Simian virus 40 does not induce disease in its natural. Recombinant dna molecules consisting of the simian virus 40 sv40 early region and different subgenomic hepatitis b virus dna fragments were constructed in vitro. In the baculovirus prototype autographa californica multiple nucleopolyhedrovirus acmnpv, the polyhedrin promoter very late promoter transcribes its gene by a viral rna polymerase. This same virus contaminated the polio vaccine administered to. Sv40 is an attractive potential vector with highefficiency gene transfer into a wide variety of human tissues, including the bone marrow, a critical target organ for the cure of many diseases. Subsequently, investigators found sv40 dna in biopsy specimens obtained from patients with cancers such as mesothelioma lung, osteosarcoma bone and nonhodgkins lymphoma lymph nodes. Simian virus 40 sv40 is a nonenveloped, doublestranded dna virus with a 5. The virus was discovered in 1960 in rhesus macaque monkey kidney cells that were used in the production of the original salk and sabin polio vaccines 1.
Generation of a verobased packaging cell line to produce. These findings were supported by the isolation of infectious sv40 from a choroid plexus tumor. Its genome is very small and can be easily modified for gene therapy purpose. Sv40 vector genome used for the production of vector particles and generated a novel verobased packaging cell line named supervero that exclusively expresses the sv40 large t antigen. Sv40 is a wellknown virus, nonreplicative vectors are easytomake, and can be produced in titers of 10 12 iuml. This virus contaminated both the inactivated polio vaccine ipv created by dr. To generate a recombinant sv40 virus with gfp rsvgfp, pegfpn1 clontech was digested using sali and noti, and the gfp gene was cloned at the same restriction sites of psl4pl. Ecotropic generlly means able to infect only cells of species originally isolated from or identified in. The transcription factors are transported into the nucleus by importins and can carry the plasmid construct containing the sv40 nuclear dts sv40dts with them 35. Simian virus 40 sv40 is a monkey virus that was administered to human populations by contaminated vaccines which were produced in sv40 naturally infected monkey cells. The influence of sv40 polya on gene expression of baculovirus. It is strongly recommended you download this document to your own computer and open from there.
One of the primary organs affected by sepsis is the lung, presenting as the acute respiratory distress syndrome ards. Recombinant sv40 vectors rsv40 are good candidates for gene transfer, as they display some unique features. Sv40 was the 40th virus found in rhesus monkey kidney cells when these cells were used to make the polio vaccine. Simian virus 40 and human disease the journal of infectious. Simian virus 40 infection of humans pubmed central pmc. These same tumor types have been found to contain sv40 dna and proteins in humans. Sv40 is an abbreviation for simian vacuolating virus 40 or simian virus 40, a polyomavirus that is found in both monkeys and humans. Some lots of polio vaccines in the 1960s were discovered to contain sv40. The molecular biology of sv40 has led to seminal discoveries in the fields of transcription, dna replication, and oncogenic transformation. Over the last decade, provocative evidence has accumulated that suggests that sv40 may be a human pathogen. Nevertheless, it may be virtually impossible to rule out such connection. Simian virus 40 transformation, malignant mesothelioma and. Welcome to vector database vector database is a digital collection of vector backbones assembled from publications and commercially available sources. In the aftermath of these admissions and inquiries, the cdc launched a fact sheet page on its website addressing the links between cancer, simian virus 40 sv40, and polio vaccine which noted.
Emergent human pathogen simian virus 40 and its role in cancer. Recombinant sv40 vectors rsv40 are good candidates for gene transfer, as they. Simian virus40 sv40, an icosahedral papovavirus, has recently been modified to serve as a gene delivery vector. Pdf expression of hepatitis b antigens with a simian virus. Hundreds of millions of people were immunized with sv40contaminated vaccine, making this by far the largest singlesource. Workshop on simian virus40 sv 40 a possible human polyomavirus. Simian virus 40 sv40 is a dna virus isolated in 1960 from contaminated polio vaccines, that induces mesotheliomas, lymphomas, brain and bone tumors, and sarcomas, including osteosarcomas, in hamsters. Shuttles with the pfbaav backbone can be used for either the triple transfection or baculovirus system. Vaccine contamination with sv40 occurred in the united states between 1955 and 1961 simian vacuolating virus 40, known as sv40, is a virus found in monkeys and humans, which has the potential to cause cancer, mainly in animals, although research indicates that it doesnt cause cancer in humans.
We have described a novel gene transfer system, in which replicationincompetent, t antigendeleted simian virus 40 sv40 is used as the transduction vehicle. Pdf expression of hepatitis b antigens with a simian. Shuttle plasmids are provided free of charge when intended for virus production at the university of iowa viral vector core. Chapter 6 sv40 virus expression vectors sciencedirect.
