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80-522: Simian vacuolating virus 40, SV40 SV40 is an abbreviation for simian vacuolating virus 40 or simian virus 40 , a polyomavirus that is found in both monkeys and humans . Like other polyomaviruses, SV40 is a DNA virus that sometimes causes tumors in animals, but most often persists as a latent infection. SV40 has been widely studied as a model eukaryotic virus, leading to many early discoveries in eukaryotic DNA replication and transcription . Following contamination of polio vaccine batches in

160-523: A demyelinating disease similar to progressive multifocal leukoencephalopathy . In other species, particularly hamsters , SV40 causes a variety of tumors, generally sarcomas. In rats, the oncogenic SV40 large T antigen was used to establish a brain tumor model for primitive neuroectodermal tumor and medulloblastoma . The molecular mechanisms by which the virus reproduces and alters cell function were previously unknown, and research into SV40 vastly increased biologists' understanding of gene expression and

240-457: A host cell . Cellular receptors for polyomaviruses are sialic acid residues of glycans , commonly gangliosides . The attachment of polyomaviruses to host cells is mediated by the binding of VP1 to sialylated glycans on the cell surface. In some particular viruses, additional cell-surface interactions occur; for example, the JC virus is believed to require interaction with the 5HT2A receptor and

320-512: A viral vector for gene therapy . In these helper dependent virus or packaging cell line assisted produced vectors the SV40 large T antigen and SV40 small T antigen are removed. SV40 consists of an unenveloped icosahedral virion with a closed circular double-stranded DNA genome of 5.2 kb. The virion adheres to cell surface receptors of MHC class I by the virion glycoprotein VP1. Penetration into

400-539: A viroporin facilitiating release of viral particles and resulting in cytolysis ; however the presence and role of VP4 have been disputed. SV40 is capable of multiplicity reactivation (MR). MR is the process by which two or more virus genomes containing otherwise lethal damage interact within an infected cell to form a viable virus genome. Yamamato and Shimojo observed MR when SV40 virions were irradiated with UV light and allowed to undergo multiple infection of host cells. Hall studied MR when SV 40 virions were exposed to

480-519: A benefit to pathogenic bacteria by allowing repair of DNA damage, particularly damages that occur in the inflammatory, oxidizing environment associated with infection of a host. When two or more viruses, each containing lethal genomic damages, infect the same host cell, the virus genomes can often pair with each other and undergo HRR to produce viable progeny. This process, referred to as multiplicity reactivation, has been studied in lambda and T4 bacteriophages , as well as in several pathogenic viruses. In

560-449: A chromosome if they know the frequency of the crossovers. Geneticists can also use this method to infer the presence of certain genes. Genes that typically stay together during recombination are said to be linked . One gene in a linked pair can sometimes be used as a marker to deduce the presence of the other gene. This is typically used to detect the presence of a disease-causing gene. The recombination frequency between two loci observed

640-492: A cross-reactive antibody to SV40 T antigen (commonly Pab419) is used to stain tissues directly for the presence of JC virus T antigen. PCR can be used on a biopsy of the tissue or cerebrospinal fluid to amplify the polyomavirus DNA. This allows not only the detection of polyomavirus but also which sub type it is. There are three main diagnostic techniques used for the diagnosis of the reactivation of polyomavirus in polyomavirus nephropathy (PVN): urine cytology, quantification of

720-478: A form of recombination. Recombination also occurs in the reoviridae (dsRNA)(e.g. reovirus), orthomyxoviridae ((-)ssRNA)(e.g. influenza virus ) and coronaviridae ((+)ssRNA) (e.g. SARS ). Recombination in RNA viruses appears to be an adaptation for coping with genome damage. Switching between template strands during genome replication, referred to as copy-choice recombination, was originally proposed to explain

800-477: A lesser extent. Most of these viruses are very common and typically asymptomatic in most human populations studied. BK virus is associated with nephropathy in renal transplant and non-renal solid organ transplant patients, JC virus with progressive multifocal leukoencephalopathy , and Merkel cell virus with Merkel cell cancer . Polyomaviruses are non-enveloped double-stranded DNA viruses with circular genomes of around 5000 base pairs . With such

