Family: Phenuiviridae

 

Takahide Sasaya (笹谷孝英), Gustavo Palacios, Thomas Briese, Francesco Di Serio, Martin H. Groschup, Yutaro Neriya (煉谷裕太朗), Jin-Won Song (송진원), and Yasuhiro Tomitaka (冨髙保弘)

The citation for this ICTV Report chapter is the summary to be published as Sasaya et al., (2023):

ICTV Virus Taxonomy Profile: Phenuiviridae 2023, Journal of General Virology, (in press)

Corresponding authors: Takahide Sasaya (笹谷孝英) (tsasaya@affrc.go.jp); Gustavo Palacios (gustavo.palacios@mssm.edu
Edited by: Jens H. Kuhn and Stuart G. Siddell 
Posted: September 2023

Summary

The family Phenuiviridae includes 22 genera and 151 species for 172 viruses with segmented negative-sense or ambisense RNA genomes of 8.1–25.1 kb in total (Table 1.Phenuiviridae). Virions are typically enveloped with spherical or pleomorphic morphology, but non-enveloped filamentous virions have also been reported. Individual RNA genome segments have partially complementary termini. Phenuivirid genomes generally have four genes encoding structural proteins (L, Gn, Gc, and N). However, several phenuivirid genomes lack genes for Gn and Gc and many phenuivirid genomes encode additional non-structural proteins, such as a movement protein (MP) that enables cell-to-cell movement in plant hosts and a viral suppressor protein of RNA silencing (VSR) that counteracts plant antiviral defence mechanisms, in additional genes or in alternative open reading frames. The family is ecologically diverse with members infecting livestock animals and humans, birds, crustaceans, plants and fungi. Phenuivirids have also been detected in invertebrates, including arthropods, some of which act as biological vectors for transmission to other animals or plants, or may serve as their unique host. Phenuivirids include important pathogens of humans, livestock, seafoods, and agricultural crops.

Table 1.Phenuiviridae. Characteristics of members of the family Phenuiviridae

CharacteristicDescription
ExampleRift Valley fever virus (RVFV) [S segment: DQ380151; M segment: DQ380206; L segment DQ375403], species Phlebovirus riftense, genus Phlebovirus
VirionEnveloped spherical or pleomorphic virions, 80–120 nm in diameter comprised of a helical nucleocapsid surrounded by a lipid bilayer envelope. Some phenuivirids produce non-enveloped filamentous virions, 2–2.5 nm in diameter, 200–3000 nm in length
Genome8.1–25.1 kb in total, comprising 2–8 segments of negative-sense or ambisense RNA, of 0.8–9.8 kb
ReplicationCytoplasmic. The nucleocapsid protein (N) encapsidates the genomic RNA forming ribonucleoprotein (RNP) complexes with large protein (L) containing the viral RNA-directed RNA polymerase (RdRP). Anti-genomic RNAs are generated and serve as templates for synthesis of nascent RNP complexes containing genomic RNA.
TranslationFrom capped mRNAs that lack poly(A) termini. The 5′-cap structure is derived from cellular mRNAs via cap-snatching
Host rangeVertebrates, including mammals and birds, invertebrates, plants, and fungi
TaxonomyRealm Riboviria, kingdom Orthornavirae, phylum Negarnaviricota, class Ellioviricetes, order Bunyavirales: 22 genera and 151 species

Genus Bandavirus. Viruses assigned to this genus infect mammals, including humans, and are transmitted by ticks in which they replicate and propagate by transovarian transmission. Several bandaviruses cause fever and signs of central nervous system involvement in young ruminants and/or have been associated with fatal thrombocytopenia fever syndrome in humans. Virus particles are spherical or pleomorphic and have surface glycoprotein projections which are embedded in a lipid bilayer envelope. Genomes consist of three segments containing four canonical phenuivirid structural protein genes encoding L, Gn, Gc, and N, and one non-structural protein gene (NSs).

Genus Beidivirus. The single virus assigned to this genus was found by high-throughput sequencing of RNA from a pool of flies from China. The genome consists of three segments and contains the canonical phenuivirid structural protein genes encoding L, Gn, Gc, and N.

Genus Citricivirus. The single virus assigned to this genus was found by high-throughput sequencing of RNA from a brown citrus aphid pool from China. The genome consists of three segments and contains the canonical phenuivirid structural protein genes encoding L, Gn, Gc, and N.

