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108-541: See text Parvoviruses are a family of animal viruses 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 telomeres 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

216-514: A scintillation proximity assay , a time resolved fluorescence resonance energy transfer assay, an assay based on flashplate technology, homogenous time-resolved fluorescence quenching assays, and electrochemiluminescence-based helicase assays". With the use of specialized mathematical equations, some of these assays can be utilized to determine how many base paired nucleotides a helicase can break per hydrolysis of 1 ATP molecule. Commercially available diagnostic kits are also available. One such kit

324-520: A "locking" in repair mode. This could cause the helicase to cut DNA segments meant for transcription. Although current evidence points to a defect in the XPD helicase resulting in a loss of flexibility in the protein in cases of Cockayne syndrome, it is still unclear how this protein structure leads to the symptoms described in Cockayne syndrome. In xeroderma pigmentosa, the XPD helicase mutation exists at

432-606: A Holliday junction. RecG releases bound proteins and the PriA helicase facilitates DNA reloading to resume DNA replication. RecG replaces the single-strand binding protein (SSB), which regulates the helicase-fork loading sites during fork regression. The SSB protein interacts with DNA helicases PriA and RecG to recover stalled DNA replication forks. These enzymes must bind to the SSB-helicase to be loaded onto stalled forks. Thermal sliding and DNA duplex binding are possibly supported by

540-414: 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

648-499: A contribution to the survival of hippocampal and cortical structures, affecting memory and learning. This helicase is located on the X chromosome (Xq13.1-q21.1), in the pericentromeric heterochromatin and binds to heterochromatin protein 1 . Studies have shown that ATRX plays a role in rDNA methylation and is essential for embryonic development. Mutations have been found throughout the ATRX protein, with over 90% of them being located in

756-519: A core beta-barrel structure called the jelly roll motif 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

864-457: A duplex strand, as described above, for DNA unwinding. However, local strand separation occurs by a process wherein the helicase enzyme is loaded at any place along the duplex. This is usually aided by a single-strand region of the RNA, and the loading of the enzyme is accompanied with ATP binding. Once the helicase and ATP are bound, local strand separation occurs, which requires binding of ATP but not

972-824: 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. In humans,

1080-586: A greater degree than their sequence identities, so the structure of the capsid and capsid protein are useful indicators of phylogeny. Parvoviruses enter cells by endocytosis , using a variety of cellular receptors to bind to the host cell. In endosomes , many parvoviruses undergo a change in conformation so that the phospholipase A2 (PLA 2 ) 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

1188-489: 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

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1296-432: 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

1404-410: A mortality rate that is affected by the temperature of the water. In hatcheries the diseases are often controlled by increasing the temperature to 15–18 °C. Like all vertebrates, fish suffer from herpes viruses . These ancient viruses have co-evolved with their hosts and are highly species-specific. In fish, they cause cancerous tumours and non-cancerous growths called hyperplasia . Arthropods

1512-467: A reduced reproductive lifespan with chromosomal breaks and translocations, as well as large deletions of chromosomal components, causing genomic instability. Rothmund-Thomson syndrome, also known as poikiloderma congenitale , is characterized by premature aging, skin and skeletal abnormalities, rash, poikiloderma , juvenile cataracts, and a predisposition to cancers such as osteosarcomas. Chromosomal rearrangements causing genomic instability are found in

1620-439: A ring structure are in superfamilies 1 and 2, and ring-forming helicases form part of superfamilies 3 to 6. Helicases are also classified as α or β depending on if they work with single or double-strand DNA ; α helicases work with single-strand DNA and β helicases work with double-strand DNA . They are also classified by translocation polarity. If translocation occurs 3’-5’ the helicase is type A; if translocation occurs 5’-3’ it

1728-431: 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

1836-445: 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 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

1944-418: A type of DNA transposon related to viruses in the realm Varidnaviria . 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

2052-418: 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 (-OH) to prime DNA synthesis with NS1 remaining attached to the 5′-end. The nick causes the adjacent hairpin to unfold into

