Peribunyaviridae


Peribunyaviridae

Holly R. Hughes, Scott Adkins, Sergey Alkhovskiy, Martin Beer, Carol Blair, Charles H. Calisher, Mike Drebot, Amy J. Lambert, William Marciel de Souza, Marco Marklewitz, Márcio R. T. Nunes, and Xiǎohóng Shí (石晓宏)

Chapter contents

Posted November 2019

Peribunyaviridae: The family

Member taxa

Supporting information

Citation

A summary of this ICTV Report chapter has been published as an ICTV Virus Taxonomy Profile article in the Journal of General Virology, and should be cited when referencing this online chapter as follows:

Holly R. Hughes, Scott Adkins, Sergey Alkhovskiy, Martin Beer, Carol Blair, Charles H. Calisher, Mike Drebot, Amy J. Lambert, William Marciel de Souza, Marco Marklewitz, Márcio R. T. Nunes, Xiǎohóng Shí (石晓宏), and the ICTV Report Consortium. 2019, ICTV Virus Taxonomy Profile: PeribunyaviridaeJournal of General Virology, (In Press).

Summary

Peribunyaviruses are enveloped and possess three distinct, single-stranded, negative-sense RNA segments comprising 11.212.5 kb in total. The family Peribunyaviridae includes four genera for globally distributed viruses: Orthobunyavirus, Herbevirus, Pacuvirus, and Shangavirus. Most peribunyaviruses are maintained in vertebrate-arthropod transmission cycles that can include transovarial transmission within arthropods. Others are considered as arthropod-specific viruses that are not capable of infecting vertebrates. Arthropods can be persistently infected. Host and geographic ranges are generally restricted although some peribunyaviruses share common or overlapping ranges. Human infection occurs through blood feeding by a vector arthropod. Infections can result in a diversity of human and veterinary clinical outcomes in a strain-specific manner. Segment reassortment is evident between some peribunyaviruses. Genera are monophyletic based on analysis of the viral L protein and members of a genus share relatively similar genomic organizations and transmission cycles.

Table 1.Peribunyaviridae. General characteristics of the family Peribunyaviridae

Characteristic

Description

Typical member

Bunyamwera virus (BUNV) [S segment: D00353; M segment: M11852; L segment X14383], species Bunyamwera orthobunyavirus, genus Orthobunyavirus.

Virion

Enveloped spherical or pleomorphic virions, 80–120 nm in diameter

Genome

Three single-stranded, negative sense RNA molecules, S, M, and L, each of  about 1 kb, 4 kb, and 6.8 kb, encode the nucleocapsid protein (N; S segment), envelope glycoproteins (Gn and Gc; M segment), and L protein that functions as the RNA-directed RNA polymerase and endonuclease (L; L segment)

Replication

Cytoplasmic; primary transcription is primed by “cap snatching” of host cellular RNAs; ribonucleocapsid is involved in primary transcription and unprimed genomic replication

Translation

Translation takes place on ER bound ribosomes for Gn and Gc and on free ribosomes in the cytoplasm for N and L

Host range

Vertebrates and invertebrates (including mammals, birds, mosquito, culicoid, and psychodid sandflies)

Taxonomy

Phylum Negarnaviricota, subphylum Polyploviricotina, class Ellioviricetes, order Bunyavirales , four genera and 95 species

Virion

The peribunyavirus virion (Figure 1.Peribunyaviridae) is spherical or pleomorphic, 80–120 nm in diameter (Martin et al., 1985, Marklewitz et al., 2013), and has surface glycoprotein projections of 5–18 nm (Elliott 2014) that are embedded in a lipid bilayer envelope that is about 5 nm thick. The envelope is derived from cellular Golgi membranes. Small, medium, and large viral ribonucleocapsids are 2–2.5 nm in diameter, 200–3000 nm in length and have helical symmetry. 

Figure 1.Peribunyaviridae. Peribunyavirus virion structure. (Left) Diagrammatic representation of a peribunyavirus virion in cross-section. The surface spikes comprise two glycoproteins termed Gn and Gc. The three helical nucleocapsids are circular and comprise one each of the unique ssRNA segments (L, large; M, medium; S, small) encapsidated by N protein and associated with the L protein. (Right) Negative-stained transmission electron microscopic of California encephalitis virus virions (image CDC/ Dr. Fred Murphy; Dr. Erskine Palmer).

Physiochemical and physical properties

Information is only available for viruses in the genus Orthobunyavirus. Virions display a density of 1.17–1.19 in sucrose or 1.20 in potassium tartrate; sedimentation coefficient of 350–470S; and a molecular weight of 3–4 × 108 (Bishop et al., 1980).

Proteins

The peribunyavirus virion consists of four structural proteins: two external glycoproteins (Gn and Gc), a nucleocapsid protein (N), and a large protein (L), which possesses RNA-directed RNA polymerase (RdRP) and endonuclease functions (Figure 1.Peribunyaviridae; Table 2.Peribunyaviridae). Non-structural proteins (NSs and NSm) are encoded by some viruses. 