Genus Coguvirus. Viruses assigned to this genus infect a wide range of dicotyledon plants and are transmitted by grafting. Virus particles are flexuous filaments and do not have envelopes. Genomes consist of two or three segments with two structural protein genes encoding L and N, and one non-structural protein gene likely encoding a cell-to-cell movement protein (MP) that enables cell-to-cell movement in plant hosts.

Genus Entovirus. The single virus assigned to this genus was found by high-throughput sequencing of RNA from entoleucan fungi obtained from the rhizosphere of avocados in Spain. The genome consists of two segments with two structural protein genes encoding L and N, and one non-structural protein gene likely encoding MP.

Genus Goukovirus. Viruses assigned to this genus have been isolated from, or detected in, mosquitoes and aphids. Goukoviruses replicate in insects but not in vertebrate cells. Virus particles are spherical or pleomorphic and have surface glycoprotein projections which are embedded in a lipid bilayer envelope. Genomes consist of three segments containing four canonical phenuivirid structural protein genes encoding L, Gn, Gc, and N.

Genus Horwuvirus. Viruses assigned to this genus have been detected by high-throughput sequencing of RNA from fire ants, horseflies, and mosquitoes. Genomes consist of four segments and contain four canonical phenuivirid structural protein genes encoding L, Gn, Gc, and N, and one non-structural protein gene of unknown function.

Genus Hudivirus. The single virus assigned to this genus was found by high-throughput sequencing of RNA from a fly pool from China. The genome consists of three segments and contains four canonical phenuivirid structural protein genes encoding L, Gn, Gc, and N.

Genus Hudovirus. The single virus assigned to this genus was found by high-throughput sequencing of RNA from a butterfly pool from China. The genome consists of three segments and contains four canonical phenuivirid structural protein genes encoding L, Gn, Gc, and N.

Genus Ixovirus. Viruses assigned to this genus have been detected in RNA from ticks. Genomes consist of two segments and contain only two structural protein genes encoding L and N. Vertebrate hosts have not been identified.

Genus Laulavirus. Viruses assigned to this genus have been found in RNA from fungi and ticks. Genomes consist of three segments containing two structural protein genes encoding L and N, and one non-structural protein gene probably associated with the MP of plant viruses.

Genus Lentinvirus. The single virus assigned to this genus was found by high-throughput sequencing of RNA from shiitake from Japan. The genome consists of two segments containing two structural protein genes encoding L and N, and one non-structural protein gene likely encoding MP.

Genus Mechlorovirus. The single virus assigned to this genus was detected in a melon plant showing chlorotic spots and yellowing of the older leaves. Virus particles are filamentous and flexuous and do not have envelopes. This virus has the most complex genome organization known among phenuivirids, with eight segments containing thirteen genes encoding L, N, and eleven non-structural proteins of unknown function.

Genus Mobuvirus. Viruses assigned to this genus have been found by high-throughput sequencing of RNA from fleas, moths and mosquitoes. Genomes consist of three segments and contain the canonical phenuivirid structural protein genes encoding L, glycoprotein precursor, and N. Mobuviruses of moths encode an additional non-structural protein of unknown function.

Genus Phasivirus. Viruses assigned to this genus have been isolated from flies and mosquitoes. Phasiviruses replicate in insects but not in vertebrate cells. Virus particles are spherical or pleomorphic and have surface glycoprotein projections which are embedded in a lipid bilayer envelope. Genomes consist of three segments containing four canonical phenuivirid structural protein genes encoding L, Gn, Gc, and N.

Genus Phlebovirus. Viruses assigned to this genus infect mammals, including humans, and are transmitted by mosquitoes, phlebotomine sandflies and ticks in which they replicate and propagate by transovarian transmission. Several phleboviruses cause abortion and often manifest as congenital malformations in livestock and/or have been associated with fatal febrile illness and occasionally encephalitides in humans. Virus particles are spherical or pleomorphic and have surface glycoprotein projections which are embedded in lipid bilayer envelopes. Genomes consist of three segments containing four canonical phenuivirid structural protein genes encoding L, Gn, Gc, and N, and two non-structural protein genes encoding NSm and NSs.

Genus Pidchovirus. Viruses assigned to this genus have been found by high-throughput sequencing of RNA from beetles and moths. Genomes consist of three segments containing four canonical phenuivirid structural protein genes encoding L, Gn, Gc, and N.

Genus Rubodvirus. Viruses assigned to this genus have been found in apples and grapevines and are transmitted by grafting. Genomes consist of three segments containing two structural protein genes encoding L and N, and one non-structural protein gene likely encoding MP.