880-438: A primary transcript that is 3' polyadenylated and 5' capped. SV40 is dormant and is asymptomatic in rhesus monkeys . The virus has been found in many macaque populations in the wild, where it rarely causes disease. However, in monkeys that are immunodeficient —due to, for example, infection with simian immunodeficiency virus —SV40 acts much like the human JC and BK polyomaviruses, producing kidney disease and sometimes

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960-472: A promising genetic marker for human evolution and migration. It is carried by 70–90 percent of humans and is usually transmitted from parents to offspring. This method does not appear to be reliable for tracing the recent African origin of modern humans . Murine polyomavirus was the first polyomavirus discovered, having been reported by Ludwik Gross in 1953 as an extract of mouse leukemias capable of inducing parotid gland tumors. The causative agent

1040-423: A small size, they are ranked among the smallest known double stranded DNA viruses. The genome is packaged in a viral capsid of about 40-50 nanometers in diameter, which is icosahedral in shape (T=7 symmetry). The capsid is composed of 72 pentameric capsomeres of a protein called VP1 , which is capable of self-assembly into a closed icosahedron; each pentamer of VP1 is associated with one molecule of one of

1120-708: A unique domain, called the LT-stabilization domain (LSD), that binds to and inhibits the FBXW7 E3 ligase regulating both cellular and viral oncoproteins. Unlike for SV40, the MCV small T antigen directly transforms rodent cells in vitro. The middle tumor antigen is used in model organisms developed to study cancer, such as the MMTV-PyMT system where middle T is coupled to the MMTV promoter . There it functions as an oncogene , while

1200-542: A variety of exogenous agents (e.g. UV light , X-rays , chemical cross-linking agents) can be repaired by homologous recombinational repair (HRR). These findings suggest that DNA damages arising from natural processes , such as exposure to reactive oxygen species that are byproducts of normal metabolism, are also repaired by HRR. In humans, deficiencies in the gene products necessary for HRR during meiosis likely cause infertility In humans, deficiencies in gene products necessary for HRR, such as BRCA1 and BRCA2 , increase

1280-454: Is a common form of sexual interaction that provides the advantage of recombinational repair of genome damages. The early promoter for SV40 contains three elements. The TATA box is located approximately 20 base-pairs upstream from the transcriptional start site. The 21 base-pair repeats contain six GC boxes and are the site that determines the direction of transcription. Also, the 72 base-pair repeats are transcriptional enhancers . When

1360-596: Is a small probability of recombination at any location along a chromosome, the frequency of recombination between two locations depends on the distance separating them. Therefore, for genes sufficiently distant on the same chromosome, the amount of crossover is high enough to destroy the correlation between alleles. Tracking the movement of genes resulting from crossovers has proven quite useful to geneticists. Because two genes that are close together are less likely to become separated than genes that are farther apart, geneticists can deduce roughly how far apart two genes are on

1440-411: Is a type of site-specific genetic recombination that helps immune cells rapidly diversify to recognize and adapt to new pathogens . During meiosis, synapsis (the pairing of homologous chromosomes) ordinarily precedes genetic recombination. Genetic recombination is catalyzed by many different enzymes . Recombinases are key enzymes that catalyse the strand transfer step during recombination. RecA ,

1520-446: Is also measure by PCR. Tissue staining using a monoclonal antibody against MCV T antigen shows utility in differentiating Merkel cell carcinoma from other small, round cell tumors. Blood tests to detect MCV antibodies have been developed and show that infection with the virus is widespread although Merkel cell carcinoma patients have exceptionally higher antibody responses than asymptomatically infected persons. The JC virus offers

1600-461: Is altered. Gene conversion has often been studied in fungal crosses where the 4 products of individual meioses can be conveniently observed. Gene conversion events can be distinguished as deviations in an individual meiosis from the normal 2:2 segregation pattern (e.g. a 3:1 pattern). Recombination can occur between DNA sequences that contain no sequence homology . This can cause chromosomal translocations , sometimes leading to cancer. B cells of