2160-426: A variety of illnesses including fifth disease 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 viruses (AAV) have become an important vector for delivering genes to the cell nucleus during gene therapy . Animal parvoviruses were first discovered in the 1960s, including minute virus of mice, which

2268-474: 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 -infecting viruses in the genus Protoparvovirus , in contrast to human parvoviruses, are more life-threatening. Canine parvovirus causes severe illness in dogs,

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2376-512: Is a fatal pox virus infection of rabbits: once infected they die within twelve days. The virus was deliberately released in Australia in 1950, in an attempt to control the exponentially growing rabbit population. Rabbits had been brought to the continent in 1859 for sport, and having no natural predators, bred at an extraordinary rate. The infection killed 99.8 percent of rabbits, but by the late 1950s, Australian rabbits started to become immune to

2484-549: Is a grave concern. Baculoviruses are among the best studied of the invertebrate viruses. They infect and kill several species of agricultural pests, and as natural insecticides, they have been used to control insect populations in Brazil and Paraguay such as the velvet bean caterpillar ( Anticarsia gemmatalis ), a pest of soy beans. Viruses are an attractive alternative to chemical pesticides because they are safe to other wildlife and leave no residues. Viruses can also change

2592-451: Is a history of helicase discovery: The common function of helicases accounts for the fact that they display a certain degree of amino acid sequence homology ; they all possess sequence motifs located in the interior of their primary structure , involved in ATP binding, ATP hydrolysis and translocation along the nucleic acid substrate . The variable portion of the amino acid sequence

2700-406: Is achieved through the lowering of the activation barrier ( B {\displaystyle B} ) of each specific action. The activation barrier is a result of various factors, and can be defined by where Factors that contribute to the height of the activation barrier include: specific nucleic acid sequence of the molecule involved, the number of base pairs involved, tension present on

2808-473: Is also deemed "directionality", is defined as the direction (characterized as 5'→3' or 3'→5') of helicase movement on the DNA/RNA single-strand along which it is moving. This determination of polarity is vital in f.ex. determining whether the tested helicase attaches to the DNA leading strand, or the DNA lagging strand. To characterize this helicase feature, a partially duplex DNA is used as the substrate that has

2916-428: Is an organic quencher molecule. The basis of this assay is the "quenching" or repressing of the lanthanide chelate signal by the organic quencher molecule when the two are in close proximity – as they would be when the DNA duplex is in its native state. Upon helicase activity on the duplex, the quencher and lanthanide labels get separated as the DNA is unwound. This loss in proximity negates the quenchers ability to repress

3024-454: Is assigned to the phylum Cossaviricota , which also includes papillomaviruses , polyomaviruses , and bidnaviruses. A variety of diseases in animals are caused by parvoviruses. Notably, the canine parvovirus and feline parvovirus cause severe disease in dogs and cats, respectively. In pigs, the porcine parvovirus is a major cause of infertility. Human parvoviruses are less severe, the two most notable being parvovirus B19 , which causes

3132-601: Is called the right end. Parvovirus virions are 23–28 nanometers (nm) in diameter and consist of the genome enclosed inside a capsid that is icosahedral 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 at two vertices and 5-fold radial symmetry at one, with 2-fold radial symmetry at

3240-546: Is connected to a small number of uncommon genetic cancer disorders in individuals. It participates in transcription, the cell cycle, and DNA repair. According to recent research, missense mutations in the RECQ1 gene may play a role in the development of familial breast cancer. DNA helicases are frequently attracted to regions of DNA damage and are essential for cellular DNA replication, recombination, repair, and transcription. Chemical manipulation of their molecular processes can change

3348-432: Is evidence to suggest that BLM plays a role in rescuing disrupted DNA replication at replication forks. Werner syndrome is a disorder of premature aging, with symptoms including early onset of atherosclerosis and osteoporosis and other age related diseases, a high occurrence of sarcoma, and death often occurring from myocardial infarction or cancer in the 4th to 6th decade of life. Cells of Werner syndrome patients exhibit