Genus Tanzavirus. The single virus assigned to date to this genus has been detected by high-throughput sequencing of a plasma sample from a human in Tanzania with a history of fever, headache and back pain. The genome consists of three segments containing four canonical phenuivirid structural protein genes encoding L, Gn, Gc, and N.

Genus Tenuivirus. Viruses assigned to this genus infect a wide range of monocotyledon plants and are transmitted by planthoppers or leafhoppers in which they replicate and propagate by transovarian transmission. Virus particles are flexuous filaments and do not have envelopes. Several tenuiviruses cause serious problems in rice and maize production. Genomes have a relatively complex organization among phenuivirids with up to six segments and up to twelve genes encoding L, N, and five to ten non-structural proteins including MP, a viral suppressor of RNA silencing (VSR) that counteracts plant antiviral defence mechanisms, and a major non-capsid protein (NCP) that forms characteristic inclusion bodies in infected plant and/or vector insect cells.

Genus Uukuvirus. Viruses assigned to this genus infect birds and mammals, including humans, and are transmitted by ticks in which they replicate and propagate by transovarian transmission. Uukuviruses have not been considered to be of public health or agricultural significance, although antibodies to some uukuviruses have been detected in sera from humans, cattle, birds, and wild animals. Virus particles are spherical or pleomorphic and have surface glycoprotein projections that are embedded in lipid bilayer envelopes. Genomes consist of three segments containing four canonical phenuivirid structural protein genes encoding L, Gn, Gc, and N, and one non-structural protein gene encoding NSs.

Genus Wenrivirus. The single virus assigned to this genus infects prawns and shrimps. The viral infection increases the mortality of the prawns and shrimps. The genome consists of four segments containing four structural protein genes encoding L, Gn, Gc, and N, and one non-structural protein gene of unknown function.

Virion

Morphology

Phenuivirids that produce enveloped particles mainly infect vertebrates and invertebrates. By contrast, phenuivirids that produce nonenveloped particles mainly infect plants and fungi, as well as their arthropod vectors. Enveloped particles are spherical or pleomorphic, 80–120 nm in diameter, and have surface glycoprotein projections of 5–10 nm that are embedded in lipid bilayer envelopes approximately 5 nm thick (Figure 1.Phenuiviridae). Envelopes are usually derived from cellular Golgi membranes, or on occasion, from cell-surface membranes. Nonenveloped filamentous particles are spiral-shaped, branched or like a panhandle, 2–2.5 nm in diameter, with lengths proportional to the lengths (200–3000 nm) of the segmented genomic RNAs (Figure 1.Phenuiviridae).

Phenuiviridae virion
Figure 1.Phenuivridae. (Left) Diagrammatic representation of an enveloped phenuivirid virion in cross-section. The surface spikes comprise two glycoproteins termed Gn and Gc (previously referred to as G1 and G2). The three helical nucleocapsids are panhandled in shape and comprise one each of the negative-sense RNA segments (L segment or RNA1, large or first; M segment or RNA2, medium or second; S segment or RNA3, small or third) encapsidated by N protein and associated with the L protein. (Middle) Cryo-electron micrograph of purified uukuvirus particles (Uukuniemi virus). The bar represents 100 nm (courtesy of C-H von Bornsdorff). (Right) Electron micrograph of purified tenuivirus particles (rice hoja blanca virus). The bar represents 100 nm (Courtesy of A.M. Espinoza).

Physicochemical and physical properties

The relative molecular mass (Mr) of enveloped virions is 300×106 to 400×106 with an S20, W of 350–500. Virion buoyant densities in sucrose and CsCl are 1.16–1.18 and 1.20–1.21 g cm−3, respectively. Virions are sensitive to heat, lipid solvents, detergents, and formaldehyde. Non-enveloped virions are separated into four or five components by sucrose density gradient centrifugation, but form one component with a buoyant density 1.282–1.288 g cm−3 when centrifuged to equilibrium in CsCl solutions (Gingery et al., 1981, Hibino et al., 1985a, Ishikawa et al., 1989).

Nucleic acid

The viral genome comprises two to eight single-stranded molecules of negative-sense or ambisense RNA, which total 8.1–25.1 kb. The terminal nucleotides of each genome RNA segment are base-paired, forming non-covalently closed RNP complexes. The terminal sequences of genome segments are conserved among viruses of each genus but are different from those of viruses of other genera (Table 2.Phenuiviridae). The genomic RNAs are not modified at their 5′-termini. The Mr of the genome ranges from 4.8×106–8×106 and this constitutes 1–2% of the virion by weight. Viral mRNAs are not polyadenylated and are truncated relative to the genomic RNAs at their 3′-termini. The mRNAs have 5′-methylated caps and 10–18 non-templated nucleotides at their 5′-termini derived from host-cell mRNAs.

