Did you mean: simian virus
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Frontiers in Immunology 2018Viruses efficiently transfer and express their genes in host cells and evolve to evade the host's defense responses. These properties render them highly attractive for... (Review)
Review
Viruses efficiently transfer and express their genes in host cells and evolve to evade the host's defense responses. These properties render them highly attractive for use as gene delivery vectors in vaccines, gene, and immunotherapies. Among the viruses used as gene delivery vectors, the macaque polyomavirus Simian Virus 40 (SV40) is unique in its capacity to evade intracellular antiviral defense responses upon cell entry. We here describe the unique way by which SV40 particles deliver their genomes in the nucleus of permissive cells and how they prevent presentation of viral antigens to the host's immune system. The non-immunogenicity in its natural host is not only of benefit to the virus but also to us in developing effective SV40 vector-based treatments for today's major human diseases.
Topics: Cytoplasm; Gene Transfer Techniques; Genetic Therapy; Genetic Vectors; Humans; Protein Transport; Simian virus 40
PubMed: 29892296
DOI: 10.3389/fimmu.2018.01160 -
Soft Matter Mar 2020Viruses are remarkable self-assembled nanobiomaterial-based machines, exposed to a wide range of pH values. Extreme pH values can induce dramatic structural changes,...
Viruses are remarkable self-assembled nanobiomaterial-based machines, exposed to a wide range of pH values. Extreme pH values can induce dramatic structural changes, critical for the function of the virus nanoparticles, including assembly and genome uncoating. Tuning cargo-capsid interactions is essential for designing virus-based delivery systems. Here we show how pH controls the structure and activity of wild-type simian virus 40 (wtSV40) and the interplay between its cargo and capsid. Using cryo-TEM and solution X-ray scattering, we found that wtSV40 was stable between pH 5.5 and 9, and only slightly swelled with increasing pH. At pH 3, the particles aggregated, while capsid protein pentamers continued to coat the virus cargo but lost their positional correlations. Infectivity was only partly lost after the particles were returned to pH 7. At pH 10 or higher, the particles were unstable, lost their infectivity, and disassembled. Using time-resolved experiments we discovered that disassembly began by swelling of the particles, poking a hole in the capsid through which the genetic cargo escaped, followed by a slight shrinking of the capsids and complete disassembly. These findings provide insight into the fundamental intermolecular forces, essential for SV40 function, and for designing virus-based nanobiomaterials, including delivery systems and antiviral drugs.
Topics: Capsid Proteins; Genome, Viral; Humans; Hydrogen-Ion Concentration; Models, Molecular; Nanoparticles; Simian virus 40
PubMed: 32104873
DOI: 10.1039/c9sm02436k -
Clinical Microbiology Reviews Jul 2004The polyomavirus simian virus 40 (SV40) is a known oncogenic DNA virus which induces primary brain and bone cancers, malignant mesothelioma, and lymphomas in laboratory... (Review)
Review
The polyomavirus simian virus 40 (SV40) is a known oncogenic DNA virus which induces primary brain and bone cancers, malignant mesothelioma, and lymphomas in laboratory animals. Persuasive evidence now indicates that SV40 is causing infections in humans today and represents an emerging pathogen. A meta-analysis of molecular, pathological, and clinical data from 1,793 cancer patients indicates that there is a significant excess risk of SV40 associated with human primary brain cancers, primary bone cancers, malignant mesothelioma, and non-Hodgkin's lymphoma. Experimental data strongly suggest that SV40 may be functionally important in the development of some of those human malignancies. Therefore, the major types of tumors induced by SV40 in laboratory animals are the same as those human malignancies found to contain SV40 markers. The Institute of Medicine recently concluded that "the biological evidence is of moderate strength that SV40 exposure could lead to cancer in humans under natural conditions." This review analyzes the accumulating data that indicate that SV40 is a pathogen which has a possible etiologic role in human malignancies. Future research directions are considered.
Topics: Humans; Neoplasms; Polyomavirus Infections; Simian virus 40; Tumor Virus Infections
PubMed: 15258090
DOI: 10.1128/CMR.17.3.495-508.2004 -
Microbiology and Molecular Biology... Jun 2002Simian virus 40 (SV40) is a small DNA tumor virus that has been extensively characterized due to its relatively simple genetic organization and the ease with which its... (Review)
Review
Simian virus 40 (SV40) is a small DNA tumor virus that has been extensively characterized due to its relatively simple genetic organization and the ease with which its genome is manipulated. The large and small tumor antigens (T antigens) are the major regulatory proteins encoded by SV40. Large T antigen is responsible for both viral and cellular transcriptional regulation, virion assembly, viral DNA replication, and alteration of the cell cycle. Deciphering how a single protein can perform such numerous and diverse functions has remained elusive. Recently it was established that the SV40 T antigens, including large T antigen, are molecular chaperones, each with a functioning DnaJ domain. The molecular chaperones were originally identified as bacterial genes essential for bacteriophage growth and have since been shown to be conserved in eukaryotes, participating in an array of both viral and cellular processes. This review discusses the mechanisms of DnaJ/Hsc70 interactions and how they are used by T antigen to control viral replication and tumorigenesis. The use of the DnaJ/Hsc70 system by SV40 and other viruses suggests an important role for these molecular chaperones in the regulation of the mammalian cell cycle and sheds light on the enigmatic SV40 T antigen-a most amazing molecule.
