Parvoviruses are a family of
animal virus
Animal viruses are viruses that infect animals. Viruses infect all cellular life and although viruses infect every animal, plant, fungus and protist species, each has its own specific range of viruses that often infect only that species.
Vertebra ...
es that constitute the family ''Parvoviridae''. They have linear, single-stranded DNA (ssDNA) genomes that typically contain two genes encoding for a replication initiator protein, called NS1, and the protein the viral capsid is made of. The coding portion of the genome is flanked by
telomere
A telomere (; ) is a region of repetitive nucleotide sequences associated with specialized proteins at the ends of linear chromosomes. Although there are different architectures, telomeres, in a broad sense, are a widespread genetic feature mos ...
s at each end that form into
hairpin loops that are important during replication. Parvovirus virions are small compared to most viruses, at 23–28 nanometers in diameter, and contain the genome enclosed in an icosahedral capsid that has a rugged surface.
Parvoviruses enter a host cell by
endocytosis
Endocytosis is a cellular process in which substances are brought into the cell. The material to be internalized is surrounded by an area of cell membrane, which then buds off inside the cell to form a vesicle containing the ingested material. E ...
, travelling to the nucleus where they wait until the cell enters its replication stage. At that point, the genome is uncoated and the coding portion is replicated. Viral
messenger RNA
In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of synthesizing a protein.
mRNA is created during the p ...
(mRNA) is then
transcribed and
translated
Translation is the communication of the meaning of a source-language text by means of an equivalent target-language text. The English language draws a terminological distinction (which does not exist in every language) between ''transla ...
, resulting in NS1 initiating replication. During replication, the hairpins repeatedly unfold, are replicated, and refold to change the direction of replication to progress back and forth along the genome in a process called
rolling hairpin replication Rolling hairpin replication (RHR) is a unidirectional, strand displacement form of DNA replication used by parvoviruses, a group of viruses that constitute the family ''Parvoviridae''. Parvoviruses have linear, single-stranded DNA (ssDNA) genomes in ...
that produces a molecule containing numerous copies of the genome. Progeny ssDNA genomes are excised from this concatemer and packaged into capsids. Mature virions leave the cell by
exocytosis
Exocytosis () is a form of active transport and bulk transport in which a cell transports molecules (e.g., neurotransmitters and proteins) out of the cell ('' exo-'' + ''cytosis''). As an active transport mechanism, exocytosis requires the use o ...
or
lysis
Lysis ( ) is the breaking down of the membrane of a cell, often by viral, enzymic, or osmotic (that is, "lytic" ) mechanisms that compromise its integrity. A fluid containing the contents of lysed cells is called a ''lysate''. In molecular bio ...
.
Parvoviruses are believed to be descended from ssDNA viruses that have circular genomes that form a loop because these viruses encode a replication initiator protein that is related to NS1 and have a similar replication mechanism. Another group of viruses called
bidnaviruses appear to be descended from parvoviruses. Within the family, three subfamilies, 26 genera, and 126 species are recognized. ''Parvoviridae'' is the sole family in the order ''Piccovirales'', which is the sole order in the class ''Quintoviricetes''. This class is assigned to the phylum ''
Cossaviricota
''Cossaviricota'' is a phylum of viruses.
Classes
The following classes are recognized:
* '' Mouviricetes''
* ''Papovaviricetes
''Papovaviricetes'' is a class of viruses. The class shares the name of an abolished family, ''Papovaviridae'', ...
'', which also includes
papillomavirus
''Papillomaviridae'' is a family of non- enveloped DNA viruses whose members are known as papillomaviruses. Several hundred species of papillomaviruses, traditionally referred to as "types", have been identified infecting all carefully inspected ...
es,
polyomavirus
''Polyomaviridae'' is a family of viruses whose natural hosts are primarily mammals and birds. As of 2020, there are six recognized genera and 117 species, five of which are unassigned to a genus. 14 species are known to infect humans, while othe ...
es, and bidnaviruses.
