirus'' ( ) is the

taxonomic 280px, Generalized scheme of taxonomy Taxonomy is a practice and science concerned with classification or categorization. Typically, there are two parts to it: the development of an underlying scheme of classes (a taxonomy) and the allocation ...

home of a virus that forms filamentous virion, ''Lloviu virus'' (LLOV). The species is included in the genus ''

Cuevavirus The species ''Lloviu cuevavirus'' ( ) is the taxonomic home of a virus that forms filamentous virion, ''Lloviu virus'' (LLOV). The species is included in the genus '' Cuevavirus''. LLOV is a distant relative of the commonly known Ebola virus a ...

''. LLOV is a distant relative of the commonly known

Ebola virus ''Orthoebolavirus zairense'' or Zaire ebolavirus, more commonly known as Ebola virus (; EBOV), is one of six known species within the genus ''Ebolavirus''. Four of the six known ebolaviruses, including EBOV, cause a severe and often fatal vira ...

and

Marburg virus Marburg virus (MARV) is a hemorrhagic fever virus of the '' Filoviridae'' family of viruses and a member of the species '' Marburg marburgvirus'', genus '' Marburgvirus''. It causes Marburg virus disease in primates, a form of viral hemorrhag ...

Use of term

The

species A species () is often defined as the largest group of organisms in which any two individuals of the appropriate sexes or mating types can produce fertile offspring, typically by sexual reproduction. It is the basic unit of Taxonomy (biology), ...

''Lloviu cuevavirus'' is a virological taxon (i.e. a man-made

concept A concept is an abstract idea that serves as a foundation for more concrete principles, thoughts, and beliefs. Concepts play an important role in all aspects of cognition. As such, concepts are studied within such disciplines as linguistics, ...

) included in the genus ''

'', family ''

Filoviridae ''Filoviridae'' () is a International Committee on Taxonomy of Viruses, family of RNA virus#Group_V_–_negative-sense_ssRNA_viruses, single-stranded negative-sense RNA viruses in the order (biology), order ''Mononegavirales''. Two members of the ...

'', order ''

Mononegavirales ''Mononegavirales'' is an order of negative-strand RNA viruses which have nonsegmented genomes. Some members that cause human disease in this order include Ebola virus, human respiratory syncytial virus, measles virus, mumps virus, Nipah viru ...

''. The species has a single

virus A virus is a submicroscopic infectious agent that replicates only inside the living Cell (biology), cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Viruses are ...

member, Lloviu virus. Lloviu virus is the sole member of the species ''Lloviu cuevavirus'', which is included genus ''

'',

family Family (from ) is a Social group, group of people related either by consanguinity (by recognized birth) or Affinity (law), affinity (by marriage or other relationship). It forms the basis for social order. Ideally, families offer predictabili ...

'',

order Order, ORDER or Orders may refer to: * A socio-political or established or existing order, e.g. World order, Ancien Regime, Pax Britannica * Categorization, the process in which ideas and objects are recognized, differentiated, and understood ...

''. The name Lloviu virus is derived from ''Cueva del Lloviu'' (the name of a

Spanish Spanish might refer to: * Items from or related to Spain: **Spaniards are a nation and ethnic group indigenous to Spain **Spanish language, spoken in Spain and many countries in the Americas **Spanish cuisine **Spanish history **Spanish culture ...

cave Caves or caverns are natural voids under the Earth's Planetary surface, surface. Caves often form by the weathering of rock and often extend deep underground. Exogene caves are smaller openings that extend a relatively short distance undergrou ...

in which it was first discovered) and the

suffix In linguistics, a suffix is an affix which is placed after the stem of a word. Common examples are case endings, which indicate the grammatical case of nouns and adjectives, and verb endings, which form the conjugation of verbs. Suffixes can ca ...

''virus'' (which denotes a virus species). In 2010, the species and the genus ''

cuevavirus The species ''Lloviu cuevavirus'' ( ) is the taxonomic home of a virus that forms filamentous virion, ''Lloviu virus'' (LLOV). The species is included in the genus '' Cuevavirus''. LLOV is a distant relative of the commonly known Ebola virus a ...

'' were proposed as independent species and genus. In July 2013, the species and the genus ''

'' were ratified by the

International Committee on Taxonomy of Viruses The International Committee on Taxonomy of Viruses (ICTV) authorizes and organizes the taxonomic classification of and the nomenclature for viruses. The ICTV develops a universal taxonomic scheme for viruses, and thus has the means to appropri ...

(ICTV) to be included in its report, therefore the name is now to be italicized.