1680-555: Is called recombinant DNA . A prime example of such a use of genetic recombination is gene targeting , which can be used to add, delete or otherwise change an organism's genes. This technique is important to biomedical researchers as it allows them to study the effects of specific genes. Techniques based on genetic recombination are also applied in protein engineering to develop new proteins of biological interest. Examples include Restriction enzyme mediated integration , Gibson assembly and Golden Gate Cloning . DNA damages caused by

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1760-542: Is copied from one chromosome to another, without the donating chromosome being changed) (see SDSA – Synthesis Dependent Strand Annealing pathway in Figure); or by the breaking and rejoining of DNA strands, which forms new molecules of DNA (see DHJ pathway in Figure). Recombination may also occur during mitosis in eukaryotes where it ordinarily involves the two sister chromosomes formed after chromosomal replication. In this case, new combinations of alleles are not produced since

1840-515: Is distantly related to MCV. Two viruses—HPyV6 and HPyV7—are most closely related to KI and WU viruses, while HPyV9 is most closely related to the African green monkey-derived lymphotropic polyomavirus (LPV). A fourteenth virus has been described. Lyon IARC polyomavirus is related to raccoon polyomavirus. The following 14 polyomaviruses with human hosts had been identified and had their genomes sequenced as of 2017: Deltapolyomavirus contains only

1920-497: Is extremely efficient at inducing cellular transformation ; SV40 has an additional capsid protein VP4; some examples have an additional regulatory protein called agnoprotein expressed from the late region. The genome also contains a non-coding control or regulatory region containing the early and late regions' promoters , transcriptional start sites, and the origin of replication . The polyomavirus life cycle begins with entry into

2000-547: Is often confounded by high levels of cross-reactivity for SV40 with widespread human polyomaviruses. Most virologists dismiss SV40 as a cause for human cancers. The diagnosis of polyomavirus almost always occurs after the primary infection as it is either asymptomatic or sub-clinical. Antibody assays are commonly used to detect presence of antibodies against individual viruses. Competition assays are frequently needed to distinguish among highly similar polyomaviruses. In cases of progressive multifocal leucoencephalopathy (PML),

2080-406: Is the crossing-over value . It is the frequency of crossing over between two linked gene loci ( markers ), and depends on the distance between the genetic loci observed. For any fixed set of genetic and environmental conditions, recombination in a particular region of a linkage structure ( chromosome ) tends to be constant, and the same is then true for the crossing-over value which is used in

2160-601: Is well documented in male Drosophila melanogaster . The "Haldane-Huxley rule" states that achiasmy usually occurs in the heterogametic sex . Heterochiasmy occurs when recombination rates differ between the sexes of a species. In humans, each oocyte has on average 41.6 ± 11.3 recombinations, 1.63-fold higher than sperms. This sexual dimorphic pattern in recombination rate has been observed in many species. In mammals, females most often have higher rates of recombination. Numerous RNA viruses are capable of genetic recombination when at least two viral genomes are present in

2240-859: The Diamond Princess cruise, two mutations, 29736G > T and 29751G > T (G13 and G28) were located in Coronavirus 3′ stem-loop II-like motif (s2m) of SARS-CoV-2. Although s2m is considered an RNA motif highly conserved in 3' untranslated region among many coronavirus species, this result also suggests that s2m of SARS-CoV-2 is RNA recombination /mutation hotspot. SARS-CoV-2's entire receptor binding motif appeared, based on preliminary observations, to have been introduced through recombination from coronaviruses of pangolins . However, more comprehensive analyses later refuted this suggestion and showed that SARS-CoV-2 likely evolved solely within bats and with little or no recombination. Nowak and Ohtsuki noted that

2320-488: The Merkel cell virus with heparan sulfate . However, in general virus-cell interactions are mediated by commonly occurring molecules on the cell surface, and therefore are likely not a major contributor to individual viruses' observed cell-type tropism . After binding to molecules on the cell surface, the virion is endocytosed and enters the endoplasmic reticulum - a behavior unique among known non-enveloped viruses - where