A variety of diseases in animals are caused by parvoviruses. Notably, the
canine parvovirus
Canine parvovirus (also referred to as CPV, CPV2, or parvo) is a contagious virus mainly affecting dogs. CPV is highly contagious and is spread from dog to dog by direct or indirect contact with their feces. Vaccines can prevent this infection, ...
and
feline parvovirus
''Carnivore protoparvovirus 1'' (CPPV 1) is a species of parvovirus that infects carnivorans. It causes a highly contagious disease in both dogs and cats separately. The disease is generally divided into two major genogroups: CPV-1 containing the ...
cause severe disease in dogs and cats, respectively. In pigs, the
porcine parvovirus
Porcine parvovirus (PPV), a virus in the species ''Ungulate protoparvovirus 1'' of genus ''Protoparvovirus'' in the virus family ''Parvoviridae'', causes reproductive failure of swine characterized by embryonic and fetal infection and death, us ...
is a major cause of infertility. Human parvoviruses are less severe, the two most notable being
parvovirus B19
Primate erythroparvovirus 1, generally referred to as B19 virus (B19V), parvovirus B19 or sometimes erythrovirus B19, is the first (and until 2005 the only) known human virus in the family ''Parvoviridae'', genus ''Erythroparvovirus''; it measur ...
, which causes a variety of illnesses including
fifth disease
Erythema infectiosum, fifth disease, or slapped cheek syndrome is one of several possible manifestations of infection by parvovirus B19. Fifth disease typically presents as a rash and is more common in children. While parvovirus B19 can affect hu ...
in children, and
human bocavirus 1, which is a common cause of acute respiratory tract illness, especially in young children. In medicine, recombinant
adeno-associated virus
Adeno-associated viruses (AAV) are small viruses that infect humans and some other primate species. They belong to the genus ''Dependoparvovirus'', which in turn belongs to the family ''Parvoviridae''. They are small (approximately 26 nm in di ...
es (AAV) have become an important vector for delivering genes to the cell nucleus during
gene therapy
Gene therapy is a medical field which focuses on the genetic modification of cells to produce a therapeutic effect or the treatment of disease by repairing or reconstructing defective genetic material. The first attempt at modifying human DN ...
.
Animal parvoviruses were first discovered in the 1960s, including
minute virus of mice
Minute virus of mice (MVM) is the exemplar virus of the species ''Rodent protoparvovirus 1'', in the genus ''Protoparvovirus'' of the ''Parvoviridae'' family of viruses. MVM exists in multiple variant forms including MVMp, which is the prototype ...
, which is frequently used to study parvovirus replication. Many AAVs were also discovered during this time period and research on them over time has revealed their benefit as a form of medicine. The first pathogenic human parvovirus to be discovered was parvovirus B19 in 1974, which became associated with various diseases throughout the 1980s. Parvoviruses were first classified as the genus ''Parvovirus'' in 1971 but were elevated to family status in 1975. They take their name from the
Latin
Latin (, or , ) is a classical language belonging to the Italic branch of the Indo-European languages. Latin was originally a dialect spoken in the lower Tiber area (then known as Latium) around present-day Rome, but through the power of the ...
word ''parvum'', meaning 'small' or 'tiny', referring to the small size of the virus's virions.
Genome
Parvoviruses have linear, single-stranded DNA (ssDNA) genomes that are about 4–6 kilobases (kb) in length. The parvovirus genome typically contains two genes, termed the NS/rep gene and the VP/cap gene.
The NS gene encodes the non-structural (NS) protein NS1, which is the replication initiator protein, and the VP gene encodes the viral protein (VP) that the viral capsid is made of. NS1 contains an
HUH superfamily endonuclease
Endonucleases are enzymes that cleave the phosphodiester bond within a polynucleotide chain. Some, such as deoxyribonuclease I, cut DNA relatively nonspecifically (without regard to sequence), while many, typically called restriction endonucleases ...
domain near its
N-terminus
The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the ami ...
, containing both site-specific binding activity and site-specific nicking activity, and a superfamily 3 (SF3)
helicase
Helicases are a class of enzymes thought to be vital to all organisms. Their main function is to unpack an organism's genetic material. Helicases are motor proteins that move directionally along a nucleic acid phosphodiester backbone, separatin ...
domain toward the
C-terminus
The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein is ...
. Most parvoviruses contain a transcriptional activation domain near the C-terminus that
upregulates transcription from viral
promoters as well as alternate or overlapping
open reading frame
In molecular biology, open reading frames (ORFs) are defined as spans of DNA sequence between the start and stop codons. Usually, this is considered within a studied region of a prokaryotic DNA sequence, where only one of the six possible readin ...
s that encode a small number of supporting proteins involved in different aspects of the viral life cycle.
The coding portion of the genome is flanked at each end by terminal sequences about 116–550 nucleotides (nt) in length that consist of imperfect palindromes folded into
hairpin loop
Stem-loop intramolecular base pairing is a pattern that can occur in single-stranded RNA. The structure is also known as a hairpin or hairpin loop. It occurs when two regions of the same strand, usually complementary in nucleotide sequence wh ...
structures. These hairpin loops contain most of the ''cis''-acting information required for DNA replication and packaging and act as hinges during replication to change the direction of replication. When the genome is converted to double-stranded forms, replication origin sites are created involving sequences in and adjacent to the hairpins.