Table 2.Peribunyaviridae. Proteins encoded by peribunyaviruses and their masses (kDa)

Genus

RNA

Encoded protein

Orthobunyavirus

Herbevirus

Pacuvirus

Shangavirus*

L segment

L

259−263

282

259−261

264

M segment

Gn

29−41

35

32

30

Gc

108−120

56

86−88

111.4

NSm

15−18

none

19

27

S segment

N

19−26

25−27

27−28

30

NSs

none or 10−13

none

none

none

*putative protein masses

Nucleic acid

The peribunyavirus genome includes three, negative-sense RNA segments designated S (small), M (medium), and L (large) (Table 3.Peribunyaviridae). The 5′- and 3′-terminal nucleotide sequences of each segment are highly conserved and complementary among viruses of a given genus. Base-pairing of the terminal nucleotides is predicted to form a stable panhandle structure and non-covalently closed circular RNAs (Raju and Kolakofsky 1989) that form individual ribonucleocapsids when complexed with N and L proteins (Figure 1.Peribunyaviridae). Genomic RNAs are not modified on the 5′- or 3′-ends. Viral mRNAs are truncated relative to the vRNA (Marklewitz et al., 2013, Abraham and Pattnaik 1983, Eshita et al., 1985), are not polyadenylated and possess 5′-methylated caps derived from host cellular mRNAs (Patterson et al., 1984).

Table 3.Peribunyaviridae. RNA segments of typical genus members

Genus

Virus

RNA segment (bases)

L

M

S

Orthobunyavirus

Bunyamwera virus

6875

4458

961

Herbevirus

Herbert virus

7428

2684

1090

Pacuvirus

Pacui virus*

6762

4386

741

Shangavirus

Shuāngào insect virus 1*

7008

4620

813

*Open reading frame length

Carbohydrates

Information is only available for viruses in the genus Orthobunyavirus. Virions may contain asparagine-linked mannose sugars on the Gn and Gc proteins. Carbohydrates make up 7% of orthobunyavirus virion weight (Bishop et al., 1980).

Lipids

Information is only available for viruses in the genus Orthobunyavirus. Virion lipids are derived from the host membranes where viruses mature, and include phospholipids, sterols, fatty acids, and glycolipids. Orthobunyavirus virions contain 20–30% lipids by weight (Bishop et al., 1980).

Genome organization and replication

The general genome organization for viruses of each genus is shown in Figure 2.Peribunyaviridae. The S segment encodes the N and, in the case of some orthobunyaviruses, the NSs proteins in an overlapping reading frame. (Marklewitz et al., 2013, de Melo et al., 2018, Mohamed et al., 2009a, Rodrigues et al., 2014). The M segment encodes the Gn and Gc proteins (Fazakerley et al., 1988). Orthobunyaviruses, pacuviruses, and Shuāngào insect virus 1 (the sole member of the genus Shangavirus) also encode an NSm protein between the Gn and Gc proteins ORFs within the polyprotein (Rodrigues et al., 2014, Fazakerley et al., 1988, Li et al., 2015), whereas herbeviruses do not encode NSm (Marklewitz et al., 2013). The L segment encodes the L protein (Endres et al., 1989). 

Figure 2.Peribunyaviridae. Generalized coding strategies of peribunyaviruses. Orthobunyavirus, herbevirus, pacuvirus and shangavirus vcRNAs are depicted in a 3'→5' direction and mRNAs are depicted in a 5'→3' direction. The mRNAs depict ORFs that encode the N, nucleocapsid protein; Gn and Gc, external glycoproteins; L, large protein, as well as the non-structural proteins NSs and NSm. 

Both Gn and Gc proteins are implicated in virion host-cell attachment (Kingsford et al., 1983, Ludwig et al., 1989, Hacker et al., 1995). However, the Gc protein appears to be the primary attachment protein for orthobunyaviruses (Plassmeyer et al., 2005b). Following attachment, the virion enters the cell through clathrin-mediated endocytosis and acidification leads to pH-induced insertion of the viral Gc fusion peptide into the endosomal membranes (Shi and Elliott 2007, Plassmeyer et al., 2005, Jacoby et al., 1993). This insertion facilitates the membrane-to-membrane fusion and subsequent release of ribonucleocapsids into the cytoplasm. Only encapsidated RNA segments serve as templates for both primary transcription and genomic replication (Reguera et al., 2013). Complementary 5′- and 3′-termini are promoters for both mRNA and antigenome synthesis (Kohl et al., 2004). The Gn and Gc proteins, and the NSm protein in the case of some viruses, are translated from a single ORF as a polyprotein precursor which is co-translationally cleaved into mature products by a host signal peptidase (Fazakerley and Ross 1989) and the host intramembrane-cleaving protease, signal peptide peptidase (SPP) (Shi et al., 2016). Gn and Gc proteins are modified by the N-linked glycans (Madoff and Lenard 1982, Shi et al., 2005) and are targeted to, and retained in the Golgi complex (Lappin et al., 1994) where the virion assembles and buds. Virions bud into Golgi cisternae and are transported to the cell surface by the secretory pathway (Salanueva et al., 2003).