Species inclusion criteria

A virus that fulfills the criteria for being a member of the genus "''

''" is a member of the species "Lloviu cuevavirus" if it has the properties of "''cuevaviruses''" (because there is currently only "

" species) and if its genome differs from that of Lloviu virus (variant Bat86) by <30% at the nucleotide level. Lloviu virus ( ; LLOV) is a virus distantly related to the well-known pathogens

and

. According to the rules for taxon naming established by the

(ICTV), the name Lloviu virus is always to be

capitalized Capitalization ( North American spelling; also British spelling in Oxford) or capitalisation (Commonwealth English; all other meanings) is writing a word with its first letter as a capital letter (uppercase letter) and the remaining letters in ...

(because "Lloviu" is a proper noun), but is never italicized, and may be

abbreviated An abbreviation () is a shortened form of a word or phrase, by any method including shortening, contraction, initialism (which includes acronym), or crasis. An abbreviation may be a shortened form of a word, usually ended with a trailing per ...

(with LLOV being the official abbreviation).

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 Asturias (; ; ) officially the Principality of Asturias, is an autonomous communities of Spain, autonomous community in northwest Spain. It is coextensive with the provinces of Spain, province of Asturias and contains some of the territory t ...

Spain Spain, or the Kingdom of Spain, is a country in Southern Europe, Southern and Western Europe with territories in North Africa. Featuring the Punta de Tarifa, southernmost point of continental Europe, it is the largest country in Southern Eur ...

, as well as in caves in Spanish

Cantabria Cantabria (, ; ) is an autonomous community and Provinces of Spain, province in northern Spain with Santander, Cantabria, Santander as its capital city. It is called a , a Nationalities and regions of Spain, historic community, in its current ...

and in caves in

France France, officially the French Republic, is a country located primarily in Western Europe. Overseas France, Its overseas regions and territories include French Guiana in South America, Saint Pierre and Miquelon in the Atlantic Ocean#North Atlan ...

and

Portugal Portugal, officially the Portuguese Republic, is a country on the Iberian Peninsula in Southwestern Europe. Featuring Cabo da Roca, the westernmost point in continental Europe, Portugal borders Spain to its north and east, with which it share ...

. It has not yet been proven that the virus is the

etiological Etiology (; alternatively spelled aetiology or ætiology) is the study of causation or origination. The word is derived from the Greek word ''()'', meaning "giving a reason for" (). More completely, etiology is the study of the causes, origin ...

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

pathogen In biology, a pathogen (, "suffering", "passion" and , "producer of"), in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a Germ theory of d ...

ic for certain bats. Necropsies of dead bats did not reveal

macroscopic The macroscopic scale is the length scale on which objects or phenomena are large enough to be visible with the naked eye, without magnifying optical instruments. It is the opposite of microscopic. Overview When applied to physical phenome ...

pathology Pathology is the study of disease. The word ''pathology'' also refers to the study of disease in general, incorporating a wide range of biology research fields and medical practices. However, when used in the context of modern medical treatme ...

, but

microscopic The microscopic scale () is the scale of objects and events smaller than those that can easily be seen by the naked eye, requiring a lens or microscope to see them clearly. In physics, the microscopic scale is sometimes regarded as the scale betwe ...

examination suggested

viral pneumonia Viral pneumonia is a pneumonia caused by a virus. Pneumonia is an infection that causes inflammation in one or both lungs. The pulmonary alveoli fill with fluid or pus making it difficult to breathe. Pneumonia can be caused by bacteria, viruses, ...

. No information is available about whether or not LLOV infects humans. However, Cueva del Lloviu is frequented by

tourists Tourism is travel for pleasure, and the Commerce, commercial activity of providing and supporting such travel. World Tourism Organization, UN Tourism defines tourism more generally, in terms which go "beyond the common perception of tourism as ...

and no human infections or disease has yet been observed, suggesting that it is possible that LLOV might be the second

filovirus ''Filoviridae'' () is a family of single-stranded negative-sense RNA viruses in the order ''Mononegavirales''. Two members of the family that are commonly known are Ebola virus and Marburg virus. Both viruses, and some of their lesser known rela ...

that is not pathogenic for humans (the first one being Reston virus (RESTV)). 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. Additional Schreibers's long-fingered bat die-off events were reported from

Hungary Hungary is a landlocked country in Central Europe. Spanning much of the Pannonian Basin, Carpathian Basin, it is bordered by Slovakia to the north, Ukraine to the northeast, Romania to the east and southeast, Serbia to the south, Croatia and ...

in 2013, 2016 and 2017. The presence of LLOV was confirmed in bat carcasses from 2016, presenting hemorrhagic symptoms. Updated genome data was obtained from the Hungarian samples in 2020, using the

Nanopore sequencing Nanopore sequencing is a third generation approach used in the sequencing of biopolymers — specifically, polynucleotides in the form of DNA or RNA. Nanopore sequencing allows a single molecule of DNA or RNA be sequenced without PCR amplif ...

technique. The infectious virus was isolated from Schreibers's long-fingered bat in Hungary, making it only the third filovirus along with

Marburg Marburg (; ) is a college town, university town in the States of Germany, German federal state () of Hesse, capital of the Marburg-Biedenkopf Districts of Germany, district (). The town area spreads along the valley of the river Lahn and has ...

and Ravn viruses ever isolated from bats.