Genomic DNA strands in mature virions may be
positive-sense or negative-sense. This varies from species to species as some have a preference for packaging strands of one polarity, others package varying proportions, and others package both sense strands at equal proportions. These preferences reflect the efficiency with which progeny strands are synthesized, which in turn reflects the efficiency of specific replication origin sites.
The 3′-end (usually pronounced "three prime end") of a negative sense strand, and the 5′-end (usually pronounced "five prime end") of a positive sense strand, is called the left end, and the 5′-end of the negative sense strand, and the 3′-end of a positive sense strand, is called the right end.
Structure
![4dpv](https://upload.wikimedia.org/wikipedia/commons/e/ef/4dpv.jpg)
Parvovirus virions are 23–28 nanometers (nm) in diameter and consist of the genome enclosed inside a capsid that is
icosahedral
In geometry, an icosahedron ( or ) is a polyhedron with 20 faces. The name comes and . The plural can be either "icosahedra" () or "icosahedrons".
There are infinitely many non- similar shapes of icosahedra, some of them being more symmetrica ...
in shape with a rugged surface. The capsid is composed of 60 structurally equivalent polypeptide chains derived from the C-terminal end of a VP protein's sequence, interlocking extensively to form an icosahedron with 60 asymmetric, superficial triangular units. These units have 3-fold
radial symmetry
Symmetry in biology refers to the symmetry observed in organisms, including plants, animals, fungi, and bacteria. External symmetry can be easily seen by just looking at an organism. For example, take the face of a human being which has a pla ...
at two vertices and 5-fold radial symmetry at one, with 2-fold radial symmetry at the line opposite of the 5-fold vertex and a 2/5 circular fold wall surrounding the point of the 5-fold vertex. Twenty 3-fold vertices, thirty 2-fold lines, and twelve 5-fold vertices exist per capsid, the latter corresponding to the 12 vertices of the icosahedron.
Typical features of the capsid surface include depressions at each 2-fold axis, elevated protrusions surrounding the 3-fold axes, and raised cylindrical projections made of five beta-barrels
surrounded by canyon-like depressions at the 5-fold axes. Each of these cylinders potentially contains an opening to connect the exterior of the capsid to the interior, which mediates entry and exit of the genome. About 20 nucleotides from the 5′-end of the genome may remain exposed outside of the capsid carrying a copy of NS1 bound to the 5′-end, which is a result of how the genome is synthesized and packaged.
Varying sizes of the VP protein are expressed for different parvoviruses, the smaller ones, VP2–5, being expressed at a higher frequency than the large size, VP1. The smaller VPs share a common C-terminus with different N-terminus lengths due to truncation. For VP1, the N-terminus is extended to contain regions important in the replication cycle, and it is incorporated into the capsid, typically 5–10 per capsid, with the common C-terminus responsible for assembling capsids.
Each VP monomer contains a core beta-barrel structure called the
jelly roll motif
The jelly roll or Swiss roll fold is a protein fold or supersecondary structure composed of eight beta strands arranged in two four-stranded sheets. The name of the structure was introduced by Jane S. Richardson in 1981, reflecting its resemblan ...
of eight strands arranged in two adjacent antiparallel beta sheets, labeled CHEF and BIDG after the individual strands, the latter forming the interior surface of the capsid. Individual beta strands are connected by loops that have varying length, sequence, and conformation, and most of these loops extend toward the exterior surface, giving parvoviruses their unique, rough surface. Related parvoviruses share their surface topologies and VP protein folds to a greater degree than their sequence identities, so the structure of the capsid and capsid protein are useful indicators of phylogeny.
Life cycle
Parvoviruses enter cells by
endocytosis
Endocytosis is a cellular process in which substances are brought into the cell. The material to be internalized is surrounded by an area of cell membrane, which then buds off inside the cell to form a vesicle containing the ingested material. E ...
, using a variety of cellular receptors to bind to the host cell. In
endosome
Endosomes are a collection of intracellular sorting organelles in eukaryotic cells. They are parts of endocytic membrane transport pathway originating from the trans Golgi network. Molecules or ligands internalized from the plasma membrane can ...
s, many parvoviruses undergo a change in conformation so that the
phospholipase
A phospholipase is an enzyme that hydrolyzes phospholipids into fatty acids and other lipophilic substances. Acids trigger the release of bound calcium from cellular stores and the consequent increase in free cytosolic Ca2+, an essential step in ...