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3456-475: 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

3564-513: Is related to the specific features of each helicase. The presence of these helicase motifs allows putative helicase activity to be attributed to a given protein, but does not necessarily confirm it as an active helicase. Conserved motifs do, however, support an evolutionary homology among enzymes. Based on these helicase motifs, a number of helicase superfamilies have been distinguished. Helicases are classified in 6 groups (superfamilies) based on their shared sequence motifs. Helicases not forming

3672-542: Is the Boltzmann constant and T {\displaystyle T} is temperature of the system). Due to this significant activation barrier, its unwinding progression is affected largely by the sequence of nucleic acids within the molecule to unwind, and the presence of destabilization forces acting on the replication fork. Certain nucleic acid combinations will decrease unwinding rates (i.e. guanine and cytosine ), while various destabilizing forces can increase

3780-487: Is the "Trupoint" diagnostic assay from PerkinElmer , Inc. This assay is a time-resolved fluorescence quenching assay that utilizes the PerkinElmer "SignalClimb" technology that is based on two labels that bind in close proximity to one another but on opposite DNA strands. One label is a fluorescent lanthanide chelate, which serves as the label that is monitored through an adequate 96/384 well plate reader. The other label

3888-463: Is the largest group of animals and has shown to be a major reservoir of different viruses, both insect-specific viruses (ISV) and viruses that can infect both vertebrates and invertebrates, more known as arthropod-borne viruses ( arboviruses ). Insect-specific viruses are, as the name reveals, characterised by their incapacity to infect vertebrates. This can be assessed through, viral inoculation of mammalian, avian, or amphibian cell lines. The first (ISV)

3996-542: Is type B. All helicases are members of a P-loop, or Walker motif -containing family. The ATRX gene encodes the ATP-dependent helicase, ATRX (also known as XH2 and XNP) of the SNF2 subgroup family, that is thought to be responsible for functions such as chromatin remodeling, gene regulation, and DNA methylation. These functions assist in prevention of apoptosis, resulting in cortical size regulation, as well as

4104-524: The Baltimore classification 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): Parvoviruses are assigned to the same species if they share at least 85% of their protein sequence identities. Species are grouped together in

4212-401: 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 mutations and recombinations . Parvoviruses constitute

4320-534: The sister chromatid or a homologous non-sister chromatid as template. This repair can result in a crossover (CO) or, more frequently, a non-crossover (NCO) recombinant. In the yeast Schizosaccharomyces pombe the FANCM -family DNA helicase FmI1 directs NCO recombination formation during meiosis. The RecQ-type helicase Rqh1 also directs NCO meiotic recombination. These helicases, through their ability to unwind D-loop intermediates, promote NCO recombination by

4428-460: 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 Tamim.k, N.I Urbi , et al. When testing for the hepatitis B virus 's surface antigen, one serum sample gave anomalous results and with electron microscopy

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4536-497: 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,

4644-552: The BLM gene cause Bloom syndrome, which is characterized by increased cancer risk and other health issues. Mutations in the WRN gene lead to Werner syndrome, a condition characterized by premature aging and an increased risk of age-related diseases. RecQ helicases are crucial for maintaining genomic stability and integrity. They help prevent the accumulation of genetic abnormalities that can lead to diseases like cancer. Genome integrity depends on

4752-453: 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 ,

4860-570: The Latin word parvum, meaning 'small' or 'tiny', referring to the small size of the virus's virions. 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

4968-510: The RecQ DNA helicase family, which includes DNA repair, recombination, replication, and transcription processes. Genome instability and early aging are conditions that arise from mutations in human RecQ helicases. RecQ helicase Sgs1 is missing in yeast cells, making them useful models for comprehending human cell abnormalities and the RecQ helicase function. The RecQ helicase family member, RECQ1,

