|Group:||Group II (ssDNA)|
Parvoviridae is a family of viruses. The Parvoviridae family1 includes a large number of small, rugged, genetically-compact DNA viruses known collectively as parvoviruses. There are currently 56 species in this family, divided among 26 genera and two subfamilies.2 Members of this family infect a wide array of hosts and have been divided into two subfamilies, which infect either vertebrates (the Parvovirinae) or invertebrates (Densovirinae).
Parvovirus B19 was the first pathogenic human parvovirus to be discovered and is best known for causing a childhood exanthem called "fifth disease" (erythema infectiosum), although it is also associated with other diseases including arthritis.
Parvovirus particles (virions) have a durable non-enveloped protein capsid ~20–30 nm in diameter that contains a single copy of the linear single-stranded ~ 5kb DNA genome, which terminates in small imperfect palindromes that fold into dynamic hairpin telomeres.345 These terminal hairpins are hallmarks of the family, giving rise to the viral origins of DNA replication and mediating multiple steps in the viral life cycle including genome amplification, packaging, and the establishment of transcription complexes.67 However, they are often refractory to detection by PCR amplification strategies since they tend to induce polymerase strand-switching.8 Many parvoviruses are exceptionally resistant to inactivation, remaining infectious for months or years after release into the environment.910
Viruses in this family have small protein virions that exhibit T=1 icosahedral symmetry. Their capsid shells are assembled from 60 icosahedrally-ordered copies of a single core protein (VP) sequence, but some of these VP proteins also have N-terminal extensions that are not visible in X-ray structures.34567 Biochemical and serological studies indicate that these extensions become successively exposed at the particle surface during virus maturation and cell entry, where they contribute to virion stability and mediate specific steps in cell trafficking. Parvoviruses appear to be unique in encoding a broad spectrum phospholipase A2 (PLA2) activity, typically in the N-terminus of the longest (VP1) subset of their capsid proteins, which is deployed to mediate virion transfer across the lipid bilayer of host cells1112
|Genus||Structure||Symmetry||Capsid||Genomic Arrangement||Genomic Segmentation|
The viral genome is 4–6 kilobases in length and terminates in imperfectly-palindromic hairpin sequences of ~120–500 nucleotides that exhibit genus-specific secondary structures, and can either be identical at the two ends of the genome (homotelomeric) or can differ in size, sequence and predicted secondary structure (heterotelomeric). Homotelomeric viruses package DNA strands of both senses (into separate capsids) whereas heterotelomeric viruses generally package predominantly negative-sense DNA (discussed in references 5 and 6). All parvoviruses encode two major gene complexes: the non-structural (or rep) gene that encodes the replication initiator protein (called NS1 or Rep), and the VP (or cap) gene, which encodes a nested set of ~2–6 size variants derived from the C-terminus of the single VP protein sequence. Members of the Parvovirinae also encode a few (1–4) small genus-specific ancillary proteins that are variably distributed throughout the genome, show little sequence homology to each other, and appear to serve an array of different functions in each genus (references 2–6). Viruses in most genera are mono-sense, meaning that both viral genes are transcribed in a single direction from open reading frames in the same (positive-sense) DNA strand, but members of one genus of homotelomeric invertebrate viruses (genus Ambidensovirus) show ambisense organization, with the NS and capsid proteins being transcribed in opposite directions from the 5’-ends of the two complementary DNA strands (see reference 1 and 13).