A2 (PLA) domain on the VP1 N-termini are exposed so the virion can penetrate lipid bilayer membranes. Intracellular trafficking of virions varies, but virions ultimately arrive to the nucleus, inside of which the genome is uncoated from the capsid. Based on studies of minute virus of mice (MVM), the genome is ejected from the capsid in a 3′-to-5′ direction from one of the openings in the capsid, leaving the 5′-end of the DNA attached to the capsid.
Parvoviruses lack the ability to induce cells into their
DNA replication
In molecular biology, DNA replication is the biological process of producing two identical replicas of DNA from one original DNA molecule. DNA replication occurs in all living organisms acting as the most essential part for biological inheritanc ...
stage, called S-phase, so they must wait in the nucleus until the host cell enters S-phase on its own. This makes cell populations that divide rapidly, such as fetal cells, an excellent environment for parvoviruses. Adeno-associated viruses (AAV) are dependent on helper viruses, which may be an
adenovirus
Adenoviruses (members of the family ''Adenoviridae'') are medium-sized (90–100 nm), nonenveloped (without an outer lipid bilayer) viruses with an icosahedral nucleocapsid containing a double-stranded DNA genome. Their name derives from the ...
or a
herpesvirus
''Herpesviridae'' is a large family of DNA viruses that cause infections and certain diseases in animals, including humans. The members of this family are also known as herpesviruses. The family name is derived from the Greek word ''ἕρπειν ...
, since coinfection alters the cellular environment to allow for replication.
In the absence of coinfection, AAV's genome is integrated into the host cell's genome until coinfection occurs.
Infected cells that enter S-phase are forced to synthesize viral DNA and cannot leave S-phase. Parvoviruses establish replication foci in the nucleus that grow progressively larger as infection progresses.
Once a cell enters S-phase and the genome is uncoated, a host
DNA polymerase
A DNA polymerase is a member of a family of enzymes that catalyze the synthesis of DNA molecules from nucleoside triphosphates, the molecular precursors of DNA. These enzymes are essential for DNA replication and usually work in groups to create ...
uses the 3′-end of the 3′ hairpin as a primer to synthesize a complementary DNA strand for the coding portion of the genome, which is
connected
Connected may refer to:
Film and television
* ''Connected'' (2008 film), a Hong Kong remake of the American movie ''Cellular''
* '' Connected: An Autoblogography About Love, Death & Technology'', a 2011 documentary film
* ''Connected'' (2015 TV ...
to the 5′-end of the 5′ hairpin.
Messenger RNA
In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of synthesizing a protein.
mRNA is created during the p ...
(mRNA) that encodes NS1 is then transcribed from the genome by the DNA polymerase, capped and polyadenylated, and translated by host ribosomes to synthesize NS1.
If proteins are encoded in multiple co-linear frames, then alternative splicing, suboptimal translation initiation, or
leaky scanning
Leaky scanning is a mechanism used during the initiation phase of eukaryotic translation that enables regulation of gene expression. During initiation, the small 40S ribosomal subunit (as a 43S PIC) "scans" or moves in a 5' --> 3' direction along ...
may be used to translate different gene products.
Parvoviruses replicate their genome via
rolling hairpin replication Rolling hairpin replication (RHR) is a unidirectional, strand displacement form of DNA replication used by parvoviruses, a group of viruses that constitute the family ''Parvoviridae''. Parvoviruses have linear, single-stranded DNA (ssDNA) genomes in ...
, a unidirectional, strand displacement form of DNA replication that is initiated by NS1. Replication begins once NS1 binds to and makes a nick in a replication origin site in the duplex DNA molecule at the end of one hairpin. Nicking releases the 3′-end of the nicked strand as a free
hydroxyl
In chemistry, a hydroxy or hydroxyl group is a functional group with the chemical formula and composed of one oxygen atom covalently bonded to one hydrogen atom. In organic chemistry, alcohols and carboxylic acids contain one or more hydroxy ...
(-OH) to prime DNA synthesis
with NS1 remaining attached to the 5′-end.
The nick causes the adjacent hairpin to unfold into a linear, extended form. At the 3′-OH, a replication fork is established using NS1's helicase activity, and the extended telomere is replicated by the DNA polymerase. The two telomere strands then refold back in on themselves to their original configurations, which repositions the replication fork to switch templates to the other strand and move in the opposite direction toward the other end of the genome.