5076-632: The VP gene encodes the viral protein (VP) that the viral capsid is made of. NS1 contains an HUH superfamily endonuclease domain near its N-terminus , containing both site-specific binding activity and site-specific nicking activity, and a superfamily 3 (SF3) helicase domain toward the C-terminus . 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 frames that encode

5184-586: The XPD helicase that helps form this complex and contributes to its function causes the sensitivity to sunlight seen in all three diseases, as well as the increased risk of cancer seen in XP and premature aging seen in trichothiodystrophy and Cockayne syndrome. XPD helicase mutations leading to trichothiodystrophy are found throughout the protein in various locations involved in protein-protein interactions. This mutation results in an unstable protein due to its inability to form stabilizing interactions with other proteins at

5292-784: The actual process of ATP hydrolysis. Presented with fewer base pairs the duplex then dissociates without further assistance from the enzyme. This mode of unwinding is used by the DEAD/DEAH box helicases . An RNA helicase database is currently available online that contains a comprehensive list of RNA helicases with information such as sequence, structure, and biochemical and cellular functions. Various methods are used to measure helicase activity in vitro . These methods range from assays that are qualitative (assays that usually entail results that do not involve values or measurements) to quantitative (assays with numerical results that can be utilized in statistical and numerical analysis). In 1982–1983,

5400-408: The autosomal recessive diseases Bloom syndrome (BS), Rothmund–Thomson syndrome (RTS), and Werner syndrome (WS), respectively. Bloom syndrome is characterized by a predisposition to cancer with early onset, with a mean age-of-onset of 24 years. Cells of Bloom syndrome patients show a high frequency of reciprocal exchange between sister chromatids (SCEs) and excessive chromosomal damage. There

5508-557: The behaviour of their insect hosts to their own advantage. A baculovirus of the gypsy moth ( Lymantria dispar ) makes their caterpillars climb to the tops of trees where they die. In doing so, they release a shower of millions of progeny viruses that go on to infect more caterpillars. Helicase The human genome codes for 95 non-redundant helicases: 64 RNA helicases and 31 DNA helicases. Many cellular processes, such as DNA replication , transcription , translation , recombination , DNA repair , and ribosome biogenesis involve

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5616-422: 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 via necrosis or apoptosis , which releases virions to

5724-477: The cells of Rothmund-Thomson syndrome patients. RecQ is a family of DNA helicase enzymes that are found in various organisms including bacteria, archaea, and eukaryotes (like humans). These enzymes play important roles in DNA metabolism during DNA replication, recombination, and repair. There are five known RecQ helicase proteins in humans: RecQ1, BLM, WRN, RecQ4, and RecQ5. Mutations in some of these genes are associated with genetic disorders. For instance, mutations in

5832-524: The coding portion of the genome, which is connected to the 5′-end of the 5′ hairpin. Messenger RNA (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 may be used to translate different gene products. Parvoviruses replicate their genome via rolling hairpin replication ,

5940-402: The complementary base pairs, allowing the DNA strands to separate. This creates a replication fork, which serves as a template for synthesizing new DNA strands. Helicase is an essential component of cellular mechanisms that ensures accurate DNA replication and maintenance of genetic information. DNA helicase catalyzes regression. RecG and the enzyme PriA work together to rewind duplex DNA, creating

6048-480: 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

6156-784: The disease were recorded among the seal populations of Lake Baikal and along the shores of the Baltic and North Sea. The infection resembled canine distemper; the animals died within two weeks of respiratory distress and many aborted pups were seen. Many other viruses, including caliciviruses , herpesviruses , adenoviruses and parvoviruses , circulate in marine mammal populations. Fish too have their viruses. They are particularly prone to infections with rhabdoviruses, which are distinct from, but related to rabies virus. At least nine types of rhabdovirus cause economically important diseases in species including salmon, pike, perch, sea bass, carp and cod. The symptoms include anaemia, bleeding, lethargy and