Table 2.Phenuiviridae. RNA segments of typical genus members

Genus

Virus

RNA segments

Conserved reverse complementary termini

 

 

 

Number of segments

Number of bases

 

 

 

 

 

 

L or RNA1

M or RNA2

S or RNA3 (RNA2)*

S2 or RNA4

3′

5′

 

Bandavirus

severe fever with thrombocytopenia syndrome virus

3

6368

3378

1744

none

ACACAGAGAC….

….GUCUUUGUGU

 

Beidivirus

Húběi diptera virus 3

3

6742

3763

1591

none

ND

ND

 

Citricivirus

Aphis citricidus bunyavirus

3

7037

3462

1163

none

ND

ND

 

Coguvirus

citrus concave gum- associated virus

2

6681

none

2703

none

ACACAAAGAU….

….AUCUAUGUGU

 

Entovirus

Entoleuca phenui-like virus 1

2

7256

2816

none

none

ACACAAAGAC….

….GUCUUUGUGU

 

Goukovirus

Gouléako virus

3

6358

3188

1087

none

ACACAGUGAC….

….GACUUUGUGU

 

Horwuvirus

Wǔhàn horsefly virus

4

9549

2804

1889

1698

ND

ND

 

Hudivirus

Húběi diptera virus 4

3

6947

4186

1236

none

ND

ND

 

Hudovirus

Húběi lepidoptera virus 1

3

7545

5114

1254

none

ACACAAAGAC….

….GUCUUUGUGU

 

Ixovirus

blacklegged tick virus 1

2

6733

2468

none

none

ACACAAAGGC….

….GCCAUUGUGU

 

Laulavirus

Laurel Lake virus

3

7253

2506

1142

none

ACACAAAGUC….

….GUCUUUGUGU

 

Lentinuvirus

Lentinula edodes negative-strand RNA virus 2

2

7082

none

2754

none

ACACAAAGAC….

….GUCUUUGUGU

 

Mechlorovirus

melon chlorotic spot virus

8

9096

1,847

1598

1,592

ACACAAAGUC….

….GACUUUGUGU

 

Mobuvirus

Mothra virus

3

6976

1,967

1520

none

ND

ND

 

Phasivirus

Badu virus

3

6863

3871

1513

none

ACACAAAGAC….

….GUCUUUGUGU

 

Phlebovirus

Rift Valley fever virus

3

6404

3885

1690

none

ACACAAAGAC….

….GUCUUUGUGU

 

Pidchovirus

Pidgey virus

3

6914

3850

1010

none

ND

ND

 

Rubodvirus

apple rubbery wood virus 1

3

7219

1613

1303

none

ACCCCUCCAA….

….UGGAGGGGGU

 

Tanzavirus

Dar es Salaam virus

3

6474

3776

1309

none

ND

ND

 

Tenuivirus

rice stripe virus

4

8970

3514

2504

2,157

ACACAAAGUC….

….GACUUUGUGU

 

Uukuivirus

Uukuniemi virus

3

6423

3229

1720

none

ACACAAAGAC….

….GUCUUUGUGU

 

Wenrivirus

Mourilyan virus

4

6319

2990

1557

1364

ACACAAAGAC….

….GUCUUUGUGU

 

* RNA2 in the case of two segementedviruses, i. e. coguviruses, an entovirus, ixoviruses, and a lentinuvirus

ND – not determined

Proteins

Most phenuivirids encode four structural proteins, a large protein (L) encoded by the L segment or RNA1, two external glycoproteins (Gn and Gc) (not encoded by all members) encoded by the M segment, and a nucleocapsid protein (N) encoded by the S segment or RNA3 (RNA2). Additionally, non-structural proteins are expressed from the M segment or RNA2 of members of the genera Coguvirus, Entovirus, Laulavirus, Lentinuvirus, Mechlorovirus, Phlebovirus, Rubodvirus and Tenuivirus, from the S segment or RNA3 of members of the genera Bandavirus, Mechlorovirus, Mobuvirus, Phlebovirus, Tenuivirus and Uukuvirus, from the S2 segment or RNA4 of members of the genera Horwuvirus, Tenuivirus and Wenrivirus, from additional fifth or sixth RNAs of members of the genera Tenuivirus and Mechlorovirus, and from the seventh and eighth RNAs of the member of the genus Mechlorovirus (Table 3.Phenuiviridae and Figure 2.Phenuiviridae).