Parvoviruses vary in whether the termini are similar or the same, called homotelomeric parvoviruses, or different, called heterotelomeric parvoviruses. In general, homotelomeric parvoviruses, such as AAV and B19, replicate both ends of their genome through the aforementioned process, called terminal resolution, and their hairpin sequences are contained within larger (inverted) terminal repeats. Heterotelomeric viruses, such as minute virus of mice (MVM), replicate one end by terminal resolution and the other end via an asymmetric process called junction resolution
so that the correct orientation of the telomere can be copied.
During asymmetric junction resolution, the duplex extended-form telomeres refold in on themselves into a cruciform shape. A replication origin site on the lower strand of the right arm of the cruciform is nicked by NS1, leading to the lower arm of the cruciform unfolding into its linear extended form. A replication fork established at the nick site moves down the extended lower arm to copy the lower arm's sequence. The two strands of the lower arm then refold to reposition the replication fork to go back toward the other end, displacing the upper strand in the process.
The back and forth, end-to-end pattern of rolling hairpin replication produces a concatemer containing multiple copies of the genome.
NS1 periodically makes nicks in this molecule and, through a combination of terminal resolution and junction resolution, individual strands of the genome are excised from the concatemer.
Excised genomes may either be recycled for further rounds of replication or packaged into progeny capsids.
Translation of mRNA containing VP proteins leads to the accumulation of capsid proteins in the nucleus that assemble into these empty capsids.
Genomes are encapsidated at one of the capsid's vertices through a portal,
potentially the one opposite the portal used to expel the genome.
Once complete virions have been constructed, they may be exported from the nucleus to the exterior of the cell before disintegration of the nucleus. Disruption of the host cell environment may also occur later on in the infection. This results in cell
lysis
Lysis ( ) is the breaking down of the membrane of a cell, often by viral, enzymic, or osmotic (that is, "lytic" ) mechanisms that compromise its integrity. A fluid containing the contents of lysed cells is called a ''lysate''. In molecular bio ...
via
necrosis
Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which result in the unregulated dige ...
or
apoptosis
Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...
, which releases virions to the outside of the cell.
Evolution
Parvoviruses are believed to be descended from ssDNA viruses that have a circular genome that forms a loop and which replicate via
rolling circle replication
Rolling circle replication (RCR) is a process of unidirectional nucleic acid replication that can rapidly synthesize multiple copies of circular molecules of DNA or RNA, such as plasmids, the genomes of bacteriophages, and the circular RNA genom ...
, which is similar to rolling hairpin replication. These circular ssDNA viruses encode a replication initiator protein that is related to and possesses many of the same characteristics as the replication initiator protein of parvoviruses, such as the HUH endonuclease domain and the SF3 helicase domain.
In contrast to these other replication initiator proteins, NS1 shows only vestigial traces of being able to perform ligation, which is a key part of rolling circle replication. The ''
Bidnaviridae'' family, which are also linear ssDNA viruses, appear to be descended from a parvovirus that had its genome integrated into the genome of a
polinton Polintons (also called Mavericks) are large DNA transposons which contain genes with homology to viral proteins and which are often found in eukaryotic genomes. They were first discovered in the mid-2000s and are the largest and most complex known ...
, a type of DNA
transposon
A transposable element (TE, transposon, or jumping gene) is a nucleic acid sequence in DNA that can change its position within a genome, sometimes creating or reversing mutations and altering the cell's genetic identity and genome size. Transpo ...
related to viruses in the realm ''
Varidnaviria
''Varidnaviria'' is a realm of viruses that includes all DNA viruses that encode major capsid proteins that contain a vertical jelly roll fold. The major capsid proteins (MCP) form into pseudohexameric subunits of the viral capsid, which stores t ...
''.
Based on phylogenetic analysis of the SF3 helicase, parvoviruses split into two branches early in their evolutionary history, one of which contains viruses assigned to the subfamily ''Hamaparvovirinae''. The other branch split into two sublineages that constitute the other two subfamilies, ''Densovirinae'' and ''Parvovirinae''.
Parvoviruses in the ''Hamaparvovirinae'' lineage are likely all heterotelomeric, ''Densovirinae'' are exclusively homotelomeric, and ''Parvovirinae'' varies.
Telomere sequences have significant complexity and diversity, suggesting that many species have co-opted them to perform additional functions.
Parvoviruses are also considered to have high rates of genetic
mutation
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...
s and
recombinations.
Classification
Parvoviruses constitute the family ''Parvoviridae''. The family is the sole family in the order ''Piccovirales'', which is the sole order in the class ''Quintoviricetes''. The class ''Quintoviricetes'' belongs to the phylum ''
Cossaviricota
''Cossaviricota'' is a phylum of viruses.