6264-515: The duplex with a directionality and processivity specific to each particular enzyme. Helicases adopt different structures and oligomerization states. Whereas DnaB -like helicases unwind DNA as ring-shaped hexamers , other enzymes have been shown to be active as monomers or dimers . Studies have shown that helicases may act passively, waiting for uncatalyzed unwinding to take place and then translocating between displaced strands, or can play an active role in catalyzing strand separation using

6372-405: 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,

6480-472: The energy generated in ATP hydrolysis. In the latter case, the helicase acts comparably to an active motor, unwinding and translocating along its substrate as a direct result of its ATPase activity. Helicases may process much faster in vivo than in vitro due to the presence of accessory proteins that aid in the destabilization of the fork junction. Enzymatic helicase action, such as unwinding nucleic acids

6588-485: The establishment of a new subfamily, Hamaparvovirinae . Parvoviruses take their name from Latin 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 word piccolo , meaning small , and

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6696-449: 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 , which also includes papillomaviruses , polyomaviruses , and bidnaviruses. Cossaviricota is included in the kingdom Shotokuvirae , which is assigned to the realm Monodnaviria . Parvoviridae belongs to Group II: ssDNA viruses in

6804-563: The first direct biochemical assay was developed for measuring helicase activity. This method was called a "strand displacement assay". Other methods were later developed that incorporated some, if not all of the following: high-throughput mechanics, the use of non-radioactive nucleotide labeling, faster reaction time/less time consumption, real-time monitoring of helicase activity (using kinetic measurement instead of endpoint/single point analysis). These methodologies include: "a rapid quench flow method, fluorescence-based assays, filtration assays,

6912-983: The first viruses to be discovered and characterised, those that cause infections of humans are the most studied. Different viruses can infect all the organs and tissues of the body and the outcomes range from mild or no symptoms, to life-threatening diseases. Humans cannot be infected by plant or insect viruses, but they are susceptible to infections with viruses from other vertebrates. These are called viral zoonoses or zoonotic infections . Examples include, rabies , yellow fever and pappataci fever . The viruses that infect other vertebrates are related to those of humans and most families of viruses that cause human diseases are represented. They are important pathogens of livestock and cause diseases such as foot-and-mouth disease and bluetongue . Jersey and Guernsey breeds of cattle are particularly susceptible to pox viruses , with symptoms characterised by widespread, unsightly skin lesions. And most people have heard of myxomatosis , which

7020-407: The genome and suppress inappropriate recombination. Deficiencies and/or mutations in RecQ family helicases display aberrant genetic recombination and/or DNA replication, which leads to chromosomal instability and an overall decreased ability to proliferate. Mutations in RecQ family helicases BLM, RECQL4 , and WRN, which play a role in regulating homologous recombination, have been shown to result in

7128-415: The genome enclosed in an icosahedral capsid that has a rugged surface. Parvoviruses enter a host cell by endocytosis , 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 (mRNA) is then transcribed and translated , resulting in NS1 initiating replication. During replication,

7236-423: 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

7344-498: 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 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 or lysis . Parvoviruses are believed to be descended from ssDNA viruses that have circular genomes that form

7452-466: The helicase superfamilies except for SF6. All the eukaryotic RNA helicases that have been identified up to date are non-ring forming and are part of SF1 and SF2. On the other hand, ring-forming RNA helicases have been found in bacteria and viruses. However, not all RNA helicases exhibit helicase activity as defined by enzymatic function, i.e., proteins of the Swi/Snf family. Although these proteins carry

7560-438: The honey bee has been important to human societies for centuries. Like all invertebrates , the honey bee ( Apis mellifera) is susceptible to many viral infections, and their numbers have dramatically declined around the world. These bees often suffer infestations of varroa mites , which are vectors for deformed wing virus , as a result, this virus has become one of the most widely distributed and contagious insect viruses on

7668-405: 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 or a herpesvirus , since coinfection alters the cellular environment to allow for replication. In the absence of coinfection, AAV's genome is integrated into

7776-426: 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 uses the 3′-end of the 3′ hairpin as a primer to synthesize a complementary DNA strand for