A novel sv40based vector successfully transduces and. The rationale for this approach was based on several important aspects of sv40 virus and its activity. Recent molecular biology and epidemiological studies suggest that sv40 may be contagiously transmitted in humans by horizontal infection, independently from the earlier. This article is an open access publication abstract there has been a resurgence in gene therapy efforts that is partly fueled by the identi. Simian virus 40 sv40 is a polyomavirus that is found in both monkeys and humans. The following statement is an introduction for a more detailed packet on sv 40 and animal viruses in the production of vaccines. The sv40 origin allows for replication in mammalian cells expressing the sv40 t antigen. Factors influencing the production of recombinant sv40. Supervero cells produce similar numbers of sv40 vector particles compared to the currently used packaging cell lines, albeit. A simian virus known as sv40 has been associated with a number of rare human cancers. Delivery of genes, or other genetic material, by a vector is termed transduction and the infected cells are described as transduced.
Recombinant sv40 vectors rsv40 are good candidates for. Oncolytic herpes simplex virus vector therapy of breast cancer in c31sv40 tantigen transgenic mice renbin liu, susan varghese and samuel d. Simian virus40 as a gene therapy vector request pdf. Like other polyomaviruses, sv40 is a dna virus that has the potential to cause tumors in animals, but most often persists as a latent infection. The resulting plasmids, named prsvluc and prsvgfp, respectively, were verified by restriction analysis.
Thomas robertss lab contains the insert sv40 lt and is published in cancer cell. Sepsisinduced ards was established by cecal ligation double puncture 2clp. Hundreds of millions of people were immunized with sv40 contaminated vaccine, making this by far the largest singlesource. Molecular biologists first harnessed this machinery in the 1970s. Simian virus 40, a polyomavirus found in simians nonhuman primates, sv40 has no relationship to the human immunodeficiency virus hiv or to the simian immunodeficiency virus siv. Polio vaccines used in the late 1950s and early 1960s were contaminated with a virus called simian virus 40 sv40 present in monkey kidney cells used to grow the vaccine.
Sv40 virus expression vectors 115 inhibiting host protein synthesis, s v40 vectors can express an exogenous protein at levels that equal or exceed the production of viral proteins by enveloped viruses such as influenza virus or vesicular stomatitis virus chapter 1, which divert cellular synthesis totally to their own products. The simian virus 40 polyadenylation signal sv40 polya has been routinely inserted downstream of the polyhedrin promoter in many baculovirus expression vector systems bevs. Sv40 is a small 40 nm nonenveloped dna virus in the polyomavirus family imperiale and major, 2007. Simian virus 40 sv40, an icosahedral papovavirus, has recently been modified to serve as a gene delivery vector. This is a free resource for the scientific community that is compiled by addgene this page is informational only this vector is not available from addgene please contact the manufacturer for further details. Recombinant dna molecules consisting of the simian virus 40 sv40 early region and different subgenomic hepatitis b virus dna fragments were constructed in vitro and packaged in vivo into sv40. Sv40 promoter for highlevel constitutive expression of your gene of interest cmv promoter for highlevel constitutive expression of the cycle 3 gfpzeocin fusion sv40 origin for episomal replication and simple vector rescue in cell lines expressing the sv40 large t antigen the ptracercmv2. In addition, the ability of these vectors to infect nondividing cells makes them attractive for ldgt. Sv40 vectors carrying the luciferase reporter gene svluc were administered intratracheally immediately after sepsis induction. Research on sv 40 exposure and the development of cancer. Organ damage in sepsis involves an alteration in gene expression, making gene transfer a potential therapeutic modality. Attempting to open large pdf files over the internet within the browser window may cause problems. Simian virus 40 in humans infectious agents and cancer.
A mutated p53 gene may contribute to uncontrolled cellular proliferation, leading to a tumor. We have described a novel gene transfer system, in which replicationincompetent, t antigendeleted simian virus40 sv40 is used as. Sv40 plasmids vectors can be packaged only if their dna is within the range of 3900 to 5300 bp. Sv40 is believed to suppress the tumorsuppressing p53 in humans. Sv40 vectors have broad specificity, can be produced in high titers, and have high transduction efficiency strayer, 2000.
Sv40 does this with very little molecular machinery. This same virus contaminated the polio vaccine administered to 98 million americans from 1955 to 1963. This is a free resource for the scientific community that is compiled by addgene. In the present study, the three sv40 capsid proteins, vp1, vp2, and vp3, were produced in spodoptera frugiperda sf9 insect cells. During the past 4 years, polymerase chain reaction pcr assays have detected dna sequences related to sv40 an oncogenic simian polyomavirus in a variety of human tissues, especially choroid plexus tumors, ependymomas, mesotheliomas, and osteosarcomas 17. Simian virus 40 sv40 is a virus that infects several species of monkeys and typically does not cause disease in them. Although detection of sv40 dna by pcr for particular cancers e.