2400-509: The SP1 protein interacts with the 21 base-pair repeats, it binds either the first or the last three GC boxes. Binding the first three initiates early expression , binding the last three initiates late expression. The function of the 72 base-pair repeats is to enhance the amount of stable RNA and increase the rate of synthesis. This is done by binding ( dimerization ) with the AP-1 transcription factor to give

2480-585: The University of Ghent ( Belgium ). SV40 has become a totemic subject among anti-vaccination activists, where its presence in contaminated vaccine is accused of being a cause of a cancer "epidemic" and of being responsible for HIV/AIDS . Polyomavirus Polyomaviridae is a family of viruses whose natural hosts are primarily mammals and birds. As of 2024, there are eight recognized genera. 14 species are known to infect humans, while others, such as Simian Virus 40 , have been identified in humans to

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2560-416: The black sea bass and gilthead seabream . A total of fourteen polyomaviruses are known to infect humans. Multiplicity reactivation During meiosis in eukaryotes , genetic recombination involves the pairing of homologous chromosomes . This may be followed by information transfer between the chromosomes. The information transfer may occur without physical exchange (a section of genetic material

2640-560: The genomes of an asexual population tend to accumulate more deleterious mutations over time than beneficial or reversing mutations. Chromosomal crossover involves recombination between the paired chromosomes inherited from each of one's parents, generally occurring during meiosis . During prophase I (pachytene stage) the four available chromatids are in tight formation with one another. While in this formation, homologous sites on two chromatids can closely pair with one another, and may exchange genetic information. Because there

2720-420: The immune system perform genetic recombination, called immunoglobulin class switching . It is a biological mechanism that changes an antibody from one class to another, for example, from an isotype called IgM to an isotype called IgG . In genetic engineering , recombination can also refer to artificial and deliberate recombination of disparate pieces of DNA, often from different organisms, creating what

2800-487: The origin of replication . Early transcription gives two spliced RNAs that are both 19s. Late transcription gives both a longer 16s, which synthesizes the major viral capsid protein VP1; and the smaller 19s, which gives VP2 and VP3 through leaky scanning . All of the proteins, besides the 5% of large T, return to the nucleus because assembly of the viral particle happens there. A putative late protein VP4 has been reported to act as

2880-508: The poliovirus RNA-dependent RNA polymerase (RdRp) is able to carry out recombination. Recombination appears to occur by a copy choice mechanism in which the RdRp switches (+)ssRNA templates during negative strand synthesis. Recombination by RdRp strand switching also occurs in the (+)ssRNA plant carmoviruses and tombusviruses . Recombination appears to be a major driving force in determining genetic variability within coronaviruses, as well as

2960-430: The 1950s and 1960s, SV40 came under suspicion as a possible cancer risk, but no subsequent increased cancer rate was observed, making such a risk unlikely. Nevertheless SV40 has become a cause célèbre for anti-vaccination activists, who have blamed it for multiple ills, including cancer and HIV/AIDS . The hypothesis that SV40 might cause cancer in humans was a particularly controversial area of research, fuelled by

3040-584: The DNA crosslinking agent 4, 5', 8-trimethylpsoralen. Under conditions in which only a single virus particle entered each host cell, approximately one DNA cross-link was lethal to the virus and could not be repaired. In contrast, when multiple viral genomes infected a host cell, psoralen -induced DNA cross-links were repaired; that is, MR occurred. Hall suggested that the virions with cross-linked DNA were repaired by recombinational repair. Michod et al. reviewed numerous examples of MR in different viruses and suggested that MR

3120-559: The SV40 clade, the avian clade, and the murine polyomavirus clade. A subsequent proposed reclassification by the International Committee on Taxonomy of Viruses (ICTV) recommended dividing the family of Polyomaviridae into three genera: The current ICTV classification system recognises six genera and 117 species, of which five could not be assigned a genus. This system retains the distinction between avian and mammalian viruses, grouping

3200-527: The US between 1955 and 1961 were found to be contaminated with SV40, from the growth medium and from the original seed strain. Population level studies did not show extensive evidence of increase in cancer incidence as a result of exposure, though SV40 has been extensively studied. A thirty-five year follow-up did not find excess numbers of cancers associated with SV40. Due to its high tissue tropism , biotechnology companies seek to utilize modified SV40 based vectors as