7884-733: The lanthanide signal, causing a detectable increase in fluorescence that is representative of the amount of unwound DNA and can be used as a quantifiable measurement of helicase activity. The execution and use of single-molecule fluorescence imaging techniques, focusing on methods that include optical trapping in conjunction with epifluorescent imaging, and also surface immobilization in conjunction with total internal reflection fluorescence visualization. Combined with microchannel flow cells and microfluidic control, allow individual fluorescently labeled protein and DNA molecules to be imaged and tracked, affording measurement of DNA unwinding and translocation at single-molecule resolution. Helicase polarity, which

7992-499: 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

8100-469: The lymphocyte-based adaptive immune system that is central to vertebrate immunity, but they are capable of effective immune responses. Phagocytosis was first observed in invertebrates, and this and other innate immune responses are important in immunity to viruses and other pathogens. The hemolymph of invertebrates contains many soluble defence molecules, such as hemocyanins, lectins, and proteins, which protect these animals against invaders. The health of

8208-586: The mediation of antiviral immune response because they can identify foreign RNAs in vertebrates. About 80% of all viruses are RNA viruses and they contain their own RNA helicases. Defective RNA helicases have been linked to cancers, infectious diseases and neuro-degenerative disorders. Some neurological disorders associated with defective RNA helicases are: amyotrophic lateral sclerosis , spinal muscular atrophy , spinocerebellar ataxia type-2 , Alzheimer disease , and lethal congenital contracture syndrome . RNA helicases and DNA helicases can be found together in all

8316-494: 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 , a closely related virus, likewise causes severe illness in cats along with panleukopenia . In pigs, porcine parvovirus is a major cause of infertility as infection frequently leads to death of the fetus. Adeno-associated viruses have become an important vector for gene therapy aimed at treating genetic diseases, such as those caused by

8424-447: The most prominent parvoviruses that cause disease are parvovirus B19 and human bocavirus 1 . B19 infection is often asymptomatic but can manifest in a variety of ways, including Fifth disease with its characteristic rash in children, persistent anemia in immunocompromised persons and in people who have underlying hemoglobinopathies , transient aplastic crises , hydrops fetalis in pregnant women, and arthropathy . Human bocavirus 1

8532-798: The mutation of ATRX gene causes the downregulation of gene expression, such as the alpha-globin genes. It is still unknown what causes the expression of the various characteristics of ATR-X in different patients. XPD (Xeroderma pigmentosum factor D, also known as protein ERCC2) is a 5'-3', Superfamily II, ATP-dependent helicase containing iron-sulphur cluster domains. Inherited point mutations in XPD helicase have been shown to be associated with accelerated aging disorders such as Cockayne syndrome (CS) and trichothiodystrophy (TTD). Cockayne syndrome and trichothiodystrophy are both developmental disorders involving sensitivity to UV light and premature aging, and Cockayne syndrome exhibits severe mental retardation from

8640-433: 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

8748-411: 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 stage, called S-phase, so they must wait in the nucleus until

8856-454: The nucleus. 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 , 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

8964-468: 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

9072-432: The outside of the cell. 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 , 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

9180-458: The passive helicases are conceptualized as Brownian ratchets, driven by thermal fluctuations and subsequent anisotropic gradients across the DNA lattice. The active helicases, in contrast, are conceptualized as stepping motors – also known as powerstroke motors – utilizing either a conformational "inch worm" or a hand-over-hand "walking" mechanism to progress. Depending upon the organism, such helix-traversing progress can occur at rotational speeds in

9288-432: The planet. The virus causes stunted wings and as a result, the infected bees are unable to leave the hive and forage for nectar. Symptomatic bees have a severely reduced life-span of less than 48 hours and are often expelled from the hive by other bees. Bees are crucial to the survival of humans, along with producing honey, they pollinate plants that contribute up to one third of the food we eat, and their dramatic decline

