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 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 ''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 hemorrhagic fever in humans and o ...

and Marburg virus.

Use of term

The

species In biology, a species is the basic unit of classification and a taxonomic rank of an organism, as well as a unit of biodiversity. A species is often defined as the largest group of organisms in which any two individuals of the appropriate s ...

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

concept Concepts are defined as abstract ideas. They are understood to be the fundamental building blocks of the concept behind principles, thoughts and beliefs. They play an important role in all aspects of cognition. As such, concepts are studied by ...

) included in the genus ''

'', family ''

Filoviridae ''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 re ...

'', order ''

Mononegavirales ''Mononegavirales'' is an order of negative-strand RNA viruses which have nonsegmented genomes. Some common members of the order are Ebola virus, human respiratory syncytial virus, measles virus, mumps virus, Nipah virus, and rabies virus. A ...

''. The species has a single

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

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

'',

family Family (from la, familia) is a group of people related either by consanguinity (by recognized birth) or affinity (by marriage or other relationship). The purpose of the family is to maintain the well-being of its members and of society. Idea ...

'', order ''

''. 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 Latin American countries **Spanish cuisine Other places * Spanish, Ontario, Can ...

cave A cave or cavern is a natural void in the ground, specifically a space large enough for a human to enter. Caves often form by the weathering of rock and often extend deep underground. The word ''cave'' can refer to smaller openings such as sea ...

in which it was first discovered) and the taxonomic suffix ''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 nomenclatures for viruses. The ICTV has developed a universal taxonomic scheme for viruses, and thus has the means to ap ...

(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 Marburg virus. According to the rules for taxon naming established by the

(ICTV), the name Lloviu virus is always to be capitalized (because "Lloviu" is a proper noun), but is never

italicized In typography, italic type is a cursive font based on a stylised form of calligraphic handwriting. Owing to the influence from calligraphy, italics normally slant slightly to the right. Italics are a way to emphasise key points in a printed tex ...

, and may be

abbreviated An abbreviation (from Latin ''brevis'', meaning ''short'') is a shortened form of a word or phrase, by any method. It may consist of a group of letters or words taken from the full version of the word or phrase; for example, the word ''abbrevia ...

(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 back in 2002,

Asturias Asturias (, ; ast, Asturies ), officially the Principality of Asturias ( es, Principado de Asturias; ast, Principáu d'Asturies; Galician-Asturian: ''Principao d'Asturias''), is an autonomous community in northwest Spain. It is coextensiv ...

Spain , image_flag = Bandera de España.svg , image_coat = Escudo de España (mazonado).svg , national_motto = ''Plus ultra'' (Latin)(English: "Further Beyond") , national_anthem = (English: "Royal March") , i ...

, as well as in caves in Spanish

Cantabria Cantabria (, also , , Cantabrian: ) is an autonomous community in northern Spain with Santander as its capital city. It is called a ''comunidad histórica'', a historic community, in its current Statute of Autonomy. It is bordered on the east ...

and in caves in

France France (), officially the French Republic ( ), is a country primarily located in Western Europe. It also comprises of overseas regions and territories in the Americas and the Atlantic, Pacific and Indian Oceans. Its metropolitan area ...

and

Portugal Portugal, officially the Portuguese Republic ( pt, República Portuguesa, links=yes ), is a country whose mainland is located on the Iberian Peninsula of Southwestern Europe, and whose territory also includes the Atlantic archipelagos of ...

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

etiological Etiology (pronounced ; alternatively: aetiology or ætiology) is the study of causation or origination. The word is derived from the Greek (''aitiología'') "giving a reason for" (, ''aitía'', "cause"); and ('' -logía''). More completely, e ...

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 ( el, πάθος, "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 ...

ic for certain bats.

Necropsies An autopsy (post-mortem examination, obduction, necropsy, or autopsia cadaverum) is a surgical procedure that consists of a thorough examination of a corpse by dissection to determine the cause, mode, and manner of death or to evaluate any di ...

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 phenomena a ...

pathology Pathology is the study of the causes and effects of disease or injury. 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 ...

, 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 be ...

examination suggested

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

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

tourists Tourism is travel for pleasure or business; also the theory and practice of touring, the business of attracting, accommodating, and entertaining tourists, and the business of operating tours. The World Tourism Organization defines tourism mo ...

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 re ...

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 ( hu, Magyarország ) is a landlocked country in Central Europe. Spanning 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 ...

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. Using nanopore sequencing, a single molecule of DNA or RNA can be sequenced without the ne ...