3280-512: The ability of coronavirus species to jump from one host to another and, infrequently, for the emergence of novel species, although the mechanism of recombination in is unclear. In early 2020, many genomic sequences of Australian SARS‐CoV‐2 isolates have deletions or mutations (29742G>A or 29742G>U; "G19A" or "G19U") in the s2m, suggesting that RNA recombination may have occurred in this RNA element. 29742G("G19"), 29744G("G21"), and 29751G("G28") were predicted as recombination hotspots. During

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3360-403: The arms of the chromosomes flanking the recombination event remain in the parental configuration. Thus, explanations for the adaptive function of meiosis that focus exclusively on crossing-over are inadequate to explain the majority of recombination events. Achiasmy is the phenomenon where autosomal recombination is completely absent in one sex of a species. Achiasmatic chromosomal segregation

3440-413: The avian subset into the genus Gammapolyomavirus . The six genera are: The following species are unassigned to a genus: Description of additional viruses is ongoing. These include the sea otter polyomavirus 1 and Alpaca polyomavirus Another virus is the giant panda polyomavirus 1. Another virus has been described from sigmodontine rodents. Another - tree shrew polyomavirus 1 - has been described in

3520-701: The bacterial RecA protein is RadA. Bacteria regularly undergo genetic recombination in three main ways: Sometimes a strand of DNA is transferred into the target cell but fails to be copied as the target divides. This is called an abortive transfer . In eukaryotes , recombination during meiosis is facilitated by chromosomal crossover . The crossover process leads to offspring having different combinations of genes from those of their parents, and can occasionally produce new chimeric alleles . The shuffling of genes brought about by genetic recombination produces increased genetic variation . It also allows sexually reproducing organisms to avoid Muller's ratchet , in which

3600-400: The case of pathogenic viruses, multiplicity reactivation may be an adaptive benefit to the virus since it allows the repair of DNA damages caused by exposure to the oxidizing environment produced during host infection. See also reassortment . A molecular model for the mechanism of meiotic recombination presented by Anderson and Sekelsky is outlined in the first figure in this article. Two of

3680-497: The cell cycle is a powerful force for oncogenic transformation. The small tumor antigen protein is also able to activate several cellular pathways that stimulate cell proliferation. Polyomavirus small T antigens commonly target protein phosphatase 2A ( PP2A ), a key multisubunit regulator of multiple pathways including Akt , the mitogen-activated protein kinase (MAPK) pathway, and the stress-activated protein kinase (SAPK) pathway. Merkel cell polyomavirus small T antigen encodes

3760-605: The cell is through a caveolin vesicle . Inside the cell nucleus , the cellular RNA polymerase II acts to promote early gene expression. This results in an mRNA that is spliced into two segments. The small and large T antigens result from this. The large T antigen has two functions: 5% goes to the plasma cell membrane and 95% returns to the nucleus. Once in the nucleus the large T antigen binds three viral DNA sites, I, II and III. Binding of sites I and II autoregulates early RNA synthesis . Binding to site II takes place in each cell cycle. Binding site I initiates DNA replication at

3840-453: The chief recombinase found in Escherichia coli , is responsible for the repair of DNA double strand breaks (DSBs). In yeast and other eukaryotic organisms there are two recombinases required for repairing DSBs. The RAD51 protein is required for mitotic and meiotic recombination, whereas the DNA repair protein, DMC1 , is specific to meiotic recombination. In the archaea, the ortholog of

3920-504: The early mRNA is reduced and expression of the late mRNA, which encodes the viral capsid proteins, begins. As these interactions begin, the LTs belonging to several polyomaviruses, including Merkel cell polyomavirus , present oncogenic potential. Several mechanisms have been described for regulating the transition from early to late gene expression, including the involvement of the LT protein in repressing

4000-437: The early promoter, the expression of un-terminated late mRNAs with extensions complementary to early mRNA, and the expression of regulatory microRNA . Expression of the late genes results in accumulation of the viral capsid proteins in the host cell cytoplasm. Capsid components enter the nucleus in order to encapsidate new viral genomic DNA. New virions may be assembled in viral factories . The mechanism of viral release from