Classes
The following classes are recognized:
* '' Mouviricetes''
* ''Papovaviricetes
''Papovaviricetes'' is a class of viruses. The class shares the name of an abolished family, ''Papovaviridae'', ...
'', which also includes
papillomavirus
''Papillomaviridae'' is a family of non- enveloped DNA viruses whose members are known as papillomaviruses. Several hundred species of papillomaviruses, traditionally referred to as "types", have been identified infecting all carefully inspected ...
es,
polyomavirus
''Polyomaviridae'' is a family of viruses whose natural hosts are primarily mammals and birds. As of 2020, there are six recognized genera and 117 species, five of which are unassigned to a genus. 14 species are known to infect humans, while othe ...
es, and bidnaviruses. ''Cossaviricota'' is included in the kingdom ''
Shotokuvirae
''Shotokuvirae'' is a kingdom of virus
A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bac ...
'', which is assigned to the realm ''
Monodnaviria
''Monodnaviria'' is a realm of viruses that includes all single-stranded DNA viruses that encode an endonuclease of the HUH superfamily that initiates rolling circle replication of the circular viral genome. Viruses descended from such viruses a ...
''. ''Parvoviridae'' belongs to Group II: ssDNA viruses in the
Baltimore classification
Baltimore classification is a system used to classify viruses based on their manner of messenger RNA (mRNA) synthesis. By organizing viruses based on their manner of mRNA production, it is possible to study viruses that behave similarly as a di ...
system, which groups viruses together based on their manner of mRNA synthesis. Within ''Parvoviridae'', three subfamilies, 26 genera, and 126 species are recognized as of 2020 (-''virinae'' denotes subfamily and -''virus'' denotes genus):
* ''
Densovirinae
''Densovirinae'' is a subfamily of single-stranded DNA viruses in the family ''Parvoviridae''. The subfamily has 11 recognized genera and 21 species. Densoviruses are known to infect members of insect orders ''Blattodea'', ''Diptera'', ''Hemipte ...
'' (11 genera, 21 species)
::''
Aquambidensovirus'' (3 species)
::''
Blattambidensovirus'' (1 species)
::''
Diciambidensovirus'' (1 species)
::''
Hemiambidensovirus'' (2 species)
::''
Iteradensovirus'' (5 species)
::''
Miniambidensovirus'' (1 species)
::''
Muscodensovirus'' (1 species)
::''
Pefuambidensovirus'' (1 species)
::''
Protoambidensovirus'' (2 species)
::''
Scindoambidensovirus'' (3 species)
::''
Tetuambidensovirus'' (1 species)
* ''
Hamaparvovirinae'' (5 genera, 21 species)
::''
Brevihamaparvovirus'' (2 species)
::''
Chaphamaparvovirus'' (16 species)
::''
Hepanhamaparvovirus'' (1 species)
::''
Ichthamaparvovirus'' (1 species)
::''
Penstylhamaparvovirus'' (1 species)
* ''
Parvovirinae
''Parvovirinae'' is a subfamily of viruses in the family ''Parvoviridae''. There are ten genera and 84 species assigned to this subfamily.
Taxonomy
The following 10 genera are recognized:
*'' Amdoparvovirus''
*'' Artiparvovirus''
*'' Aveparvovi ...
'' (10 genera, 84 species)
::''
Amdoparvovirus'' (5 species)
::''
Artiparvovirus'' (1 species)
::''
Aveparvovirus'' (3 species)
::''
Bocaparvovirus
''Bocaparvovirus'' is a genus of viruses in the subfamily ''Parvovirinae'' of the virus family ''Parvoviridae''. Humans, cattle, and dogs serve as natural hosts. There are 28 species in this genus. Diseases associated with this genus include, in ...
'' (28 species)
::''
Copiparvovirus'' (7 species)
::''
Dependoparvovirus
''Dependoparvovirus'' (formerly ''Dependovirus'' or Adeno-associated virus group) is a genus in the subfamily ''Parvovirinae'' of the virus family ''Parvoviridae''; they are Group II viruses according to the Baltimore classification. Some depend ...
'' (11 species)
::''
Erythroparvovirus'' (7 species)
::''
Loriparvovirus'' (1 species)
::''
Protoparvovirus
''Protoparvovirus'' is a genus of viruses in the ''Parvovirinae'' subfamily of the virus family ''Parvoviridae''. Vertebrates serve as natural hosts. There are 15 species in the genus including ''Rodent protoparvovirus 1'' for which the exemplar ...
