Molecular Analysis of SV-40-CAL, a New Slow Growing SV-40 Strain from the Kidney of a Caged New World Monkey with Fatal Renal Disease (original) (raw)
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Genetic analysis of simian virus 40 from brains and kidneys of macaque monkeys
Journal of Virology, 1992
Simian virus 40 (SV40) was isolated from the brains of three rhesus monkeys and the kidneys of two other rhesus monkeys with simian immunodeficiency virus-induced immunodeficiency. A striking feature of these five cases was the tissue specificity of the SV40 replication. SV40 was also isolated from the kidney of a Taiwanese rock macaque with immunodeficiency probably caused by type D retrovirus infection. Multiple full-length clones were derived from all six fresh SV40 isolates, and two separate regions of their genomes were sequenced: the origin (ori)-enhancer region and the coding region for the carboxy terminus of T antigen (T-ag). None of the 23 clones analyzed had two 72-bp enhancer elements as are present in the commonly used laboratory strain 776 of SV40; 22 of these 23 clones were identical in their ori-enhancer sequences, and these had only a single 72-bp enhancer element. We found no evidence for differences in ori-enhancer sequences associated with tissue-specific SV40 re...
Cell and Molecular Biology of Simian Virus 40: Implications for Human Infections and Disease
JNCI Journal of the National Cancer Institute, 1999
Simian virus 40 (SV40), a polyomavirus of rhesus macaque origin, was discovered in 1960 as a contaminant of polio vaccines that were distributed to millions of people from 1955 through early 1963. SV40 is a potent DNA tumor virus that induces tumors in rodents and transforms many types of cells in culture, including those of human origin. This virus has been a favored laboratory model for mechanistic studies of molecular processes in eukaryotic cells and of cellular transformation. The viral replication protein, named large T antigen (T-ag), is also the viral oncoprotein. There is a single serotype of SV40, but multiple strains of virus exist that are distinguishable by nucleotide differences in the regulatory region of the viral genome and in the part of the Tag gene that encodes the protein's carboxyl terminus. Natural infections in monkeys by SV40 are usually benign but may become pathogenic in immunocompromised animals, and multiple tissues can be infected. SV40 can replicate in certain types of simian and human cells. SV40-neutralizing antibodies have been detected in individuals not exposed to contaminated polio vaccines. SV40 DNA has been identified in some normal human tissues, and there are accumulating reports of detection of SV40 DNA and/or Tag in a variety of human tumors. This review presents aspects of replication and cell transformation by SV40 and considers their implications for human infections and disease pathogenesis by the virus. Critical assessment of virologic and epidemiologic data suggests a probable causative role for SV40 in certain human cancers, but additional studies are necessary to prove etiology. [J Natl Cancer Inst 1999;91: 119-34] SHIFTING PARADIGMS Evidence is mounting that simian virus 40 (SV40) infects humans and is associated with certain types of human tumors. These observations were unexpected, because SV40 generally has been considered to be a monkey virus that rarely infected humans and played no role in human disease. In this era of revolutionary advances in biology, wellaccepted biologic concepts have undergone change. Recent findings suggest that the concepts of the rarity of SV40 infection in humans and the innocuousness of those infections are also in need of re-evaluation. This review will present selected aspects of the cell and molecular biology of SV40 and will evaluate those properties for their possible implications for human infection and disease pathogenesis. More comprehensive reviews of SV40 have recently been published (1-3).
Journal of the American Society of Nephrology, 2002
Simian virus 40 (SV40), a monkey polyomavirus that is believed to have entered the human population through contaminated vaccines, is known to be renotropic in simians. If indeed SV40 is endemic within the human population, the route of transmission is unknown. It was therefore hypothesized that SV40 might be renotropic in humans and be detected more frequently in samples obtained from patients with kidney diseases. This study found that typical polyomavirus cytopathic effects (CPE) were present and SV40 T antigen was detected in CV-1 cells cultured with peripheral blood mononuclear cells (PBMC) or urinary cells obtained from patients with kidney disease and healthy volunteers. DNA sequences homologous to the SV40 viral regulatory genome were detected by PCR in urinary cells from 15 (41%) of 36 patients with focal segmental glomerulosclerosis (FSGS), 2 (10%) of 20 patients with other kidney diseases, and 1 (4%) of 22
The incidence of simian virus 40 (SV40) infections in rhesus macaques infected with simian-human immu-nodeficiency viruses (SHIV) and in uninfected animals was determined using PCR. Rates varied from 5% in peripheral blood mononuclear cells of uninfected monkeys to 19.6% in SHIV-infected macaques. Much higher detection rates, up to 75%, were found in lymph nodes and spleen samples of SHIV-infected animals. Sequence analysis of PCR amplicons revealed that they form two genetic clusters, one containing the majority of known SV40 strains and the other formed by variants with 7% genetic difference. Based on this difference, we propose two SV40 types: " type 1 " or " classical type " for the majority of SV40 strains and " type 2 " for the novel SV40 variants. The genome of one variant, SV40-Ri257, was completely sequenced and analyzed. The agnogene of SV40-Ri257 extends into the VP2 open reading frame and encodes a typical agnoprotein fused to a C-terminal hydrophobic region. The transcriptional control region (TCR) of SV40-Ri257 is the least conserved region compared to type 1 viruses. Particularly, the 3 end of the TCR, containing the early promoter and enhancer region, exhibits considerable variation. Further analysis of SHIV-infected macaques with type-specific PCRs revealed that the TCR of type 1 was completely conserved, whereas this region in type 2 varied considerably within the early enhancer region. We provide evidence here for the existence of a novel SV40 type in rhesus macaques and show that double infections with both types frequently occur.