4080-666: The exact mechanisms are unclear. The polyomaviruses are members of group I (dsDNA viruses). The classification of polyomaviruses has been the subject of several proposed revisions as new members of the group are discovered. Formerly, polyomaviruses and papillomaviruses , which share many structural features but have very different genomic organizations, were classified together in the now-obsolete family Papovaviridae . (The name Papovaviridae derived from three abbreviations: Pa for Papillomavirus , Po for Polyomavirus , and Va for "vacuolating.") The polyomaviruses were divided into three major clades (that is, genetically related groups):

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4160-619: The first months of the COVID-19 pandemic, such a recombination event was suggested to have been a critical step in the evolution of SARS-CoV-2's ability to infect humans. Linkage disequilibrium analysis confirmed that RNA recombination with the 11083G > T mutation also contributed to the increase of mutations among the viral progeny. The findings indicate that the 11083G > T mutation of SARS-CoV-2 spread during Diamond Princess shipboard quarantine and arose through de novo RNA recombination under positive selection pressure. In three patients on

4240-543: The four chromatids present early in meiosis (prophase I) are paired with each other and able to interact. Recombination, in this model, is initiated by a double-strand break (or gap) shown in the DNA molecule (chromatid) at the top of the figure. Other types of DNA damage may also initiate recombination. For instance, an inter-strand cross-link (caused by exposure to a cross-linking agent such as mitomycin C) can be repaired by HRR. Two types of recombinant product are produced. Indicated on

4320-425: The four human viruses shown in the above table. The Alpha and Beta groups contain viruses that infect a variety of mammals. The Gamma group contains the avian viruses. Clinically significant disease associations are shown only where causality is expected. Antibodies to the monkey lymphotropic polyomavirus have been detected in humans suggesting that this virus - or a closely related virus - can infect humans. All

4400-455: The historical contamination of some batches of polio vaccine with SV40 in the 1950s and 1960s. "Persuasive evidence now indicates that SV40 is causing infections in humans today and represents an emerging pathogen." However "It appears unlikely that SV40 infection alone is sufficient to cause human malignancy..." It has been suggested that SV40 may act as a co-carcinogen with crocidolite asbestos to cause mesothelioma . Some vaccines made in

4480-592: The host cell machinery to replicate the host cell needs to be in s-phase for this to begin. Due to this, large T-antigen also modulates cellular signaling pathways to stimulate progression of the cell cycle by binding to a number of cellular control proteins. This is achieved by a two prong attack of inhibiting tumor suppressing genes p53 and members of the retinoblastoma (pRB) family, and stimulating cell growth pathways by binding cellular DNA, ATPase-helicase, DNA polymerase α association, and binding of transcription preinitiation complex factors. This abnormal stimulation of

4560-422: The host cell varies among polyomaviruses; some express proteins that facilitate cell exit, such as the agnoprotein or VP4 . In some cases high levels of encapsidated virus result in cell lysis , releasing the virions. The large tumor antigen plays a key role in regulating the viral life cycle by binding to the viral origin of DNA replication where it promotes DNA synthesis. Also as the polyomavirus relies on

4640-528: The kidneys of monkeys without causing disease, but can cause cancer in rodents under laboratory conditions. In the 1950s and early 1960s, well over 100 million people may have been exposed to SV40 due to previously undetected SV40 contamination of polio vaccine , prompting concern about the possibility that the virus might cause disease in humans. Although it has been reported as present in some human cancers, including brain tumors , bone tumors , mesotheliomas , and non-Hodgkin's lymphomas , accurate detection

4720-406: The late region of the genome. The agnoprotein is a small multifunctional phospho-protein found in the late coding part of the genome of some polyomaviruses, most notably BK virus , JC virus , and SV40 . It is essential for proliferation in the viruses that express it and is thought to be involved in regulating the viral life cycle, particularly replication and viral exit from the host cell, but