'' (15 species)
::''
Tetraparvovirus
Tetraparvovirus are a genus of viruses in the family ''Parvoviridae''. There are six recognized species: '' Chiropteran tetraparvovirus 1'', '' Primate tetraparvovirus 1'', '' Ungulate tetraparvovirus 1'', '' Ungulate tetraparvovirus 2'', '' Ungu ...
'' (6 species)
Parvoviruses are assigned to the same species if they share at least 85% of their protein sequence identities. Species are grouped together in a genus based on phylogeny of the NS1 and SF3 helicase domains, as well as similarity of NS1 sequence identity and coverage. If these criteria aren't satisfied, then genera can still be established provided that common ancestry is supported. The three subfamilies are distinguished based on phylogeny of the SF3 helicase domain, which corresponds to host range: viruses in ''Densovirinae'' infect invertebrates, viruses in ''Hamaparvovirinae'' infect invertebrates and vertebrates, and viruses in ''Parvovirinae'' infect vertebrates.
Disease
![B19 virus](https://upload.wikimedia.org/wikipedia/commons/4/48/B19_virus.png)
In humans, the most prominent parvoviruses that cause disease are
parvovirus B19
Primate erythroparvovirus 1, generally referred to as B19 virus (B19V), parvovirus B19 or sometimes erythrovirus B19, is the first (and until 2005 the only) known human virus in the family ''Parvoviridae'', genus ''Erythroparvovirus''; it measur ...
and
human bocavirus 1. B19 infection is often asymptomatic but can manifest in a variety of ways, including
Fifth disease
Erythema infectiosum, fifth disease, or slapped cheek syndrome is one of several possible manifestations of infection by parvovirus B19. Fifth disease typically presents as a rash and is more common in children. While parvovirus B19 can affect hu ...
with its characteristic rash in children, persistent
anemia
Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, th ...
in immunocompromised persons and in people who have underlying
hemoglobinopathies
Hemoglobinopathy is the medical term for a group of inherited blood disorders and diseases that primarily affect red blood cells. They are single-gene disorders and, in most cases, they are inherited as autosomal co-dominant traits.
There are t ...
,
transient
aplastic crises,
hydrops fetalis
Hydrops foetalis or hydrops fetalis is a condition in the fetus characterized by an accumulation of fluid, or edema, in at least two fetal compartments. By comparison, hydrops allantois or hydrops amnion is an accumulation of excessive fluid in ...
in pregnant women, and
arthropathy
An arthropathy is a disease of a joint. Types
Arthritis is a form of arthropathy that involves inflammation of one or more joints, while the term arthropathy may be used regardless of whether there is inflammation or not.
Joint diseases can be cla ...
. Human bocavirus 1 is a common cause of acute respiratory tract infection, especially in young children, wheezing being a common symptom. Other parvoviruses associated with different diseases in humans include human parvovirus 4 and human bufavirus, though the manner by which these viruses cause disease is unclear.
Carnivore
A carnivore , or meat-eater (Latin, ''caro'', genitive ''carnis'', meaning meat or "flesh" and ''vorare'' meaning "to devour"), is an animal or plant whose food and energy requirements derive from animal tissues (mainly muscle, fat and other sof ...
-infecting viruses in the genus ''Protoparvovirus'', in contrast to human parvoviruses, are more life-threatening.
Canine parvovirus
Canine parvovirus (also referred to as CPV, CPV2, or parvo) is a contagious virus mainly affecting dogs. CPV is highly contagious and is spread from dog to dog by direct or indirect contact with their feces. Vaccines can prevent this infection, ...
causes severe illness in dogs, the most common symptom being hemorrhagic enteritis, with up to a 70% mortality rate in pups but usually less than 1% in adults.
Feline parvovirus
''Carnivore protoparvovirus 1'' (CPPV 1) is a species of parvovirus that infects carnivorans. It causes a highly contagious disease in both dogs and cats separately. The disease is generally divided into two major genogroups: CPV-1 containing the ...
, a closely related virus,
likewise causes severe illness in cats along with
panleukopenia.
In pigs,
porcine parvovirus
Porcine parvovirus (PPV), a virus in the species ''Ungulate protoparvovirus 1'' of genus ''Protoparvovirus'' in the virus family ''Parvoviridae'', causes reproductive failure of swine characterized by embryonic and fetal infection and death, us ...
is a major cause of infertility as infection frequently leads to death of the fetus.