Infectious Agents and Cancer, 2007
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. 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. SV40 footprints in humans have been found associated at high prevalence with specific tumor types such as brain and bone tumors, mesotheliomas and lymphomas and with kidney diseases, and at lower prevalence in blood samples from healthy donors. Contrasting reports appeared in the literature on the circulation of SV40 in humans by contagious transmission and its association, as a possible etiologic cofactor, with specific human tumors. As a consequence of the conflicting results, a considerable debate has developed in the scientific community. In the present review we consider the main results obtained by different groups investigating SV40 sequences in human tumors and in blood specimens, the putative role of SV40 in the onset/progression of specific human tumors, and comment on the hypotheses arising from these data.
Lack of Serologic Evidence for Prevalent Simian Virus 40 Infection in Humans
JNCI Journal of the National Cancer Institute, 2003
Background: Propagation of poliovirus in monkey kidney cells led to the inadvertent contamination of poliovirus vaccines with simian virus 40 (SV40) between 1955 and 1963. Recent studies using polymerase chain reaction-based strategies have detected SV40 DNA in a large number of tumor types. The finding of SV40 DNA in tumors from individuals who are too young to have been exposed to SV40-contaminated vaccines has led to the suggestion that SV40 has become a prevalent transmissible human pathogen. To test this hypothesis, we screened human sera for antibodies to SV40 using direct and competitive enzyme-linked immunosorbent assays (ELISAs). Methods: An ELISA was developed using recombinant SV40 virus-like particles (VLPs) and was validated using sera from naturally infected macaques. VLPs of SV40 and the related ubiquitous human polyomaviruses, JCV and BKV, were used to screen human sera to determine the prevalence of SV40, JCV, and BKV antibodies among a normal population of control subjects (n = 487) and among case patients with either osteosarcoma (n = 122) or prostate cancer (n = 90). A competitive ELISA in which sera were pre-adsorbed with each type of VLP was used to identify cross-reactive antibodies. Correlations of reactivity among the three polyomavirus types were calculated using the Spearman correlation coefficient. All statistical tests were two-sided. Results: BKV and JCV antibodies were prevalent in all case patients and control subjects examined. In contrast, only 6.6% (46/699) of serum samples were positive for SV40 antibodies by ELISA; however, none of these samples could be confirmed as having authentic SV40 antibodies following pre-adsorption with JCV or BKV VLPs. Conclusion: These data indicate that some individuals have BKV and/or JCV antibodies that cross-react with SV40, but they do not provide support for SV40 being a prevalent human patho-
Journal of Virology, 2004
A phylogenetic analysis of 14 complete simian virus 40 (SV40) genomes was conducted in order to determine strain relatedness and the extent of genetic variation. This analysis included infectious isolates recovered between 1960 and 1999 from primary cultures of monkey kidney cells, from contaminated poliovaccines and an adenovirus seed stock, from human malignancies, and from transformed human cells. Maximum-parsimony and distance methods revealed distinct SV40 clades. However, no clear patterns of association between genotype and viral source were apparent. One clade (clade A) is derived from strain 776, the reference strain of SV40. Clade B contains isolates from poliovaccines (strains 777 and Baylor), from monkeys (strains N128,
Journal of Molecular Biology, 1971
The number of SV40$ gcnome equivalents present in green monkey and SV40 transformed mammalian DNA's have been evaluated by measuring DNA reassociation kinetics on hydroxyapatite. Under the proper conditions, this method is s&iciently sensitive to detect less than one SV40 DNA molecule per mammalian genome (one part in 106) as shown by reconstruction experiments. In four out of five SV40 transformed lines examined, an average of one SV40 genome equivalent was present in the cell DNA; three SV40 DNA equivalents per cell were found in the fifth viral transformed line. The background level of SV40 DNA sequences within the 3T3 genome was 0.45 equivalent per cell. An average of 0.5 SV40 genome equivalent was measured per African green monkey genome, an amount too small to be reliably detected using DNA-DNA hybridization on nitrocellulose membranes. The biological significance of these results and their relationship to previously reported values are discussed.