4800-429: The low calcium concentration in the cytoplasm. Both expression of viral genes and replication of the viral genome occur in the nucleus using host cell machinery. The early genes - comprising at minimum the small tumor antigen (ST) and large tumor antigen (LT) - are expressed first, from a single alternatively spliced messenger RNA strand. These proteins serve to manipulate the host's cell cycle - dysregulating

4880-420: The origin of life ( abiogenesis ) is also the origin of biological evolution . They pointed out that all known life on earth is based on biopolymers and proposed that any theory for the origin of life must involve biological polymers that act as information carriers and catalysts. Lehman argued that recombination was an evolutionary development as ancient as the origins of life. Smail et al. proposed that in

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4960-437: The other two capsid proteins, VP2 or VP3 . The genome of a typical polyomavirus codes for between 5 and 9 proteins , divided into two transcriptional regions called the early and late regions due to the time during infection in which they are transcribed. Each region is transcribed by the host cell's RNA polymerase II as a single pre-messenger RNA containing multiple genes. The early region usually codes for two proteins,

5040-583: The polyomaviruses are highly common childhood and young adult infections. Most of these infections appear to cause little or no symptoms. These viruses are probably lifelong persistent among almost all adults. Diseases caused by human polyomavirus infections are most common among immunocompromised people; disease associations include BK virus with nephropathy in renal transplant and non-renal solid organ transplant patients, JC virus with progressive multifocal leukoencephalopathy , and Merkel cell virus (MCV) with Merkel cell cancer . SV40 replicates in

5120-626: The positive correlation of recombination events over short distances in organisms with a DNA genome (see first Figure, SDSA pathway). Recombination can occur infrequently between animal viruses of the same species but of divergent lineages. The resulting recombinant viruses may sometimes cause an outbreak of infection in humans. Especially in coronaviruses, recombination may also occur even among distantly related evolutionary groups (subgenera), due to their characteristic transcription mechanism, that involves subgenomic mRNAs that are formed by template switching. When replicating its (+)ssRNA genome ,

5200-460: The process during which homologous sequences are made identical also falls under genetic recombination. Genetic recombination and recombinational DNA repair also occurs in bacteria and archaea , which use asexual reproduction . Recombination can be artificially induced in laboratory ( in vitro ) settings, producing recombinant DNA for purposes including vaccine development. V(D)J recombination in organisms with an adaptive immune system

5280-413: The production of genetic maps . In gene conversion, a section of genetic material is copied from one chromosome to another, without the donating chromosome being changed. Gene conversion occurs at high frequency at the actual site of the recombination event during meiosis . It is a process by which a DNA sequence is copied from one DNA helix (which remains unchanged) to another DNA helix, whose sequence

5360-488: The regulation of cell growth. SV40 was first identified by Ben Sweet and Maurice Hilleman in 1960 when they found that between 10 and 30% of polio vaccines in the US were contaminated with SV40. In 1962, Bernice Eddy described the SV40 oncogenic function inducing sarcoma and ependymomas in hamsters inoculated with monkeys cells infected with SV40. The complete viral genome was sequenced by Weissman at Yale University (US) in 1978 and also by Fiers and his team at

5440-427: The right side is a "crossover" (CO) type, where the flanking regions of the chromosomes are exchanged, and on the left side, a "non-crossover" (NCO) type where the flanking regions are not exchanged. The CO type of recombination involves the intermediate formation of two "Holliday junctions" indicated in the lower right of the figure by two X-shaped structures in each of which there is an exchange of single strands between

5520-426: The risk of cancer (see DNA repair-deficiency disorder ). In bacteria, transformation is a process of gene transfer that ordinarily occurs between individual cells of the same bacterial species. Transformation involves integration of donor DNA into the recipient chromosome by recombination. This process appears to be an adaptation for repairing DNA damages in the recipient chromosome by HRR. Transformation may provide

5600-430: The same host cell. Recombination is largely responsible for RNA virus diversity and immune evasion. RNA recombination appears to be a major driving force in determining genome architecture and the course of viral evolution among picornaviridae ( (+)ssRNA ) (e.g. poliovirus ). In the retroviridae ((+)ssRNA)(e.g. HIV ), damage in the RNA genome appears to be avoided during reverse transcription by strand switching,