Table 3.Phenuiviridae. Proteins encoded by phenuivirids and their approximate masses (kDa)a

Genus

RNA segments

 

 

L or RNA1

M or RNA2

S or RNA3 (RNA2)a

S2 or RNA4

 

 

RdRP

NSm or NSvc2

Gn

Gc

N

NSs or NSv3

NSs2 or NSvc4

 

Bandavirus

235–237

none

47–64

54–56

27–28

31–36

none

 

Beidivirus

250

none

79

56

33

none

none

 

Citricivirus

253

none

56

57

34

none

none

 

Coguvirus

250–252

none

39–42

45–53

none

 

Entovirus

271

none

39

45

none

 

Goukovirus

238–240

none

53–56

52–54

28–29

none

none

 

Horwuvirus

332–363

none

17–33

52–77

35–52

none

33–41

 

Hudivirus

255

none

84

56

31

none

none

 

Hudovirus

275

none

107

55

31

none

none

 

Ixovirus

250–253

none

44–58

none

none

 

Laulavirus

256–275

77–79

none

28–30

none

none

 

Lentinuvirus

367

none

35

48

none

 

Mechlorovirusc

341

21

43

27

23

33

 

Mobuvirus

256–273

none

64–68

35–48

none or 17

none

 

Phasivirus

251–262

none

72–90

53–56

29–50

none

none

 

Phlebovirus

228–242

none or 14–56

47–79

45–65

16–37

16–39

none

 

Pidchovirus

263–267

none

65–73

55–56

30

none

none

 

Rubodvirus

276–304

44–45

none

32

none

none

 

Tanzavirus

248

none

76

54

28

none

none

 

Tenuivirusd

336–341

32–36

91–109

33–36

22–24

32–33

 

Uukuivirus

240–250

none

none or 54–59

none or 55

27–51

none or 11–35

none

 

Wenrivirus

233

none

48

52

27

none

46

 

a The proteins of the genera Bandavirus, Goukovirus, Phasivirus, Phlebovirus and Tenuivirus have been demonstrated experimentally to be expressed, while others are only predicted.

b RNA2 in the case of two segemented viruses, i. e., members of the genera Coguvirus, Entovirus, Ixovirus and Lentinuvirus.

c Members of the genus Mechlorovirus additionally have four RNA segements and seven proteins with unknown function. The protein of 33 kDa encoded on RNA4 is a nucleocapsid protein (N) and two proteins of 27 kDa and 23 kDa on RNA3 are non-structural proteins with unknown function.

d Some members of the genus Tenuivirus additionally have one or two RNA segments and one or six proteins with unknown function.

Lipids

Enveloped virions contain 20–30% lipids by weight. Lipids are derived from the cellular membranes from which viruses mature and include phopholipids, sterols, fatty acids, and glycolipids. Non-enveloped virions do not contain lipids.

Carbohydrates

Enveloped virions contain 2–7% carbohydrate by weight. Asparagine-linked sugars on the Gn and Gc proteins are largely of the high mannose type when viruses are grown in vertebrate cells. Non-enveloped virions do not contain carbohydrates.

Genome organization and replication

The general genome organization for viruses of each genus is shown in Figure 2.Phenuiviridae. The viral genome is usually comprised of three molecules designated the large segment (L segment or RNA1), the medium segment (M segment or RNA2), and the small segment (S segment or RNA3). Some phenuivirids have up to five additional segments. For almost all phenuivirids, the L segment or RNA1 is a negative-sense RNA and encodes the L protein on the virus-complimentary (vc)RNA. The M segment or RNA2 is a negative-sense RNA and encodes the external Gn and Gc proteins or a non-structural MP (laulaviruses and rubodviruses). Phleboviruses also encode a non-structural protein (NSm) in a pre-glycoprotein coding region which can act as an apoptosis antagonist. In the case of mechloroviruses and tenuiviruses, RNA2 exhibits an ambisense coding strategy. Tenuivirus RNA2 encodes a glycoprotein-like non-structural protein (NSvc2) on the vcRNA and a viral suppressor of RNA silencing (VSR) that counteracts plant antiviral defence mechanisms based on RNA silencing of the vRNA. Mechlorovirus RNA2 also encodes two non-structural protein of unknown function. S segment or RNA3, or RNA2 in the case of two-segmented viruses, i.e., coguviruses, entoviruses, ixoviruses and lentinuviruses, encodes N. In addition, the S segment or RNA3 of coguviruses, bandviruses, mobuviruses, phleboviruses, tenuiviruses and uukuviruses encodes a non-structural protein on the vRNA. The phlebovirus non-structural protein acts as an interferon antagonist. The tenuivirus non-structural protein (NSv3) shows activity of VSR. Horwuviruses, tenuiviruses, and wenriviruses have a fourth RNA, designated as the S2 segment or RNA4. The horwuvirus and wenrivirus S2 segment is a negative-sense RNA and encodes a non-structural protein of unknown function. The tenuivirus RNA4 is an ambisense RNA and encodes two non-structural proteins, the MP of plant viruses and a major non-capsid protein (NCP) that accumulates in large amounts in the cells of infected plants and vector insects and is presumably associated with symptom development of infected plants. The mechlorovirus segments RNA5 to RNA8 are negative-sense or ambisense and encode non-structural proteins of unknown function.

