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S. M Valles, Y Chen, A. E Firth, D. M. A Guérin, Y Hashimoto, S Herrero, J. R de Miranda and E Ryabov
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:
Valles, S.M., Chen, Y., Firth, A.E., Guérin, D.M.A., Hashimoto, Y., Herrero, S., de Miranda, J.R., Ryabov, E., and ICTV Report Consortium. 2017, ICTV Virus Taxonomy Profile: Iflaviridae, Journal of General Virology, 98, 527–528.
Iflaviridae is a family of small non-enveloped viruses with RNA genomes of approximately 9-11 kilobases in length encoding a single polyprotein. All members infect arthropod hosts with the majority infecting insects. Beneficial and pest insects serve as hosts and infections can be symptomless (Nilaparvata lugens honeydew virus 1), cause developmental abnormalities (deformed wing virus, Varroa destructor virus 1, sacbrood virus), behavioural changes (deformed wing virus, Varroa destructor virus 1, slow bee paralysis virus, sacbrood virus) and premature mortality (deformed wing virus, Varroa destructor virus 1, slow bee paralysis virus, infectious flacherie virus, sacbrood virus) (van Oers 2010).
Table 1.Iflaviridae. Characteristics of the family Iflaviridae.
infectious flacherie virus (AB000906), species Infectious flacherie virus, genus Iflavirus
Non-enveloped, 22-30 nm diameter virions
9-11 kb of positive-sense, non-segmented RNA
Cytoplasmic within viral replication complexes formed from a variety of host cellular membranes
Directly from genomic RNA containing an internal ribosomal entry site (IRES)
Member of the order Picornavirales; >10 species in the single genus Iflavirus
Virions are roughly spherical and exhibit icosahedral symmetry with a diameter of 22–30 nm. Virions have no envelope and no distinctive surface structures (Figure 1.Iflaviridae).
Figure 1.Iflaviridae. (Left) Surface view of the virion of infectious flacherie virus along a five-fold axis reconstructed by cryo-electron microscopy. The bar represents 10 nm (courtesy of J. Hong). (Right) Negative contrast electron micrograph of isometric particles of an isolate of infectious flacherie virus. The bar represents 100 nm (courtesy of H. Bando).
Virions have a buoyant density of between 1.29 and 1.38 g ml−1 in CsCl. Deformed wing virus and Varroa destructor virus 1 are unstable in isolation.
Virions contain one molecule of linear, positive-sense, single-stranded RNA approximately 9–11 kilobases in length containing a single large open reading frame (ORF) encoding a polyprotein of approximately 3,000 amino acids. A genome-linked virus protein, VPg, is covalently attached to the 5′ end of the genomic RNA and the 3' terminus is polyadenylated. The untranslated regions (UTRs) flanking both ends of the ORF vary in size according to species.
All proteins arise by proteolytic cleavage of the single polyprotein. Mature virions contain three major structural proteins (VP1, VP2 and VP3) generally between 28 and 44 kDa. The structural proteins are present in the N-terminal region of the polyprotein (Figure 2.Iflaviridae). A fourth smaller capsid protein (VP4) of around 4–12 kDa has been reported in some species and is located in the second position of the capsid precursor coding region. Minor quantities of the uncleaved precursors have been reported for some species. Non-structural proteins involved in replication and polyprotein processing are present in the C-terminal region of the polyprotein. The non-structural proteins include an RNA helicase (Gorbalenya et al., 1988), a 3C-like cysteine protease (Ye et al., 2012), and an RNA-dependent RNA polymerase (Koonin and Dolja 1993), which are found in this order (Figure 2.Iflaviridae). Each of the non-structural proteins exhibits conserved, defining domains (van Oers 2010).
Figure 2.Iflaviridae. Genome structure of infectious flacherie virus. The genome encodes a single polyprotein that is auto-catalytically cleaved into three major structural proteins (VP1, VP2, VP3) and non-structural proteins used in replication. The 5′ end of the genome carries a covalently linked protein, VPg, which plays an important role in RNA replication and the 3′ terminus of the genome is polyadenylated. The structural proteins are encoded in the 5′-proximal region of the genome and the non-structural proteins in the 3′-proximal region. The capsid proteins, arranged in the order VP2-VP4-VP3-VP1, are preceded by a short leader protein (L). The approximate positions of the helicase (Hel), protease (Pro) and RNA-dependent RNA polymerase (RdRp) domains are shown.
