Abbreviations : Report Help
Bernard Delmas, Houssam Attoui, Souvik Ghosh, Yashpal S. Malik, Egbert Mundt and Vikram N. Vakharia
Edited by Jens H. Kuhn and Stuart G. Siddell
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:
Delmas, B., Attoui, H., Ghosh, S., Malik, Y.S., Mundt, E., Vakharia, V.N., and ICTV Report Consortium. 2019, ICTV Virus Taxonomy Profile: Picobirnaviridae, Journal of General Virology, 100, 133–134.
Picobirnaviridae is a family of viruses with bisegmented (rarely unsegmented) dsRNA genomes comprising about 4.1–4.6 kbp in total, with small non-enveloped spherical virions (Table 1.Picobirnaviridae). The family includes one genus (Picobirnavirus) grouping three genetic clusters with high sequence variability, two defined by viruses infecting vertebrates, and a third with viruses found in invertebrates.
Table 1.Picobirnaviridae. Characteristics of the family Picobirnaviridae.
human picobirnavirus, Hy005102 (RNA1: AB186897;RNA2: AB186898), species Human picobirnavirus, genus Picobirnavirus
Non-enveloped, spherical virion, 33–37 nm in diameter
Two double-stranded RNA segments, of 1.7–1.9 kbp and 2.4–2.7 kbp
Not known due to lack of infection models in cell culture or animals
Vertebrates and invertebrates
Virus particles are non-enveloped, spherical, 33–37 nm in diameter, with a capsid layer surrounding the genomic dsRNA segments (Pereira et al., 1988). Owing to the absence of a cell culture system for propagating picobirnaviruses, knowledge of virion protein composition comes from virion-like particles produced by recombinant expression of the gene encoding the capsid protein precursor. The virus-like particles have a triacontahedral (30-sided) organization made of 60 symmetric capsid protein (CP) dimers (Duquerroy et al., 2009). The structure reveals an intricate interface with the N-terminal residues exchanged between the two subunits of the dimer. Two domains can be recognized in CP, namely a shell domain and a projection domain that forms the protrusions that stand out in the three-dimensional reconstruction (Figure 1.Picobirnaviridae).
Virion buoyant density in CsCl is 1.38 to 1.40 g cm-3.
Virions contain two unrelated, linear dsRNA segments (dsRNA1 and dsRNA2) (Pereira et al., 1988). The larger segment (dsRNA1) is 2.4–2.7 kbp with two or three ORFs (Green et al., 1999, Rosen et al., 2000, Wakuda et al., 2005). The smaller segment (dsRNA2) is 1.7–1.9 kbp and is monocistronic. It encodes the viral RNA-dependent RNA polymerase (RdRP). Several picobirnavirus genomes belonging to different genetic clusters are unsegmented with dsRNA2 fused to the 3′-end of dsRNA1 (Li et al., 2015, Shi et al., 2016).
Proteolytic maturation of the capsid protein precursor generates an N-terminal peptide rich in basic residues as well as the mature CP (Duquerroy et al., 2009). An additional protein containing repeats of the ExxRxNxxxE motif is translated from dsRNA1 (Duquerroy et al., 2009, Da Costa et al., 2011). The RdRP is translated from dsRNA2 (Collier et al., 2016).
About twenty complete genomic sequences of vertebrate picobirnaviruses and seven from invertebrate picobirnaviruses are available in sequence databases (see Table 2). Most of these isolates have bipartite genomes. The smaller segment (dsRNA2; 1.7–1.9 kbp) encodes an RdRP, whereas the larger (dsRNA1, 2.4–2.7 kbp) possesses two large open reading frames (ORF) that can be preceded by a small ORF (Wakuda et al., 2005, Woo et al., 2012, Bodewes et al., 2013). The dsRNA1 of human picobirnavirus Hy005102, an isolate of the species Human picobirnavirus, has two large ORFs of 224 (ORF2) and 552 (ORF3) codons, preceded by a shorter one (ORF1) of 39 codons (Figure 2.Picobirnaviridae). The three ORFs overlap by eight (ORF1-ORF2 junction) and one (ORF2-ORF3 junction) nucleotides (nt) (Wakuda et al., 2005). The functionality of ORF1 is unclear and ORF2 encodes a protein of unknown function, but ORF3 encodes a precursor of CP which is auto-catalytically cleaved at about 50–70 residues from its N-terminus to generate a positively-charged peptide and mature CP (illustrated for rabbit picornavirus in Figure 3.Picobirnaviridae); (Duquerroy et al., 2009). dsRNA2 encodes a RdRP with a core component containing the canonical A–B–C motif arrangement of the palm subdomain present in conventional nucleic acid polymerases (Collier et al., 2016).