9396-406: The points of mutations. This, in turn, destabilizes the entire TFIIH complex, which leads to defects with transcription and repair mechanisms of the cell. It has been suggested that XPD helicase mutations leading to Cockayne syndrome could be the result of mutations within XPD, causing rigidity of the protein and subsequent inability to switch from repair functions to transcription functions due to

9504-673: The process of synthesis-dependent strand annealing . In the plant Arabidopsis thaliana , FANCM helicase promotes NCO and antagonizes the formation of CO recombinants. Another helicase, RECQ4A/B, also independently reduces COs. It was suggested that COs are restricted because of the long term costs of CO recombination, that is, the breaking up of favourable genetic combinations of alleles built up by past natural selection . RNA helicases are essential for most processes of RNA metabolism such as ribosome biogenesis, pre-mRNA splicing, and translation initiation. They also play an important role in sensing viral RNAs. RNA helicases are involved in

9612-697: The range of 5,000 to 10,000 R.P.M. DNA helicases were discovered in E. coli in 1976. This helicase was described as a "DNA unwinding enzyme" that is "found to denature DNA duplexes in an ATP-dependent reaction, without detectably degrading". The first eukaryotic DNA helicase discovered was in 1978 in the lily plant. Since then, DNA helicases were discovered and isolated in other bacteria, viruses, yeast, flies, and higher eukaryotes. To date, at least 14 different helicases have been isolated from single celled organisms, 6 helicases from bacteriophages, 12 from viruses, 15 from yeast, 8 from plants, 11 from calf thymus, and approximately 25 helicases from human cells. Below

9720-452: The rate at which cancer cells divide, as well as, the efficiency of transactions and cellular homeostasis. Small-molecule-induced entrapment of DNA helicases, a type of DNA metabolic protein, may have deleterious consequences on rapidly proliferating cancer cells, which could be effective in cancer treatment. During meiosis DNA double-strand breaks and other DNA damages in a chromatid are repaired by homologous recombination using either

9828-505: The replication fork to promote unwinding. Active helicases show similar behaviour when acting on both double-strand nucleic acids, dsNA, or ssNA, in regards to the rates of unwinding and rates of translocation, where in both systems V un {\displaystyle V_{\text{un}}} and V trans {\displaystyle V_{\text{trans}}} are approximately equal. These two categories of helicases may also be modeled as mechanisms. In such models,

9936-423: The replication fork, and destabilization forces. The size of the activation barrier to overcome by the helicase contributes to its classification as an active or passive helicase. In passive helicases, a significant activation barrier exists (defined as B > k B T {\displaystyle B>k_{\text{B}}T} , where k B {\displaystyle k_{\text{B}}}

10044-889: 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) caused by parvovirus B19, and viricetes , the suffix used for virus classes. 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. The viruses of vertebrates are informally distinguished between those that primarily cause infections of humans and those that infect other animals. The two fields of study are called medical (or clinical) virology and veterinary virology respectively. Although not

10152-414: The separation of nucleic acid strands that necessitates the use of helicases. Some specialized helicases are also involved in sensing of viral nucleic acids during infection and fulfill an immunological function. A helicase is an enzyme that plays a crucial role in the DNA replication and repair processes. Its primary function is to unwind the double-stranded DNA molecule by breaking the hydrogen bonds between

10260-517: The site of ATP or DNA binding. This results in a structurally functional helicase able to facilitate transcription, however it inhibits its function in unwinding DNA and DNA repair. The lack of a cell's ability to repair mutations, such as those caused by sun damage, is the cause of the high cancer rate in xeroderma pigmentosa patients. RecQ helicases (3'-5') belong to the Superfamily II group of helicases, which help to maintain stability of

10368-490: 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

10476-422: The system lacks a significant barrier, as the helicase can destabilize the nucleic acids, unwinding the double-helix at a constant rate, regardless of the nucleic acid sequence. In active helicases, V un {\displaystyle V_{\text{un}}} is closer to V trans {\displaystyle V_{\text{trans}}} , due to the active helicase ability to directly destabilize