The major non-structural protein, NS1, is a site- and strand-specific endonuclease belonging to the HuH protein superfamily,14 and also carries a AAA+ SF3 helicase domain.15 NS1 initiates and drives the viral “rolling hairpin” replication mechanism (RHR), which is a linear adaptation of the more-common “rolling-circle” replication strategy used by many small circular prokaryotic and viral replicons. RHR is a unidirectional mechanism that displaces a single, continuous DNA strand, which rapidly folds and refolds to generate a series of concatemeric duplex replication intermediates. Unit length genomes are then excised from these intermediates by the NS1 endonuclease (reviewed in references 5 and 6), and packaged 3’-to-5’ into preformed empty capsids driven by the SF3 helicase activity of NS1/Rep.16
Viral replication is nuclear. Entry into the host cell is achieved by attachment to host receptors, which mediates clathrin-mediated endocytosis. Replication follows the rolling-hairpin model. DNA-templated transcription, with some alternative splicing mechanism is the method of transcription. The virus exits the host cell by nuclear pore export. Vertebrates and insects serve as the natural host. Transmission routes are fecal-oral and respiratory.17
|Genus||Host Details||Tissue Tropism||Entry Details||Release Details||Replication Site||Assembly Site||Transmission|
|Amdoparvovirus||Mammals: minks, ferrets, foxes||None||Clathrin-mediated endocytosis||Budding||Nucleus||Nucleus||Unknown|
|Brevidensovirus||Insects: diptera||None||Clathrin-mediated endocytosis||Budding||Nucleus||Nucleus||Unknown|
|Bocaparvovirus||Humans; cows; dogs||None||Clathrin-mediated endocytosis||Budding||Nucleus||Nucleus||Aerosol|
|Dependoparvovirus||Humans; vertebrates||None||Clathrin-mediated endocytosis||Budding||Nucleus||Nucleus||Aerosol; helper virus: adenovirus; helper virus: herpesvirus|
|Aveparvovirus||Vertebrates||None||Clathrin-mediated endocytosis||Budding||Nucleus||Nucleus||Aerosol; oral-fecal|
|Iteradensovirus||Insects: lepidoptera||None||Clathrin-mediated endocytosis||Budding||Nucleus||Nucleus||Unknown|
|Ambidensovirus||Insects: blattodea||None||Clathrin-mediated endocytosis||Budding||Nucleus||Nucleus||Unknown|
This taxonomy was last updated by the International Committee on Virus Taxonomy (ICTV) Parvoviridae Study Group early in 2014, as detailed in references 1 and 12. The family is divided into two subfamilies: Parvovirinae, which infect vertebrates and Densovirinae, which infect invertebrates. Each subfamily has been subdivided into several genera.
To date, very few viruses from the Densovirinae have been studied and sequenced, so the above taxonomy may poorly reflect the true diversity of this subfamily. Currently, all recognized members of genus Ambidensovirus, Brevidensovirus and Iterodensovirus infect insects, while the hepan- and penstyldensoviruses infect decapod shrimp. However, recently a virus was isolated that appears to infect sea-stars and perhaps some other echinoderms18 that would be classified as a member of genus Ambidensovirus according to current ICTV genus demarcation criteria.
Currently, viruses that infect humans are recognized in 5 genera: Bocaparvovirus (human bocavirus 1–4, HboV1–4), Dependoparvovirus (adeno-associated virus 1–5, AAV1–5), Erythroparvovirus (parvovirus B19, B19), Protoparvovirus (Bufavirus 1–2, BuV1–2) and Tetraparvovirus (human parvovirus 4 G1–3, PARV4 G1–3).
Since databases contain vast numbers of sequences that might be considered parvoviral in origin but are not real viruses, the Parvoviridae Study group cite the following criteria (references 1 and 12) that must be established before a new viral sequence can be considered for recognition in the family: "In order for an agent to be classified in the family Parvoviridae, it must be judged to be an authentic parvovirus on the basis of having been isolated and sequenced or, failing this, on the basis of having been sequenced in tissues, secretions, or excretions of unambiguous host origin, supported by evidence of its distribution in multiple individual hosts in a pattern that is compatible with dissemination by infection. The sequence must be in one piece, contain all the nonstructural (NS) and virus particle (VP) coding regions, and meet the size constraints and motif patterns typical of the family."
This means that partial coding sequences or sequences from a single host animal, with no evidence of virus exposure in the rest of the population, will not be considered sufficiently validated. Samples from feces are particularly problematic because they may be derived from food and so do not have an unequivocal host animal. Similarly, samples from aquatic animals that are also present in the surrounding environment are difficult to attribute until they can be shown to directly infect other members of the presumed host species. Despite these caveats, every year many new viruses are identified that merit recognition, so that the published taxonomy always trails the leading edge of the field.
For example, a candidate parvovirus has recently been isolated by sequencing a histocytic sarcoma in a slow loris (Nycticebus coucang).19 The relationship between the virus and the sarcoma was not clear.