5680-488: The sister chromosomes are usually identical. In meiosis and mitosis, recombination occurs between similar molecules of DNA ( homologous sequences ). In meiosis, non-sister homologous chromosomes pair with each other so that recombination characteristically occurs between non-sister homologues. In both meiotic and mitotic cells, recombination between homologous chromosomes is a common mechanism used in DNA repair . Gene conversion –

5760-399: The small and large tumor antigens, produced by alternative splicing . The late region contains the three capsid structural proteins VP1, VP2, and VP3, produced by alternative translational start sites. Additional genes and other variations on this theme are present in some viruses: for example, rodent polyomaviruses have a third protein called middle tumor antigen in the early region, which

5840-569: The tissue where the tumor develops is determined by the MMTV promoter. The polyomavirus capsid consists of one major component, major capsid protein VP1 , and one or two minor components, minor capsid proteins VP2 and VP3 . VP1 pentamers form the closed icosahedral viral capsid , and in the interior of the capsid each pentamer is associated with one molecule of either VP2 or VP3. Some polyomaviruses, such as Merkel cell polyomavirus , do not encode or express VP3. The capsid proteins are expressed from

5920-450: The transition from G1 phase to S phase , when the host cell's genome is replicated - because host cell DNA replication machinery is needed for viral genome replication. The precise mechanism of this dysregulation depends on the virus; for example, SV40 LT can directly bind host cell p53 , but murine polyomavirus LT does not. LT induces DNA replication from the viral genome's non-coding control region (NCCR), after which expression of

6000-431: The tree shrew. Most polyomaviruses do not infect humans. Of the polyomaviruses cataloged as of 2017, a total of 14 were known with human hosts. However, some polyomaviruses are associated with human disease, particularly in immunocompromised individuals. MCV is highly divergent from the other human polyomaviruses and is most closely related to murine polyomavirus. Trichodysplasia spinulosa-associated polyomavirus (TSV)

6080-573: The two participating chromatids. This pathway is labeled in the figure as the DHJ (double-Holliday junction) pathway. The NCO recombinants (illustrated on the left in the figure) are produced by a process referred to as "synthesis dependent strand annealing" (SDSA). Recombination events of the NCO/SDSA type appear to be more common than the CO/DHJ type. The NCO/SDSA pathway contributes little to genetic variation, since

6160-421: The viral capsid structure is likely to be disrupted by action of host cell disulfide isomerase enzymes. The details of transit to the nucleus are not clear and may vary among individual polyomaviruses. It has been frequently reported that an intact, albeit distorted, virion particle is released from the endoplasmic reticulum into the cell cytoplasm, where the genome is released from the capsid, possibly due to

6240-442: The viral load can be done through PCR. This is also true for the blood. Renal biopsy can also be used if the two methods just described are inconclusive or if the specific viral load for the renal tissue is desired. Similarly to the urine cytology, the renal cells are examined under light microscopy for polyomavirus inclusion of the nucleus, as well as cell lysis and viral partials in the extra cellular fluid. The viral load as before

6320-448: The viral load in both urine and blood, and a renal biopsy . The reactivation of polyomavirus in the kidneys and urinary tract causes the shedding of infected cells, virions, and/or viral proteins in the urine. This allows urine cytology to examine these cells, which if there is polyomavirus inclusion of the nucleus, is diagnostic of infection. Also as the urine of an infected individual will contain virions and/or viral DNA, quantitation of

6400-720: Was identified as a virus by Sarah Stewart and Bernice Eddy , after whom it was once called "SE polyoma". The term "polyoma" refers to the viruses' ability to produce multiple (poly-) tumors (-oma) under certain conditions. The name has been criticized as a "meatless linguistic sandwich" ("meatless" because both morphemes in "polyoma" are affixes) giving little insight into the viruses' biology; in fact, subsequent research has found that most polyomaviruses rarely cause clinically significant disease in their host organisms under natural conditions. Dozens of polyomaviruses have been identified and sequenced as of 2017, infecting mainly birds and mammals. Two polyomaviruses are known to infect fish,

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