Use in medicine
Adeno-associated viruses have become an important vector for
gene therapy
Gene therapy is a medical field which focuses on the genetic modification of cells to produce a therapeutic effect or the treatment of disease by repairing or reconstructing defective genetic material. The first attempt at modifying human DN ...
aimed at treating genetic diseases, such as those caused by a single mutation. The recombinant AAV (rAAV) contains a viral capsid but lacks a complete viral genome. Instead, the typical nucleic acid packaged into the capsid contains a promoter region, the gene of interest, and a terminator region, all contained within two inverted terminal repeats derived from the viral genome. rAAV essentially acts as a container that can traverse the cell membrane and deliver its nucleic acid cargo to the nucleus.
History
Parvoviruses were discovered relatively late in comparison to other prominent virus families, potentially due to their small size. In the late 1950s
and 1960s,
a variety of animal parvoviruses were discovered, including
minute virus of mice
Minute virus of mice (MVM) is the exemplar virus of the species ''Rodent protoparvovirus 1'', in the genus ''Protoparvovirus'' of the ''Parvoviridae'' family of viruses. MVM exists in multiple variant forms including MVMp, which is the prototype ...
,
which has since been used extensively to study rolling hairpin replication. Many AAVs were also discovered during this time period
and research on them led to their first usage in gene therapy in the 1980s. Over time, improvements in aspects such as vector design led to certain AAV gene therapy products reaching clinical efficacy in 2008 and being approved in the following years.
In 1974, the first pathogenic human parvovirus was discovered by
Yvonne Cossart
Yvonne Edna Cossart (14 August 1934 – 16 December 2014) was an Australian virologist, who discovered the parvovirus B19 in 1975.
Cossart graduated from the University of Sydney with a Bachelor of Science in 1957 and MB BS in 1959.
She was a ...
, et al. When testing for the
hepatitis B virus
''Hepatitis B virus'' (HBV) is a partially double-stranded DNA virus, a species of the genus ''Orthohepadnavirus'' and a member of the ''Hepadnaviridae'' family of viruses. This virus causes the disease hepatitis B.
Disease
Despite there bein ...
's surface antigen, one serum sample gave anomalous results and with
electron microscopy
An electron microscope is a microscope that uses a beam of accelerated electrons as a source of illumination. As the wavelength of an electron can be up to 100,000 times shorter than that of visible light photons, electron microscopes have a hi ...
was shown to contain a virus resembling animal parvoviruses. This virus was named B19 after the coding of the serum sample, number 19 in panel B.
B19 was later recognized as a species by the
International Committee on Taxonomy of Viruses
The International Committee on Taxonomy of Viruses (ICTV) authorizes and organizes the taxonomic classification of and the nomenclatures for viruses. The ICTV has developed a universal taxonomic scheme for viruses, and thus has the means to app ...
(ICTV) in 1985, and throughout the 1980s it increasingly became associated with various diseases.
In the ICTV's first report in 1971, parvoviruses were grouped together in the genus ''Parvovirus''.
They were elevated to the rank of family in 1975 and remained unassigned to higher taxa until 2019, when they were assigned to higher taxa up to the highest rank, realm.
The family was reorganized in 2019, departing from the "traditional" invertebrate-vertebrate distinction between ''Densovirinae'' and ''Parvovirinae'' and instead distinguishing the subfamilies based on helicase phylogeny, leading to the establishment of a new subfamily, ''Hamaparvovirinae''.
Etymology
Parvoviruses take their name from
Latin
Latin (, or , ) is a classical language belonging to the Italic branch of the Indo-European languages. Latin was originally a dialect spoken in the lower Tiber area (then known as Latium) around present-day Rome, but through the power of the ...
''parvus'' or ''parvum'', meaning ''small'' or ''tiny'', referring to the small size of parvovirus virions compared to most other viruses.
In the family name ''Parvoviridae'', -''viridae'' is the suffix used for virus families.
The order ''Piccovirales'' takes the first part of its name from the
Italian
Italian(s) may refer to:
* Anything of, from, or related to the people of Italy over the centuries
** Italians, an ethnic group or simply a citizen of the Italian Republic or Italian Kingdom
** Italian language, a Romance language
*** Regional Ita ...
word ''piccolo'', meaning ''small'', and the second part is the suffix used for virus orders. The class ''Quintoviricetes'' takes the first part of its name from the
Galician word ''quinto'', meaning ''fifth'', referring to
fifth disease
Erythema infectiosum, fifth disease, or slapped cheek syndrome is one of several possible manifestations of infection by parvovirus B19. Fifth disease typically presents as a rash and is more common in children. While parvovirus B19 can affect hu ...
(erythema infectiosum) caused by parvovirus B19, and ''viricetes'', the suffix used for virus classes.
References
Bibliography
*
{{Taxonbar, from1=Q13210344, from2=Q12043883
*
Virus families
no:Hundepest
nn:Hundepest