Tissue culture adaptation of natural isolates of simian virus 40: changes occur in viral regulatory region but not in carboxy-terminal domain of large T-antigen.

Lednicky, John A.; Butel, Janet S.

doi:10.1099/0022-1317-78-7-1697

Cited by 38 publications

(37 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These changes occur relative to the structure of a viral species-specific basic regulatory region termed archetypal or protoarchetypal (3,25,35). In contrast, the Tag-C region of SV40 strains can vary in sequence and in length but does not appear to change in response to growth in vitro or in vivo (18,23,24,31). We and others have previously proposed the identification of SV40 strains based on T-ag-C sequences (18,23,24,31,40).…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, the Tag-C region of SV40 strains can vary in sequence and in length but does not appear to change in response to growth in vitro or in vivo (18,23,24,31). We and others have previously proposed the identification of SV40 strains based on T-ag-C sequences (18,23,24,31,40). The analyses described here confirmed the validity of the use of the T-ag-C domain for genotyping SV40 isolates and tissue-associated sequences.…”

Section: Discussionmentioning

confidence: 99%

“…Alignment gaps were treated as missing data in the whole-genome analysis; therefore, part of the regulatory region (nucleotides 29 to 246 [according to SV40-776 numbering]) was excluded from the analysis. These nucleotides (29 to 246) encompass part of the early promoter and part of the enhancer (24,25); the core ori was essentially intact (24,25). Under these conditions, there were few alignment gaps and no ambiguous positions in the alignment.…”

Section: Sv40 Sequences Analyzedmentioning

confidence: 99%

“…The T-ag-C sequence was shown to be stable during tissue culture passage of SV40 isolates (24). In contrast, the SV40 regulatory region may contain large insertions, deletions, or duplications (25), and rearrangements have been observed to occur within individual infected monkeys (23,31) and during passage of SV40 in certain cultured cells (32).…”

mentioning

confidence: 99%

See 3 more Smart Citations

Phylogenetic Analysis of Polyomavirus Simian Virus 40 from Monkeys and Humans Reveals Genetic Variation

Forsman

Lednicky

Fox

et al. 2004

J Virol

View full text Add to dashboard Cite

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, Rh911, and K661), and from human tumors (strains SVCPC and SVMEN). Thus, adaptation is not essential for SV40 survival in humans. The C terminus of the T-antigen (T-ag-C) gene contains the highest proportion of variable sites in the SV40 genome. An analysis based on just the T-ag-C region was highly congruent with the whole-genome analysis; hence, sequencing of just this one region is useful in strain identification. Analysis of an additional 16 strains for which only the T-ag-C gene was sequenced indicated that further SV40 genetic diversity is likely, resulting in a provisional clade (clade C) that currently contains strains associated with human tumors and human strain PML-1. Four other polymorphic regions in the genome were also identified. If these regions were analyzed in conjunction with the T-ag-C region, most of the phylogenetic signal could be captured without complete genome sequencing. This report represents the first whole-genome approach to establishing phylogenetic relatedness among different strains of SV40. It will be important in the future to develop a more complete catalog of SV40 variation in its natural monkey host, to determine if SV40 strains from different clades vary in biological or pathogenic properties, and to identify which SV40 strains are transmissible among humans.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Sv40 Sequences Analyzedmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Phylogenetic Analysis of Polyomavirus Simian Virus 40 from Monkeys and Humans Reveals Genetic Variation

Forsman

Lednicky

Fox

et al. 2004

J Virol

View full text Add to dashboard Cite

show abstract

“…We discovered an influence of the viral regulatory region on SV40 pathogenesis in vivo that is not evident in transformation assays in vitro. parental viruses have been described previously (23,24,29,44,45). T-ag-C recombinant viruses were constructed using backbones from parental strains 776(2E) and SVCPC.…”

mentioning

confidence: 99%

Influence of the Viral Regulatory Region on Tumor Induction by Simian Virus 40 in Hamsters