Topics: Amino Acid Sequence; Animals; Antigens, Polyomavirus Transforming; Cell Transformation, Neoplastic; Models, Biological; Models, Molecular; Molecular Chaperones; Molecular Sequence Data; Polyomavirus Infections; Retinoblastoma Protein; Simian virus 40; Tumor Suppressor Protein p53; Tumor Virus Infections; Virus Replication
PubMed: 12040123
DOI: 10.1128/MMBR.66.2.179-202.2002 -
Journal of Virology Jun 2018During entry, polyomavirus (PyV) is endocytosed and sorts to the endoplasmic reticulum (ER), where it penetrates the ER membrane to reach the cytosol. From the cytosol,...
During entry, polyomavirus (PyV) is endocytosed and sorts to the endoplasmic reticulum (ER), where it penetrates the ER membrane to reach the cytosol. From the cytosol, the virus moves to the nucleus to cause infection. How PyV is transported from the cytosol into the nucleus, a crucial infection step, is unclear. We found that upon reaching the cytosol, the archetypal PyV simian virus 40 (SV40) recruits the cytoplasmic dynein motor, which disassembles the viral particle. This reaction enables the resulting disassembled virus to enter the nucleus to promote infection. Our findings reveal how a cytosolic motor can be hijacked to impart conformational changes to a viral particle, a process essential for successful infection. How a nonenveloped virus successfully traffics from the cell surface to the nucleus to cause infection remains enigmatic in many instances. In the case of the nonenveloped PyV, the viral particle is sorted from the plasma membrane to the ER and then the cytosol, from which it enters the nucleus to promote infection. The molecular mechanism by which PyV reaches the nucleus from the cytosol is not entirely clear. Here we demonstrate that the prototype PyV SV40 recruits dynein upon reaching the cytosol. Importantly, this cellular motor disassembles the viral particle during cytosol-to-nucleus transport to cause infection.
Topics: Animals; COS Cells; Cell Line; Cell Nucleus; Chlorocebus aethiops; Cytosol; Dyneins; Fibroblasts; Protein Interaction Mapping; Simian virus 40; Virus Internalization
PubMed: 29593037
DOI: 10.1128/JVI.00353-18 -
Bulletin of the World Health... 2000From 1955 through early 1963, millions of people were inadvertently exposed to simian virus 40 (SV40) as a contaminant of poliovirus vaccines; the virus had been present... (Review)
Review
From 1955 through early 1963, millions of people were inadvertently exposed to simian virus 40 (SV40) as a contaminant of poliovirus vaccines; the virus had been present in the monkey kidney cultures used to prepare the vaccines and had escaped detection. SV40 was discovered in 1960 and subsequently eliminated from poliovirus vaccines. This article reviews current knowledge about SV40 and considers public responses to reports in the media. SV40 is a potent tumour virus with broad tissue tropism that induces tumours in rodents and transforms cultured cells from many species. It is also an important laboratory model for basic studies of molecular processes in eukaryotic cells and mechanisms of neoplastic transformation. SV40 neutralizing antibodies have been detected in individuals not exposed to contaminated poliovirus vaccines. There have been many reports of detection of SV40 DNA in human tumours, especially mesotheliomas, brain tumours and osteosarcomas; and DNA sequence analyses have ruled out the possibility that the viral DNA in tumours was due to laboratory contamination or that the virus had been misidentified. However, additional studies are necessary to prove that SV40 is the cause of certain human cancers. A recently published review article evaluated the status of the field and received much media attention. The public response emphasized that there is great interest in the possibility of health risks today from vaccinations received in the past.
Topics: Animals; Drug Contamination; Humans; Mass Media; Neoplasms; Poliovirus Vaccine, Inactivated; Simian virus 40; Tumor Virus Infections
PubMed: 10743284
DOI: No ID Found -
Current Protocols in Microbiology Aug 2017Simian virus 40 (SV40) is one of the best-characterized members of the polyomavirus family of small DNA tumor viruses. It has a small genome of 5243 bp and utilizes...
Simian virus 40 (SV40) is one of the best-characterized members of the polyomavirus family of small DNA tumor viruses. It has a small genome of 5243 bp and utilizes cellular proteins for its molecular biology, with the exception of the T-antigen protein, which is coded by the virus and is involved in regulating transcription and directing replication. Importantly, SV40 exists as chromatin in both the virus particle and intracellular minichromosomes. These facts, combined with high yields of virus and minichromosomes following infection and ease of manipulation, have made SV40 an extremely useful model to study all aspects of eukaryotic molecular biology. This unit describes procedures for working with SV40 and preparing SV40 chromatin from infected cells and virus particles, as well as procedures for using SV40 chromatin to study epigenetic regulation. © 2017 by John Wiley & Sons, Inc.