Nucleocapsid proteins are abundant in infected cells (Fuller et al., 1983) and encapsidate viral genomic and antigenomic RNA segments, thereby protecting them from degradation. The L protein is responsible for both primary transcription and genomic replication (Elliott and Schmaljohn 2013) and includes a characterized polymerase (RdRP) module shared by other families of negative-sense RNA viruses (Walter and Barr 2011). The L protein N-terminal domain possesses endonuclease activity that cleaves capped oligonucleotides from the 5′-end of host mRNA. This phenomenon is known as “cap snatching”. Subsequently, this host sequence “cap” primes viral mRNA synthesis (Reguera et al., 2010). NSs protein functions have been characterized in orthobunyaviruses as contributing to the shutdown of mammalian, but not mosquito, host cell protein synthesis (Weber et al., 2001, Thomas et al., 2004, Hart et al., 2009). Orthobunyavirus NSs protein has well documented anti-IFN activity in mammalian systems (Blakqori et al., 2007, Weber et al., 2002). As such, NSs is thought to have a role in potentiating the zoonotic capacity of orthobunyaviruses (Hart et al., 2009) by allowing these viruses to overcome the innate immune responses of vertebrate hosts. The Bunyamwera virus NSm protein is a transmembrane protein and targeted to the Golgi complex where budding occurs (Shi et al., 2006), suggesting that NSm may play a role in virion assembly (Fontana et al., 2008). However, NSm may be dispensable for the generation of infectious viral particles (Kraatz et al., 2018, Tilston-Lunel et al., 2015).

Antigenicity

The orthobunyavirus Gn and Gc proteins are responsible for eliciting hemagglutination-inhibiting and neutralizing antibodies (Kingsford et al., 1983). Complement-fixing antibodies are elicited by the nucleocapsid protein.

Biology

The majority of peribunyaviruses replicate in vertebrates and arthropods and are generally cytopathic in their vertebrate, but not invertebrate, hosts. Others are described as arthropod-specific viruses (Marklewitz et al., 2013) that are not able to replicate in vertebrates. Peribunyaviruses are ecologically diverse and have been found on every continent except Antarctica. A broad diversity of arthropod and vertebrate hosts is evident,as is described on individual genus pages Peribunyaviruses are associated with a wide range of clinical outcomes (see Genus Orthobunyavirus), ranging from subclinical to fatal. In natural infections of mammals, peribunyaviruses are often targeted to a particular organ or cell type. Genetic reassortment has been demonstrated for many peribunyaviruses both in vitro and in vivo and reassortment has been associated with outbreaks of human disease (see Genus Orthobunyavirus). 

Genus demarcation criteria

Inclusion in a genus can be defined by:

  • Forming a monophyletic clade with other viruses in the genus using the L protein sequence
  • Encoding NSs (some orthobunyaviruses) or NSm (all except herbeviruses)
  • N-terminal truncation of the Gc proteins by about 480 amino acids (herbeviruses)
  • host range 

Derivation of names

Peribunyaviridae is derived from the Greek περί [perí], meaning around, and the name of the type orthobunyavirus, Bunyamwera virus. 

Phylogenetic relationships 

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

Figure 3.Peribunyaviridae. Phylogenetic analysis of members of the family Peribunyaviridae. The amino acid sequences comprising the L protein of family members were aligned with Clustal W and a neighbor joining tree was produced based on the JTT model using Mega version 7. This phylogenetic tree and corresponding sequence alignment are available to download from the Resources page.

Similarity with other taxa

Viruses of the family Peribunyaviridae are related phylogenetically most closely to those of Fimoviridae and Tospoviridae (Guterres et al., 2017). 

Related, unclassified viruses

Virus name

Accession number

Virus abbreviation

Reference

Akhtuba virus

L: KF601560*;
M: KF601561*;
S: KF601562*

AKTV

 

Fulton virus

L: MK618652*;
M: MK618653*;
S: MK618654*

FULV

(Williams et al., 2019)

Khurdun virus

L: KF981633;
M: KF981634;
S: KF981635#

KHURV

(Li et al., 2015, Al'khovskii et al., 2013)

Lakamha virus

L: MN092355;
M: MN092356;
S: MN092357

LAKV

(Kopp et al., 2019)

largemouth bass bunyavirus

L: MN119734;
M: MN119735;
S: MN119736

LBBV

(Waltzek et al., 2019)

* - partial genome, # - complete coding genome