Simian virus40 as a gene therapy vector dna and cell biology. The virus was first isolated as a contaminant from a monkey kidney culture used for the production of poliovirus vaccine. Vector database is a digital collection of vector backbones assembled from publications and commercially available sources. Since its discovery, simian virus 40 sv40 has been one of the most intensely studied animal viruses. Simian virus 40 vectors for pulmonary gene therapy. Sv40 contamination of polio vaccine the tissue cultures used to grow poliovirus for the vaccines in question came from kidneys of rhesus and cynomolgus macaques. Recently, the institute of medicine of the national academies concluded that the biological evidence is strong that sv40 is a transforming virus and that the biological evidence is of moderate. Because of crossreactivity between bk, jc, and sv40 antibodies and the lack of standardized serologic assays to identify sv40 specificity of antibodies present in single samples of human serum, it is difficult to determine whether sv40 was present in humans before the population was exposed to sv40 in the early polio and adenovirus vaccines. Adenoassociated virus aav as a vector for gene therapy. Atlanta the us institute of medicine iom is looking into whether polio vaccines contaminated with the simian virus sv40 thought to inactivate p53 and rb and given 40 years ago have caused a spike in the incidence of several cancers as much as twothirds of the oral sabin and injected salk polio vaccine supply given from 1955 to 1963 in the. Recombinant viral vector biosafety levels stanford. Dec 15, 2004 the inadvertent and unrecognized presence of simian virus 40 sv40 in the commercial inactivated salk poliovaccines administered between 1955 and 1963 resulted in the potential exposure of millions of individuals, in the united states and elsewhere, to this polyomavirus of the rhesus macaque.
Simian virus 40 sv40 was first isolated in 1960 from cultures of rhesus monkey kidney cells used to produce poliovirus vaccines and was assigned to the family of polyomaviridae, polyomavirus genus, closely related to human polyomaviruses bk, jc, ki and wu, based on genomic organization and sequence similarity. Adenoassociated virus aav as a vector for gene therapy michael f. Simian virus 40 sv40 belongs to polyoma viruses group. Introduction simian virus 40 sv40 was an inadvertent contaminant of the early poliovirus vaccines used throughout much of the world during the late 1950s and early 1960s. Simian virus 40 sv40, a possible human polyomavirus. The polyomavirus simian virus 40 sv40 is a potent dna tumor virus, and mounting evidence suggests that it is an emergent human pathogen 1, 10, 12, 39, 49, 50, 66, 111, 123. Review of sv40 contamination of polio vaccine pdf,569kb. Consequently, we devised a gene transfer system based on simian virus 40 sv40 1 as a vector. This recombinant dna technology lecture is to explain about the properties of mammalian expression vector and the details of the construction of. The inadvertent and unrecognized presence of simian virus 40 sv40 in the commercial inactivated salk poliovaccines administered between 1955 and 1963 resulted in the potential exposure of millions of individuals, in the united states and elsewhere, to this polyomavirus of the rhesus macaque.
Oct 29, 2007 this work examines the feasibility of applying simian virus 40 sv40 vectors for pulmonary gene therapy. They enter cells and hijack their synthetic machinery, forcing them to create new viruses. This page is informational only this vector is not available from addgene please contact the manufacturer for further details. Like other polyomaviruses, sv40 is a dna virus that has the potential to cause tumors. Paul berg used a modified sv40 virus containing dna from the bacteriophage. Simian virus 40 is an example of how simple a virus can be and still perform its deadly job. Fortunately, functions provided by helper dna molecules might help to overcome these problems. Jonas salk and the oral or live polio vaccine opv created by dr. Consequently, we devised a gene transfer system based on simian virus40 sv40 1 as a vector. Since these small genomes do not have much dispensable dna, it is almost impossible to construct a functional vector with any added genes to it.
Recent molecular biology and epidemiological studies suggest that sv40 may be contagiously transmitted in humans by horizontal infection, independently from the earlier administration of sv40 contaminated vaccines. Its genome has ds circular dna wrapped up as nucleosome with the help of. In the baculovirus prototype autographa californica multiple nucleopolyhedrovirus acmnpv, the polyhedrin promoter very late promoter transcribes its gene by a viral rna polymerase therefore there is no supporting. Sv40 t antigencontaining cells should not be considered more hazardous than the intact virus. Sv40 has been widely studied as a model eukaryotic virus, leading to many early discoveries in eukaryotic dna.
The vector also contains an ampicillin resistance gene amp. Sv40 infects a wide range of cell types from humans and other mammals, and expresses its genes in them. In vitro assembly of sv40 virions and pseudovirions. Since the mass immunization program for polio began in 1955, before the. Adenoassociated virus shuttle plasmids viral vector. Vector information piresneo3 vector information pt36455 catalog no. Sepsis remains the leading cause of death in critically ill patients. The resulting plasmids, named prsvluc and prsvgfp, respectively, were. Nov 26, 2015 this recombinant dna technology lecture is to explain about the properties of mammalian expression vector and the details of the construction of mammalian expression vector.
Simian virus40 as a gene therapy vector dna and cell. It was found in the inactivated salk polio vaccine and some experimental lots. Its genome has ds circular dna wrapped up as nucleosome with the help of histone proteins. Nucleotide sequence of a conserved sv40 dna segment containing the origin of viral dna replication as an inverted repetition.
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