All replication processes of phenuivirids, i.e., cellular attachment, entry into host cells, transportation to endosomes, penetrating the cytosol, transcription, translation, replication, virion assembly and virion release, occur in and from the cytoplasm. Cellular attachment of enveloped phenuivirid particles is mediated by an interaction of viral glycoproteins with host cell receptors and attachment factors. Dendritic cell‐specific intercellular adhesion molecule‐3‐grabbing nonintegrin (DC‐SIGN) and liver‐specific intercellular adhesion molecule‐3‐grabbing nonintegrin (L‐SIGN) have been reported as the host cell receptor and attachment factor, respectively. Following attachment, the virion enters the cell via clathrin-mediated or caveolin‐mediated endocytosis. Phenuivirids are trafficked from the periphery into the centre of the cytosol via endosomes along intracellular microtubules. During trafficking, early endosomes exchange various materials with the outside and become more acidic. The acidification leads to pH-induced insertion of the viral Gc fusion peptide into the endosomal membranes. The fusion of viral envelopes and endosomal membranes releases the viral RNP complexes into the cytoplasm for replication and transcription of the viral genome. Transcription of genome vRNA into mRNA starts with a "cap‐snatching mechanism", in which host mRNAs are cleaved at a position close to the 5′ cap, mediated by the endonuclease domain of the L protein, as is typical for bunyavirals. Different from many other negative‐sense RNA viruses that terminate transcription at short poly (U) stretches, phenuivirid genomes do not contain poly(U) sequences and transcription stops at termination signal sequences in the untranslated regions of the genome RNAs. Consequently, mRNAs are not polyadenylated. Replication of the virus-sense genome RNA into virus-complementary RNA starts at the 3′-end of the viral genomic RNA and the RNA disengages from the N protein while replication progresses. Both ends of the synthesized RNA bind to specific sites of L and are encapsulated with N and form the progeny complementary RNPs that are used as the template to synthesize the progeny viral genomic RNAs. The progeny viral genomic RNP complexes in the cytoplasm are transported into the lipid bilayer membrane of the Golgi apparatus. The translated precursor glycoproteins are cleaved into Gn and Gc. After Gn and Gc are modified by N-linked glycans and form heterodimers at the endoplasmic reticulum, Gn and Gc are targeted to, and retained in the Golgi apparatus, where virions assemble and bud. Virions bud into Golgi cisternae and are transported to the cell surface by the secretory pathway.

Non-enveloped tenuiviruses do not have glycoprotein genes. Their nonstructural NSvc2 proteins encoded on the second vcRNA2 play roles in cellular attachment, entry into host cells, transportation to endosomes, penetrating the cytosol similar to the glycoproteins of enveloped phenuivirids. That is, the protein is cleaved into two proteins, NSvc2-N and NSvc2-C that interact with the viral RNP complexes. The NSvc2-N binds to an unknown receptor of the vector cells, and binding leads to endocytosis followed by entry of the viral RNPs/NSvc2 complexes into endosomes. Under acidic conditions inside the late endosomes of vector cells, NSvc2‐C undergoes a conformational change that triggers cell membrane fusion, which releases viral RNPs/NSvc2‐N complexes into the cytosol. Transcription of genomic vRNA into mRNA starts with a "cap‐snatching mechanism". The mRNAs of tenuiviruses are not polyadenylated and are truncated relative to the vRNA, similar to the phenuivirids with envelopes. In the case of other non-enveloped phenuivirids, viral entry into host cells is presumed to occur through endocytosis of plant or fungal cells via mechanical wounds, but little is known about the mechanisms of virion attachment, host cell entrance, genome assembly and virion release (Hornak et al., 2016, Ferron et al., 2017, Lu et al., 2019, Koch et al., 2021, Kormelink et al., 2021, Xu et al., 2021, Sun et al., 2022).