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

Marburg Marburg ( or ) is a university town in the German federal state (''Bundesland'') of Hesse, capital of the Marburg-Biedenkopf district (''Landkreis''). The town area spreads along the valley of the river Lahn and has a population of approxima ...

and Ravn viruses ever isolated from bats.

Virology

Genome

Although LLOV was isolated in

tissue culture Tissue culture is the growth of tissues or 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-solid, or solid growth medium, su ...

, 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

genome In the fields of molecular biology and genetics, 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 g ...

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 A covalent bond is a chemical bond that involves the sharing of electrons to form electron pairs between atoms. These electron pairs are known as shared pairs or bonding pairs. The stable balance of attractive and repulsive forces between atom ...

linked to a

protein 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, res ...

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

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

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 virological taxon included in the family '' Filoviridae'' (filament-shaped viruses), order ''Mononegavirales''. The members of this genus are called ebolaviruses, and encode their genome in the for ...

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 primate ...

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.

Structure

The structure of LLOV virions has not yet been described. Like all other filoviruses, LLOV virions are expected to be filamentous particles that may appear in the shape of a shepherd's crook or in the shape of a "U" or a "6", and they may be coiled, toroid, or branched. Their diameter is expected to be 80 nm in

width Length is a measure of distance. In the International System of Quantities, length is a quantity with dimension distance. In most systems of measurement a base unit for length is chosen, from which all other units are derived. In the Intern ...

, but vary in length. The LLOV genome suggests that LLOV particles consist of seven structural proteins. At the center would be the

helical Helical may refer to: * Helix, the mathematical concept for the shape * Helical engine, a proposed spacecraft propulsion drive * Helical spring, a coilspring * Helical plc, a British property company, once a maker of steel bar stock * Helicoil A t ...

ribonucleocapsid 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 ...

, which would consist of the genomic RNA wrapped around a

polymer A polymer (; Greek '' poly-'', "many" + ''-mer'', "part") is a substance or material consisting of very large molecules called macromolecules, composed of many repeating subunits. Due to their broad spectrum of properties, both synthetic a ...

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 int ...

s (NP). Associated with the ribonucleoprotein would be the RNA-dependent RNA polymerase (L) with the polymerase cofactor (VP35) and a transcription activator (VP30). The ribonucleoprotein would be embedded in a matrix, formed by the major (VP40) and minor (VP24) matrix proteins. These particles would be surrounded by a

lipid membrane The lipid bilayer (or phospholipid bilayer) is a thin polar membrane made of two layers of lipid molecules. These membranes are flat sheets that form a continuous barrier around all cells. The cell membranes of almost all organisms and many vir ...

derived from the host cell membrane. The membrane would anchor a glycoprotein (GP_1,2) that projects 7 to 10 nm spikes away from its surface. While nearly identical to ebolavirions and marburgvirions in structure, lloviuvirions may be

antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune respons ...

ically distinct from both (just as they are from each other).

Replication

The LLOV

life cycle Life cycle, life-cycle, or lifecycle may refer to: Science and academia *Biological life cycle, the sequence of life stages that an organism undergoes from birth to reproduction ending with the production of the offspring * Life-cycle hypothesis ...

is hypothesized to begin with virion attachment to specific cell-surface

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

, followed by internalization,

fusion Fusion, or synthesis, is the process of combining two or more distinct entities into a new whole. Fusion may also refer to: Science and technology Physics *Nuclear fusion, multiple atomic nuclei combining to form one or more different atomic nucl ...

of the virion envelope with endosomal membranes and the concomitant release of the virus nucleocapsid 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 di ...

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

NPC1 Niemann-Pick disease, type C1 (NPC1) is a disease of 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 identi ...

). The virus RdRp would partially uncoat the nucleocapsid and

transcribe Transcription refers to the process of converting sounds (voice, music etc.) into letters or musical notes, or producing a copy of something in another medium, including: Genetics * Transcription (biology), the copying of DNA into RNA, the fir ...

the genes 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 synthesizing a protein. mRNA is created during the ...

s, which would then be

translated Translation is the communication of the meaning of a source-language text by means of an equivalent target-language text. The English language draws a terminological distinction (which does not exist in every language) between ''transla ...

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

, 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 (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...

. Virions would

bud In botany, a bud is an undeveloped or embryonic shoot and normally occurs in the axil of a leaf or at the tip of a stem. Once formed, a bud may remain for some time in a dormant condition, or it may form a shoot immediately. Buds may be spec ...

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 weapons Hemorrhagic fevers Tropical diseases Viral diseases Virus-related cutaneous conditions Filoviridae Zoonoses Animal viral diseases