- ICTV. "Virus Taxonomy: 2014 Release". Retrieved 15 June 2015.
- Berns KI, Parrish CR. 2013. Parvoviridae. In Fields Virology, ed. DM Knipe, P Howley. Philadelphia: Lippincott Williams & Wilkins. 6th ed
- Halder S, Ng R, Agbandje-McKenna M. 2012. Parvoviruses: structure and infection. Future Virol. 7:253–7
- Agbandje-McKenna M, Kleinschmidt J. 2011. AAV capsid structure and cell interactions. Methods Mol.Biol. 807:47–92
- Cotmore SF, Tattersall P. 2013. Parvovirus diversity and DNA damage responses. In Cold Spring Harb. Perspect. Biol. 5:a01298
- Cotmore, S.F. and Tattersall, P. 2014. Parvoviruses: small does not mean simple. Annual Review of Virology. Vol 1: 517–537. http://www.annualreviews.org/doi/abs/10.1146/annurev-virology-031413-085444
- Huang Q, Deng X, Yan Z, Cheng F, Luo Y, Shen W, Lei-Butters DC, Chen AY, Li Y, Tang L, Söderlund-Venermo M, Engelhardt JF, Qiu J. 2012. Establishment of a reverse genetics system for studying human bocavirus in human airway epithelia. PLoS Pathog.;8(8):e1002899
- Meriluoto M, Hedman L, Tanner L, Simell V, Makinen M, et al. 2012. Association of human bocavirus 1 infection with respiratory disease in childhood follow-up study, Finland. Emerg. Infect. Dis. 18:264–71
- Truyen U, Parrish CR. 2013. Feline panleukopenia virus: its interesting evolution and current problems in immunoprophylaxis against a serious pathogen. Vet. Microbiol. 165:29–32
- Zadori Z, Szelei J, LacosteMC, Li Y, Gariepy S, et al. 2001. A viral phospholipase A2 is required for parvovirus infectivity. Dev. Cell 1:291–302
- Farr GA, Zhang LG, Tattersall P. 2005. Parvoviral virions deploy a capsid-tethered lipolytic enzyme to breach the endosomal membrane during cell entry. Proc. Natl. Acad. Sci. USA 102:17148–53
- Cotmore SF, Agbandje-McKenna M, Chiorini JA, Mukha DV, Pintel DJ, Qiu J, Soderlund-Venermo M, Tattersall P, Tijssen P, Gatherer D, Davison AJ. 2014. The family Parvoviridae.Arch. Virol. 159:1239–1247
- Hickman AB, Ronning DR, Perez ZN, Kotin RM, Dyda F. 2004. The nuclease domain of adeno associated virus Rep coordinates replication initiation using two distinct DNA recognition interfaces. Mol. Cell 13:403–14
- James JA, Aggarwal AK, Linden RM, Escalante CR. 2004. Structure of adeno-associated virus type 2 Rep40-ADP complex: insight into nucleotide recognition and catalysis by superfamily 3 helicases. Proc. Natl. Acad. Sci. USA 101:12455–60
- King JA, Dubielzig R, Grimm D, Kleinschmidt JA. 2001. DNA helicase–mediated packaging of adeno-associated virus type 2 genomes into preformed capsids. EMBO J. 20:3282–91
- "Viral Zone". ExPASy. Retrieved 15 June 2015.
- Hewson I, Button JB, Gudenkauf BM, Miner B, Newton AL, Gaydos JK, Wynne J, Groves CL, Hendler G, Murray M, Fradkin S, Breitbart M, Fahsbender E, Lafferty KD, Kilpatrick AM, Miner CM, Raimondi P, Lahner L, Friedman CS, Daniels S, Haulena M, Marliave J, Burge CA, Eisenlord ME, Harvell CD. 2014. Proc Natl Acad Sci U S A. 111(48):17278–83
- Canuti M, Williams CV, Gadi SR, Jebbink MF, Oude Munnink BB, Jazaeri Farsani SM, Cullen JM, van der Hoek L (2014) Persistent viremia by a novel parvovirus in a slow loris (Nycticebus coucang) with diffuse histiocytic sarcoma. Front Microbiol 5:655. doi: 10.3389/fmicb.2014.00655