Phenuiviridae genome organisation
Figure 2.Phenuivridae. Genome organization of members of each genus in the family Phenuiviridae. Coloured boxes depict ORFs that encode N, nucleocapsid protein; Gn and Gc, external glycoproteins; and L, large protein. White boxes depict ORFs that encode MP, non-structural cell-to-cell movement protein; NCP, major non-capsid protein; NSm or NSvc2, non-structural protein on the M segment or RNA2; NSs, non-structural protein on the S segment; and VSR, viral suppressor of RNA silencing.

Biology

Phenuivirids are ecologically diverse, infecting animals including livestock, humans, birds, crustaceans, plants or fungi. Phenuivirids are also found in invertebrates, including arthropods, some of which may serve as unique hosts or may act as biological vectors for transmission to other animals or plants. Phenuivirids include important pathogens of humans, livestock, seafoods and agricultural crops. Phenuivirids are capable of alternately replicating in their vertebrate or plant hosts, and in their arthropod vectors; they are generally are cytolytic for their hosts but cause little or no cytopathogenicity in their arthropod hosts. Different viruses are transmitted by phlebotomine sand-flies, ticks, mosquitoes, plant hoppers or other arthropod vectors. Some viruses have a very narrow host range, especially for arthropod vectors. Transovarial and venereal transmission have been demonstrated for some phenuivirids in their arthropod vectors. In some instances, avian host and/or vector movements may result in virus dissemination. Some viruses cause a reduction in host-cell protein synthesis in vertebrate cells. In natural infections of mammals, viruses are often targeted to a particular organ or cell type. Some viruses induce cell fusion at low pH. Some members have ion-dependent hemagglutinating activity. Genetic reassortment has been demonstrated for certain members both in vitro and in vivo.

Antigenicity

One or both of the envelope glycoproteins have hemagglutinating and neutralizing antigenic properties. Complement-fixing antigenic determinants are principally associated with nucleocapsid protein.

Derivation of names

Bandavirus: from Bhanjanagar, India, where Bhanja virus was first discovered and, bié Mountains, China, where severe fever with thrombocytopenia syndrome virus was first discovered.

Beidivirus: from Húi (湖北省), China, where Húběi diptera virus 3 was discovered and Diptera, the order of the fly host.

Citricivirus: from the host aphid species Toxoptera citricida (Kirkaldy, 1907) in which Aphis citricidus bunyavirus was first discovered.

Coguvirus: from citrus concave gum disease, presumed to be caused by citrus concave gum-associated virus.

Entovirus: from Entoleuca, the genus of the host fungus.

Goukovirus: from Gouléako, Côte d'Ivoire, where goukovirus-positive mosquitoes were obtained.

Horwuvirus: from the host horsefly and hàn (武汉市), China, where Wǔhàn horsefly virus was discovered.

Hudivirus: from běi (湖北省), China, where Húběi diptera virus 4 was discovered and Diptera, the order of the fly host.

Hudovirus: from běi (湖北省), China, where Húběi lepidoptera virus 1 was discovered and Lepidoptera, the order of the butterfly host.

Ixovirus: from the host tick species Ixodes scapularis (Say, 1821) and I. ricinus (Linnaeus, 1758).

Laulavirus: from Laurel Lake, USA, where Laurel Lake virus was discovered.

Lentinuvirus: from Lentinula edodes ((Berk.) Pegler, 1976), the host of Lentinula edodes negative-strand RNA virus 2.

Mechlorovirus: from melon chlorotic spot disease, caused by melon chlorotic spot virus.

Mobuvirus: from Mothra virus and Bunyavirales.

Phasivirus: from Phasi Charoen, Thailand, where phasivirus-positive mosquitoes were obtained.

Phlebovirus: from phlebotomine vectors of sandfly fever group viruses; in turn derived from the Greek φλέψ (phléps) meaning “vein”.

Pidchovirus: from Pidgey virus and Choristoneura rosaceana (Harris, 1841), the host moth.

Rubodvirus: from apple rubbery wood disease, caused presumably by apple rubbery wood viruses 1 and 2.

Tanzavirus: from Tanzania, where Dar es Salaam virus was discovered.

Tenuivirus: from the Latin tenuis, “thin, fine, weak”, describing the virion morphology of viruses in the genus.

Uukuvirus: from Uukuniemi, a former municipality of Finland, where Uukuniemi virus, assigned to the species Uukuniemi uukuvirus was first isolated.

Wenrivirus: from Wēnzhōu shrimp virus 1, a junior synonym of Mourilyan virus.