10584-474: 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

10692-562: The time of birth. The XPD helicase mutation has also been implicated in xeroderma pigmentosum (XP), a disorder characterized by sensitivity to UV light and resulting in a several 1000-fold increase in the development of skin cancer. XPD is an essential component of the TFIIH complex, a transcription and repair factor in the cell. As part of this complex, it facilitates nucleotide excision repair by unwinding DNA. TFIIH assists in repairing damaged DNA such as sun damage. A mutation in

10800-402: The typical helicase motifs, hydrolize ATP in a nucleic acid-dependent manner, and are built around a helicase core, in general, no unwinding activity is observed. RNA helicases that do exhibit unwinding activity have been characterized by at least two different mechanisms: canonical duplex unwinding and local strand separation. Canonical duplex unwinding is the stepwise directional separation of

10908-577: The unwinding rate. In passive systems, the rate of unwinding ( V u n {\displaystyle V_{un}} ) is less than the rate of translocation ( V t r a n s {\displaystyle V_{trans}} ) (translocation along the single-strand nucleic acid, ssNA), due to its reliance on the transient unraveling of the base pairs at the replication fork to determine its rate of unwinding. In active helicases, B < k B T {\displaystyle B<k_{\text{B}}T} , where

11016-444: The virus and the population of rabbits increased, but never to the vast numbers seen before 1950. Companion animals such as cats, dogs, and horses, if not vaccinated, can catch serious viral infections. Canine parvovirus 2 is caused by a small DNA virus, and infections are often fatal in pups. The emergence of the parvovirus in the 1970s was the most significant in the history of infectious diseases. The disease spread rapidly across

11124-815: The wedge domain of RecG's association with the SSB linker. In a regression reaction facilitated by RecG and ATPHollidayjunctions are created for later processing. Helicases are often used to separate strands of a DNA double helix or a self-annealed RNA molecule using the energy from ATP hydrolysis, a process characterized by the breaking of hydrogen bonds between annealed nucleotide bases . They also function to remove nucleic acid-associated proteins and catalyze homologous DNA recombination . Metabolic processes of RNA such as translation, transcription, ribosome biogenesis , RNA splicing , RNA transport, RNA editing , and RNA degradation are all facilitated by helicases. Helicases move incrementally along one nucleic acid strand of

11232-483: The world, and thousands of dogs died from the infection. The virus originated in cats, the vector of feline panleukopenia , but a mutation that changed just two amino acids in the viral capsid protein VP2 allowed it to cross the species barrier, and dogs, unlike cats, had no resistance to the disease. Canine distemper virus is closely related to measles virus and is the most important viral disease of dogs. The disease (which

11340-772: The zinc finger and helicase domains. Mutations of ATRX can result in X-linked-alpha-thalassaemia-mental retardation ( ATR-X syndrome ). Various types of mutations found in ATRX have been found to be associated with ATR-X, including most commonly single-base missense mutations, as well as nonsense, frameshift, and deletion mutations. Characteristics of ATR-X include: microcephaly, skeletal and facial abnormalities, mental retardation, genital abnormalities, seizures, limited language use and ability, and alpha-thalassemia. The phenotype seen in ATR-X suggests that

11448-460: Was discovered over 40 years ago by Stollar and Thomas. It was isolated from an Aedes aegypti cell culture where a large number of syncytia were observed and the virus was named cell fusing agent virus (CFAV). Further, when inoculated on different vertebrate cell lines no cytopathic effect (CPE) could be observed and the virus could not be re-isolated, suggesting that the virus must be insect-specific. Invertebrates do not produce antibodies by

11556-508: Was first described in 1760, by Edward Jenner , the pioneer of smallpox vaccination , is highly contagious, but is well controlled by vaccination. In the 1990s, thousands of African lions died from the infection, which they contracted from feral dogs and hyenas. Marine mammals are susceptible to viral infections. In 1988 and 2002, thousands of harbor seals were killed in Europe by the measles-like phocine distemper virus . Large outbreaks of

11664-539: 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 (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

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