Šroller

Vilchez

Stewart

et al. 2008

J Virol

View full text Add to dashboard Cite

Most of the simian virus 40 (SV40) genome is conserved among isolates, but the noncoding regulatory region and the genomic region encoding the large T-antigen C terminus (T-ag-C) may exhibit considerable variation. We demonstrate here that SV40 isolates differ in their oncogenic potentials in Syrian golden hamsters. Experimental animals were inoculated intraperitoneally with 10 7 PFU of parental or recombinant SV40 viruses and were observed for 12 months to identify genetic determinants of oncogenicity. The viral regulatory region was found to exert a statistically significant influence on tumor incidence, whereas the T-ag-C played a minor role. Viruses with a single enhancer (1E) were more oncogenic than those with a two-enhancer (2E) structure. Rearrangements in the 1E viral regulatory region were detected in 4 of 60 (6.7%) tumors. Viral loads in tumors varied, with a median of 5.4 SV40 genome copies per cell. Infectious SV40 was rescued from 15 of 37 (40%) cell lines established from tumors. Most hamsters with tumors and many without tumors produced antibodies to T antigen. All viruses displayed similar transforming frequencies in vitro, suggesting that differences in oncogenic potential in vivo were due to host responses to viral infection. This study shows that SV40 strains differ in their biological properties, suggests that SV40 replicates to some level in hamsters, and indicates that the outcome of an SV40 infection may depend on the viral strain present.Simian virus 40 (SV40) is a member of the family Polyomaviridae and is known for its ability to induce malignancies in the Syrian golden hamster (Mesocricetus auratus) model (9-11, 16, 20, 32). SV40 was discovered as an inadvertent contaminant of early forms of poliovirus and adenovirus vaccines (9, 46) that were prepared in primary cultures of kidney cells from rhesus monkeys, which are often naturally infected with the virus (9, 43, 51). Since its discovery, SV40 has been an important model for studies of virus-induced cancers and of viral effects on eukaryotic cell processes (1, 5). SV40 has been found to cause human infections and to be associated with some human malignancies (9, 21, 52).Phylogenetic analysis has recently established that strains of SV40 exist and can be grouped into clades or genogroups (18). Strains are identified by nucleotide differences at the C terminus of the large tumor antigen (T-ag) gene (T-ag-C) that result in amino acid changes in the protein. The SV40 large T-ag protein is essential for viral replication and is the major viral oncoprotein (1, 9, 32). Strains of SV40 can diverge in the structures of their noncoding regulatory regions (9,23,26,45), generating what are termed variants. SV40 variants containing a partial or complete duplication of the 72-bp enhancer element or other sequence rearrangements are designated as having complex regulatory regions, and those with one enhancer are designated as having a simple or archetypal regulatory region structure (23,26). It has been demonstrated that increased numbers of enha...

show abstract

Serological evidence of SV40 infections in HIV-infected and HIV-negative adults

et al. 1998

View full text Add to dashboard Cite

SV40 is a simian polyomavirus that was a contaminant of some viral vaccines administered to people between 1955 and 1962. SV40 DNA has recently been found associated with several types of human tumors, suggesting that the virus is present in humans. We examined sera from patients infected with human immunodeficiency virus type 1 (HIV-1) as well as from HIV-1-negative controls to determine the prevalence of SV40 neutralizing antibodies using a specific plaque reduction assay. We found that 16.1% of HIV-infected patients (n = 236) were seropositive for SV40, as compared to 12.0% of HIV-negative control volunteers (n = 108) and 11.1% of HIV-negative patients (n = 72). These differences were not statistically significant. As individuals born between 1941 and 1962 had the highest chance of having received SV40-contaminated poliovaccines, we analyzed SV40 seropositivity rates based on year of birth. SV40 antibody rates for HIV-infected patients born before 1941, between 1941 and 1962, and after 1962 were 17.1%, 16.3%, and 11.8%, respectively. For the HIV-negative subjects, the rates were 12.5%, 12.0%, and 9.7%, respectively. There was no correlation between SV40 seropositivity and either the stage of disease in HIV-infected patients or the race/ethnicity. Also, there was no correlation between the presence of SV40 neutralizing antibody and the titer of neutralizing antibody to human polyomavirus BKV. The SV40 seropositivity rates in the patients born between 1941 and 1962 may be explained by the likelihood of those individuals having received SV40-contaminated vaccines, but the detection of SV40 neutralizing antibody in individuals born after 1962 (with no risk of having received contaminated vaccines) is significant. Although cross-reactive antibodies might theoretically contribute to the observed reactivities, these results suggest that SV40 neutralizing antibodies are present in certain individuals and raise the possibility that SV40 continues to infect humans long after vaccines were freed from contamination.

show abstract

Tissue culture adaptation of natural isolates of simian virus 40: changes occur in viral regulatory region but not in carboxy-terminal domain of large T-antigen.

Cited by 38 publications

References 47 publications

Phylogenetic Analysis of Polyomavirus Simian Virus 40 from Monkeys and Humans Reveals Genetic Variation

Phylogenetic Analysis of Polyomavirus Simian Virus 40 from Monkeys and Humans Reveals Genetic Variation

Influence of the Viral Regulatory Region on Tumor Induction by Simian Virus 40 in Hamsters

Serological evidence of SV40 infections in HIV-infected and HIV-negative adults

Contact Info

Product

Resources

About