Virology

Genome

Although LLOV was isolated in

tissue culture Tissue culture is the growth of tissue (biology), tissues or cell (biology), cells in an artificial medium separate from the parent organism. This technique is also called micropropagation. This is typically facilitated via use of a liquid, semi-s ...

, yet its genome has been determined in its entirety with exception of the 3' and 5' UTRs. Like all mononegaviruses, LLOV virions contain a non-infectious, linear nonsegmented, single-stranded

RNA Ribonucleic acid (RNA) is a polymeric molecule that is essential for most biological functions, either by performing the function itself (non-coding RNA) or by forming a template for the production of proteins (messenger RNA). RNA and deoxyrib ...

genome A genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding genes, other functional regions of the genome such as ...

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 Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

. The LLOV genome is probably approximately 19 kb long and contains seven

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

s in the order 3'-UTR-''NP''-''VP35''-''VP40''-''GP''-''VP30''-''VP24''-''L''- 5'-UTR. In contrast to

ebolavirus The genus ''Ebolavirus'' (- or ; - or ) is a International Committee on Taxonomy of Viruses, virological taxon included in the family ''Filoviridae'' (filament-shaped viruses), order ''Mononegavirales''. The members of this genus are called ebo ...

es and

Marburgvirus The genus ''Marburgvirus'' is the taxonomic home of ''Marburg marburgvirus'', whose members are the two known marburgviruses, Marburg virus (MARV) and Ravn virus (RAVV). Both viruses cause Marburg virus disease in humans and nonhuman primat ...

es, 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

genomes but different from those of

genomes. LLOV transcriptional initiation sites are unique.

Replication

The LLOV life cycle is hypothesized to begin with virion attachment to specific cell-surface

receptors Receptor may refer to: *Sensory receptor, in physiology, any neurite structure that, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds ...

, followed by internalization, fusion of the virion envelope with endosomal membranes and the concomitant release of the virus

nucleocapsid A capsid is the protein shell of a virus, enclosing its genetic material. It consists of several oligomeric (repeating) structural subunits made of protein called protomers. The observable 3-dimensional morphological subunits, which may or ma ...

into the

cytosol The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells ( intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondri ...

. LLOV glycoprotein (GP) is cleaved by endosomal cysteine proteases (

cathepsin Cathepsins (Ancient Greek ''kata-'' "down" and ''hepsein'' "boil"; abbreviated CTS) are proteases (enzymes that degrade proteins) found in all animals as well as other organisms. There are approximately a dozen members of this family, which are d ...

s) and the cleaved glycoprotein interacts with the intracellular entry receptor, Niemann-Pick C1 (

NPC1 Niemann-Pick disease, type C1 (NPC1) is a membrane protein that mediates intracellular cholesterol trafficking in mammals. In humans the protein is encoded by the ''NPC1'' gene (chromosome location 18q11). Function ''NPC1'' was identified as ...

). The virus RdRp would partially uncoat the nucleocapsid and transcribe the

genes In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

into positive-stranded

mRNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein. mRNA is ...

s, which would then be translated into structural and nonstructural

proteins Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, re ...

. 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 Nucleoproteins are proteins conjugated with nucleic acids (either DNA or RNA). Typical nucleoproteins include ribosomes, nucleosomes and viral nucleocapsid proteins. Structures Nucleoproteins tend to be positively charged, facilitating inte ...

, whose

concentration In chemistry, concentration is the abundance of a constituent divided by the total volume of a mixture. Several types of mathematical description can be distinguished: '' mass concentration'', '' molar concentration'', '' number 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 The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extr ...

. Virions would

bud In botany, a bud is an undeveloped or Plant embryogenesis, embryonic Shoot (botany), shoot and normally occurs in the axil of a leaf or at the tip of a Plant stem, stem. Once formed, a bud may remain for some time in a dormancy, dormant conditi ...

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.

References

External links

International Committee on Taxonomy of Viruses (ICTV)
{{filoviridae Bat virome Arthropod-borne viral fevers and viral haemorrhagic fevers Biological agents Hemorrhagic fevers Tropical diseases Viral diseases Virus-related cutaneous conditions Filoviridae Zoonotic viral diseases Animal viral diseases