Genus demarcation criteria

The coding-complete sequences of all genome segments may be sufficient for phenuivirus classification. Demarcation of genera is based upon comprehensive considerations of virus phylogenetic relationships, genome organization and ecology (e.g., host range, pathobiology and transmission patterns, etc.).

Species demarcation criteria

The criteria demarcating species in the genus are:

 Viruses assigned to different species have less than 95% identity in the amino acid sequence of the RdRP

Relationships within the family

Viruses within the same genus form monophyletic clades based upon phylogenetic reconstruction using the L protein sequence (Figure 3.Phenuiviridae).

Phenuiviridae phylogeny
Figure 3.Phenuiviridae Phylogenetic analysis of phenuivirid genera. Phylogenetic reconstruction is based on a MAFFT-alignment of the RdRP amino acid sequences of phenuivirids using E-INS algorithm. The ML phylogenetic tree was inferred using RaxML-NG performing 1,000 bootstrap replicates. Trees were inferred under the WAG substitution model. Tree branches are proportional to genetic distances between sequences and the scale bars at the bottom indicate substitutions per amino acid. The branch including phleboviruses is collapsed for clarity. A figure with this region expanded is shown on the Phlebovirus genus page as Figure 1.Phlebovirus.

Relationships with other taxa

Phenuivirids are closely related to viruses in the bunyaviral families Arenaviridae, Discoviridae, Leishbuviridae, Mypoviridae, Nairoviridae and Wupedeviridae, and more distantly related to viruses in the bunyaviral families Cruliviridae, Fimoviridae, Peribunyaviridae, Phasmaviridae, Tospoviridae and Tulasviridae.

Related, unclassified viruses

Virus nameAccession numberVirus abbreviation
Alternaria tenuissima negative-stranded RNA virus 2L: MK584855; M: BK061363; S: BK061364AtNSRV2
Austropotamobius brown spot virus (=bunya-like brown spot virus)L: MK881590; M: MK881591; S: MK881592AuBSV
Culex bunyavirus 1L: MH188051CuBV1
Fusarium asiaticum mycobunyavirus 1L: MZ969068; M: MZ969069; S: MZ969070FaMBV1
Fusarium poae negative-stranded RNA virus 2L: LC150619FpNSV2
Húběi bunya-like virus 2Seg1: KX884780; Seg2: KX884781HbBLV2
Húběi bunya-like virus 3Seg1: KX884778; Seg2: KX884779HbBLV3
Húběi bunya-like virus 13Seg1: KX884784; Seg2: KX884785HbBLV13
Húběi insect virus 1Seg1: KX884735; Seg2: KX884736HbIV1
lettuce dieback associated virusRNA1: MT386514; RNA2: MT386515; RNA3: MT386516LeDaV
Linepithema humile bunyan-like virus 1L: MH213237; S: MH213238LBLV1
otter fecal phlebovirusM: KF823817*; S: KF823816*OFPV
Pälkäne phenui-like virus 2L: ON955229PaPLV2
salarivirus Mos8CM0L: KX924627*; M: KX924628*; S: KX924629SaVMos8CM0
Sclerotinia sclerotiorum phlebo-like virus 1L: KC601996SsNSRV1
Sclerotinia sclerotiorum negative-stranded RNA virus 5L: KF913892; M: BK061361; S: BK061362SsNSRV5
Shāhé heteroptera virus 3L: KX884813; M: KX884814; S: KX884815ShaHV3
Shāyáng bunya-like virus 1Seg1: KX884835ShBLV
Shuāngào insect virus 3L: KM817681; M: KM817716; S: KM817742ShIV3
soybean cyst nematode associated rice stripe virusL: HM849041ScTV
soybean cyst nematode associated Uukuniemi virusL: HM849040ScPV
sugar beet cyst nematode virus 2L: KY609505; M: MH282849*SBCNV2
Timbillica virusL: MK026589; S: MK026590*TimV
Vietnamese bat bunyavirus- Bat/VNM/16715_13L: KX886759; S: KX886760VBBV16715_13
Wēnlǐng crustacean virus 7Seg1: KX884859; Seg2: KX884860WeCV7
Wǔhàn insect virusL: KM817691; S: KM817752*WuIV
Wǔhàn insect virus 16Seg1: KX884854; Seg2: KX884855WuIV16
Xīnzhōu bunya-like virus 1Seg1: KX884868XBLV1
Zhee mosquito virusL: KM817705ZhMV

* Sequences do not comprise the complete genome segment.

Virus names and virus abbreviations are not official ICTV designations.