Topics: Animals; Epigenesis, Genetic; Epigenomics; Humans; Polyomavirus Infections; Simian virus 40; Tumor Virus Infections; Virus Cultivation
PubMed: 28800155
DOI: 10.1002/cpmc.35 -
Journal of Structural Biology Dec 2017Virus structures were among the earliest illustrations of how regulated protein assembly can proceed by folding of polypeptide-chain segments into complementary sites on...
Virus structures were among the earliest illustrations of how regulated protein assembly can proceed by folding of polypeptide-chain segments into complementary sites on partner proteins. I draw on Caspar's image of protein "tentacles" and his metaphor of SV40 pentamers as five-legged, aquatic organisms ("pentopuses") to suggest a helpful vocabulary. "Tentacular interactions" among component subunits organize most subcellular molecular machines. Their selective advantages include facile regulation of both assembly and disassembly by modifying enzymes and by folding chaperones.
Topics: Molecular Chaperones; Protein Folding; Simian virus 40; Viral Proteins; Viruses
PubMed: 28559165
DOI: 10.1016/j.jsb.2017.05.012 -
Journal of Virology Mar 1976Intact wild-type simian virus 40 particles can be separated and resolved from a temperature-sensitive mutant and from a number of other viruses by agarose gel... (Comparative Study)
Comparative Study
Intact wild-type simian virus 40 particles can be separated and resolved from a temperature-sensitive mutant and from a number of other viruses by agarose gel electrophoresis. The relative mobilities of the viruses appear to be a function of both virion size and surface composition. The virions of a temperature-sensitive strain of simian virus 40, tsB204, have significantly greater mobility than those of wild-type simian virus 40, when electrophoresis was conducted toward the cathode at pH 5.0. When electrophoresis was performed toward the anode at pH 7.0, TSB204 viruses have a slightly slower mobility as compared with that of the wild type. The data indicated that the virions of tsB204 have a greater positive charge at their surface than those of wild-type particles. No differences were detected in the finger print patterns of the tryptic peptides of VP1 and VP3 of these two virus strains. Although it was not possible to identify the structural polypeptide directly affected by the tsB204 mutation, we have shown that this mutation affects charge distribution on the surface of the virion.
Topics: Electrophoresis, Agar Gel; Mutation; Peptides; Simian virus 40; Temperature; Viral Proteins
PubMed: 176451
DOI: 10.1128/JVI.17.3.916-923.1976 -
Journal of Virology Oct 1978Polyacrylamide gel electrophoresis and tryptic peptide fingerprint analysis of the proteins made in a cell-free system derived from L-cells and immunoprecipitated with...
Polyacrylamide gel electrophoresis and tryptic peptide fingerprint analysis of the proteins made in a cell-free system derived from L-cells and immunoprecipitated with simian virus 40 (SV40) anti-T serum demonstrated that both SV40 large-T and small-T antigens are synthesized in vitro in response to mRNA isolated from productively infected CV1 CELLS. Sucrose density centrifugation in gradients containing 85% formamide showed that the mRNA's for both forms of T-antigen sediment at about 17.5S, with the mRNA for small-t sedimenting marginally, but reproducibly, ahead of the mRNA for large-T. Hybridization experiments using restriction endonuclease fragments Hae III-E and Hind II/III-B showed that all fractions active in the cell-free synthesis of both forms of T-antigen hybridized equally to both fragments. This suggests that the mRNA's for SV40 T-antigens are at least partly virus coded and that the bulk of the early SV40 mRNA contains sequence information from both ends of the early region. The data are consistent with the suggestion that the large-T mRNA is spliced. SV40 complementary RNA (the product of transcription of SV40 DNA using Escherichia coli RNA polymerase) was also translated in the L-cell system and gave two families of polypeptides which specifically immunoprecipitate with anti-T serum. One family (the small-t family) includes a polypeptide indistinguishable by gel electrophoresis and tryptic peptide fingerprinting from small-t isolated from cells. The other family (the 60K family) has a major component with molecular weight approximately 60,000 and includes other polypeptides with molecular weights ranging from approximately 14,000 to about 70,000. The 60K family has petides in common with large-T but not with small-T. Together, the peptides of the small-t and 60K families account for virtually all of the methionine peptides of SV40 large-T. We conclude from these results (i) that small-t is probably entirely, and large-T at least predominantly, virus coded; (ii) that the small-t and 60K families represent the translation products of two different portions of the early region of SV40 DNA (approximately 0.65 to 0.55 map units and 0.54 to 0.17 map units); and (iii) that although most, if not all, of the large-T and small-t peptides are present in the cell-free product, some feature of sequence arrangement of SV40 complementary RNA prevents the translation of full-length large-T and results instead in the synthesis of fragments. We suggest that the absence of a splice in the complementary RNA is responsible for this result.
Topics: Antigens, Viral; Base Sequence; Cell-Free System; L Cells; Molecular Weight; Peptide Biosynthesis; Protein Biosynthesis; RNA, Messenger; RNA, Viral; Simian virus 40; Viral Proteins
PubMed: 212600
DOI: 10.1128/JVI.28.1.154-170.1978