Iflaviruses possess single-stranded, positive-sense, non-segmented RNA genomes with a single ORF. The ORF is translated directly into a polyprotein that is subsequently processed to yield structural/capsid (N-terminal region) and non-structural (C-terminal region) proteins. Replication occurs in the host cell cytoplasm. The capsid proteins, arranged in the order of VP2-VP4-VP3-VP1, are often preceded by a short leader protein (L) of unknown function that is removed from VP2 before capsid assembly. VP4 is analogous to VP4 present in some dicistroviruses and in the case of infectious flacherie virus (IFV) is present as a minor structural component of the capsid. The non-structural proteins include an RNA helicase, a 3C-like cysteine protease, and an RNA-dependent RNA polymerase (Figure 2.Iflaviridae). Translation initiation has been reported to be mediated by a 5'UTR IRES in many iflaviruses, which is likely a common mechanism in the genus (Ongus et al., 2006, Lu et al., 2007). The viral RNA is infectious and serves as both genomic and viral mRNA. Mechanisms of polyprotein processing and the effects on host cell macromolecular synthesis during infection have not been well studied for the members of this family.
Honeybee viruses in the genus are serologically distinct from each other. There are no known serological relationships between the other members of the genus.
All member viruses have been isolated from arthropods. The host range of most members has not been examined. However, the honeybee iflaviruses, deformed wing virus, Varroa destructor virus 1, slow bee paralysis virus, and sacbrood virus have been shown to infect other Apis species, as well as several Bombus species. Deformed wing virus and Varroa destructor virus 1 also infect bee-parasitic mites (Varroa and Tropilaelaps spp.). Vertical and sexual transmission has been reported in the honey bee for deformed wing virus and Varroa destructor virus 1. The most common route of infection among the iflaviruses is through ingestion of virus-contaminated food sources. Trophallaxis in social insects facilitates intra-colonial virus dispersal. Deformed wing virus, Varroa destructor virus 1, and slow bee paralysis virus can also be vectored to honeybees by parasitic mites (Varroa and Tropilaelaps genera). In addition to the gut, gonads, fat body, muscle, brain and glandular tissues also have been shown to be a target for several iflaviruses. Once the virus gains entry to the host cell, the infection process is rapid with progeny virus being produced in hours.
Sequence identity at the amino acid level between the capsid proteins of isolates and strains of a species is above 90%.
Ifla: siglum derived from the type species, Infectious flacherie virus.
Phylogenetic analysis of the complete translated genomes of iflaviruses show that a number of distinct clades exist. These will be likely separated taxonomically into different genera in the near future as more virus sequences become available (Figure 3.Iflaviridae). There does not appear to be an obvious host-based evolutionary relationship because each clade is composed of viruses infecting hosts from different insect orders.
Figure 3.Iflaviridae. Mid-point rooted phylogenetic tree. Peptide sequences were aligned with MUSCLE (Edgar 2004), and a Bayesian Markov chain Monte Carlo based phylogenetic tree produced with MrBayes (Ronquist et al., 2012) sampling across the default set of fixed amino acid rate matrices, with 5 million generations, discarding the first 25% as burn-in. Node labels indicate posterior probabilities. Accession numbers and virus names are provided on the tree; viruses belonging to existing Iflavirus species are in blue font while unclassified isolates are in black. This phylogenetic tree and corresponding sequence alignment are available to download from the Resources page.
Family Iflaviridae is a member of the order Picornavirales. Iflaviruses share properties with other members of the order (Dicistroviridae, Marnaviridae, Picornaviridae, and Secoviridae), including three replication proteins (helicase, protease, RNA dependent RNA polymerase), non-enveloped icosahedral virions of approximately 30 nm diameter, presence of a small VPg protein at the 5' terminus, and a polyadenylated 3' terminus.
Bombyx mori iflavirus
Brevicoryne brassicae virus*
Ceratitis capitata iflavirus 1
Ceratitis capitata iflavirus 2
Formica exsecta virus 2
Graminella nigrifrons virus 1
Halyomorpha halys virus
Heliconius erato iflavirus
La Jolla virus
Laodelphax striatella honeydew virus 1
Laodelphax striatellus iflavirus 2
Nilaparvata lugens honeydew virus 2
Nilaparvata lugens honeydew virus 3
Osiphanes invirae iflavirus 1
Thaumetopoea pityocampa iflavirus 1
Since only one genus (Iflavirus) is currently recognized in the family Iflaviridae, 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.
Sequence identity at the amino acid level between the capsid proteins of isolates and strains of a species is above 90%. Note that, by this definition, Laodelphax striatella honeydew virus 1 and Laodelphax striatellus iflavirus 2 (related, unclassified species) are the same species. The Iflaviridae family is expanding rapidly and will likely undergo revision in the near future.
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