The 5′- (GUAAA) and 3′- (ACUGC) terminal nucleotide sequences appear to be conserved in genomic dsRNA2 of picobirnaviruses from various hosts (Wakuda et al., 2005, Ghosh et al., 2009, Malik et al., 2014, Navarro et al., 2017). The consensus bacterial ribosomal binding site sequence (AGGAGG) is present in most of the 5′-untranslated region of picobirnavirus genomes (Krishnamurthy and Wang 2018). Poly-A tract and polyadenylation signal are generally not found in the 3′-untranslated region (Wakuda et al., 2005).
Unsegmented genomes resulting from a fusion of the genomic dsRNA2 at the 3′-end of dsRNA1 (the RdRP gene being located in the 3′-moieties) have been described in vertebrate picobirnaviruses (four isolates from Himalayan marmots [Marmota himalayana], one from horses [Equus caballus], and one from goldsaddle goatfish [Parupeneus cyclostomus]) and invertebrate picobirnaviruses (four isolates from diatom colonies) (Li et al., 2015, Shi et al., 2016, Shi et al., 2018). The RNA-dependent RNA polymerase is active with single strand RNA and double-stranded RNA templates and transcription proceeds in a semi-conservative manner. The RNA-dependent RNA polymerase cannot be incorporated into recombinant capsid in the absence of the viral genome (Collier et al., 2016).
Picobirnaviruses are widely distributed geographically among humans and mammals in general, and have also been reported in birds and reptiles (Bodewes et al., 2013, Chandra 1997, Fregolente et al., 2009). They have been mainly identified from fecal specimens and in raw sewage samples (Ludert et al., 1991). Picobirnaviruses have also been identified in invertebrates (Shi et al., 2016).
The pathogenicity of picobirnaviruses has not been established. Studies conducted with immunocompromised persons suggest that they are opportunistic pathogens that may cause diarrhea (Grohmann et al., 1993, Giordano et al., 1998, van Leeuwen et al., 2010). Picobirnaviruses have been detected in stool samples from children with diarrhea and in immunocompromised patients, and they have also been detected in individuals (and in numerous mammals and birds) lacking signs of gastroenteritis (Malik et al., 2014, Navarro et al., 2017). In individuals with inflammatory bowel diseases or solid-organ transplants, picobirnaviruses are predictive of the occurrence of severe enteric graft-versus-host disease, and correlate with higher fecal levels of severity markers (Legoff et al., 2017). Picobirnaviruses have also been detected in the healthy human and pig respiratory tract (Smits et al., 2011, Smits et al., 2012) and in the plasma of a sick horse (Li et al., 2015). Picobirnaviruses can persistently infect pigs (Martinez et al., 2010).
Genetic relationships between picobirnaviruses isolated from different hosts suggest cross-species transmission (Smits et al., 2011, Bányai et al., 2008).
Picobirna: from Greek pico, “small”; Latin prefix bi, “two”, signifies the bisegmented nature of the viral genome as well as the presence of dsRNA; and RNA abbreviation of ribonucleic acid, indicating the nature of the genome.
Two virus species are recognized based on their members’ host specificity and the strong sequence divergence of their capsid proteins (originally the only sequence available for a rabbit picornabirnavirus isolate was the dsRNA1 nucleotide sequence). In the future, species demarcation should take in account the apparently wide host specificity amongst viruses infecting mammals, and also integrate the sequence comparison of their complete genomes. Considering the high degree of RdRP and capsid sequences divergence among completely sequenced picobirnaviruses (20 infecting vertebrates and 7 found in invertebrates), each of the picobirnaviruses defined by a completely sequenced genome may eventually be assigned to a separate virus species.
Pairwise alignments of RdRP amino acid sequences of completely sequenced picobirnaviruses reveal the existence of three genogroups with high level of sequence divergence in each of these genogroups. The percentage of amino acid identity in pairwise alignments ranged from 29 to 81% in genogroup 1, 29 to 64% for genogroup 2, and 31 to 58% in genogroup 3, whereas the inter-genogroup amino acid identities (between genogroups 1, 2, and 3) ranged from 18 to 25%. Sequence divergence is even more pronounced when amino acid sequences of capsid proteins are compared by pairwise alignments. However, the grouping of the capsid sequences in genetic clusters is difficult to perform since identity scores are low (between 10 to 22%). To date, a single virus has been defined as representative of each genogroup. Phylogenetic analysis of RdRP (Figure 4.Picobirnaviridae) reveals three genetic clusters, two recognized as infecting vertebrates (genogroups 1 and 2) and a third (genogroup 3) with viruses infecting invertebrates. Picobirnaviruses exhibit a high level of genetic diversity, particularly marked within genogroup 1 (Ghosh et al., 2009). Vertebrate picobirnaviruses encode a protein with repeats of the ExxRxNxxxE motif (Da Costa et al., 2011), in contrast to invertebrate picobirnaviruses. Novel picobirna-like RdRP-encoding genome segments using an alternative mitochondrial genetic code constitute a fourth genogroup (Shi et al., 2016, Yinda et al., 2018). Exceptions to this rule are two strains (accession numbers WGML128211 and AWV66966), both of which use a mitochondrial genetic code, despite their sequences clustering with those of picobirnaviruses that use the standard genetic code.
Partitiviruses and picobirnaviruses exhibit similarities in genome organization and RdRP sequences. There is no similarity between picobirnaviruses and birnaviruses, as assessed from differences in their genome organization, capsid structure, and encoded proteins.
otarine picobirnavirus HKG-PF080915
dsRNA1: JQ776551; dsRNA2: JQ776552
otarine picobirnavirus PF080902
dsRNA1: KU729754; dsRNA2: KU729755
otarine picobirnavirus PF090307
dsRNA1: KU729753; dsRNA2: KU729767
roe deer picobirnavirus SLO/D38-14/2014
dsRNA1: MG190028; dsRNA2: MG190029
marmot picobirnavirus HT4*
marmot picobirnavirus HT1*
marmot picobirnavirus HT2*
marmot picobirnavirus HT3*
mouse picobirnavirus 504
dsRNA1: LC110352; dsRNA2: LC110353
human picobirnavirus CDC23
dsRNA1: KJ663813; dsRNA2: KJ663814
human picobirnavirus CDC16
dsRNA1: KJ663815; dsRNA2: KJ663816
human picobirnavirus VS6600008
dsRNA1: KJ206568; dsRNA2: KJ206569
fox picobirnavirus Fox5
dsRNA1: KC692367; dsRNA2: KC692366
porcine picobirnavirus 221/04-16/ITA/2004
dsRNA1: KF861768; dsRNA2: KF861773
equine picobirnavirus Equ1
dsRNA1: KR902504; dsRNA2: KR902503
equine picobirnavirus Equ2
dsRNA1: KR902506; dsRNA2: KR902505
equine picobirnavirus Equ3
dsRNA1: KR902508; dsRNA2: KR902507
equine picobirnavirus Equ4*
Beihai goldsaddle goatfish picobirnavirus*
Shāhé picobirna-like virus 1*
Shāhé picobirna-like virus 2*
Běihǎi picobirna-like virus 7**
dsRNA1: KX884063; dsRNA2: KX884062
Běihǎi picobirna-like virus 8
dsRNA1: KX884065; dsRNA2: KX884064
Běihǎi picobirna-like virus 12*
Běihǎi picobirna-like virus 13*
diatom colony-associated dsRNA virus 1
dsRNA1: AP014890; dsRNA2: AP014891
Since only one genus (Picobirnavirus) is currently recognized in the family Picobirnaviridae, the family description above corresponds to the genus description. For clarity, the additional information that can be found on the genus page is also presented below.
Support for preparation of the Online Report and Report Summaries has been provided by: