Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Virus Integration”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources
PubMed1986

Hepatitis B virus integration site in hepatocellular carcinoma at chromosome 17;18 translocation.

Integrated hepatitis B virus (HBV) DNA is almost invariably found in hepatocellular carcinomas (HCC) which develop in HBV carriers. Integrated HBV DNAs from two single-integration HCCs (C3 and C4) have been cloned, and the cellular integration sites have been analyzed. Integrated HBV DNA of C3 is present in chromosome 6 and contains a nearly complete linear HBV genome. The HBV DNA integration in tumor C3 was not associated with major rearrangements of cellular DNA. In contrast, the integrated HBV DNA in C4 contains a large inverted repeat of HBV DNA, in which each repeat consists of a linear HBV DNA segment similar to that present in C3. The C4 integration was also accompanied by a cellular DNA translocation at the HBV integration site. The translocation occurred between chromosomes 17 and 18, along with a deletion of at least 1.3 kilobases of chromosome 18 DNA at the translocation site. Our data support a model in which postintegration rearrangement of integrated HBV and cellular DNA results in the generation of chromosomal aberrations. These chromosomal aberrations may function in a multistage mechanism leading to fully malignant HCC.

Base Sequence↗
PubMed2005

Simian immunodeficiency virus integration preference is similar to that of human immunodeficiency virus type 1.

Simian immunodeficiency virus (SIV) is a useful model for studying human immunodeficiency virus (HIV) pathogenesis and vaccine efficacy. As with all other retroviruses, integration is a necessary step in the replication cycle of SIV. The location of the retrovirus integration site is known to impact on viral gene expression, establishment of viral latency, and other aspects of the replication cycle of a retrovirus. In this study, 148 SIV provirus integration sites were sequenced and mapped in the human genome. Our analysis showed that SIV integration, like that of HIV type 1 (HIV-1), exhibited a strong preference for actively transcribed regions in the genome (A. R. Schroder et al., Cell 110:521-529, 2002) and no preference for the CpG islands or transcription start sites, in contrast to observations for murine leukemia virus (X. Wu et al., Science 300:1749-1751, 2003). The parallel integration target site preferences of SIV and HIV-1 suggest that these lentiviruses may share similar mechanisms for target site selection and that SIV serves as an accurate model of HIV-1 with respect to integration.

Cell Line↗
PubMed1984

Specific hepatitis B virus integration in hepatocellular carcinoma DNA through a viral 11-base-pair direct repeat.

Integrated hepatitis B virus (HBV) DNA sequences have been cloned from cellular DNA of two human liver tumors. The structure of the clones was determined by restriction mapping, and the host-viral DNA junctions were sequenced. In each clone one junction mapped to within an 11-base-pair sequence, 5' T-T-C-A-C-C-T-C-T-G-C, which is directly repeated near the extremities of the cohesive-end region of the free viral genome. The two copies of this sequence are termed DR1 and DR2. While one clone carried a host-viral junction within DR1, the second one carried a host-viral junction within DR2. The first 1 or 2 base pairs of the repeat were deleted upon recombination with the host genome, leaving at the junctions a common 9-base-pair segment of HBV DNA, 5' C-A-C-C-T-C-T-G-C. The other two host-viral junctions mapped to the pre-S region and to the core region of the viral genome, showing no peculiar feature. These results show that HBV DNA can integrate via a specific viral DNA sequence.

Base Composition↗
PubMed1989

Multicentric independent development of hepatocellular carcinoma revealed by analysis of hepatitis B virus integration pattern.

Two separate nodular lesions of hepatocellular carcinoma (HCC) were surgically removed from a patient with positive serum hepatitis B surface antigen. Southern blot analysis of DNA from the two separate HCC lesions showed different restriction patterns of integrated hepatitis B virus DNA, indicating their independent origins. The two lesions were composed mainly of poorly differentiated HCC; however, well-differentiated HCC was also observed in the periphery of the lesions. This histological finding is consistent with the multistep and independent development of HCC in each site of the liver.

Aged↗
PubMed1991

Chromosomal sites for hepatitis B virus integration in human hepatocellular carcinoma.

The discovery that hepatitis B virus (HBV) integrates into host chromosomes raises the question of whether such viral DNA integration correlates directly with the activation of specific oncogenes or the inactivation of anti-oncogenes. To obtain insight into this problem, we randomly collected HBV integrant samples from different human hepatocellular carcinomas and identified the site of chromosomal integration by using in situ hybridization and/or linkage analysis with the flanking cellular DNAs as probes. Our findings did not specifically identify particular HBV DNA integration sites in chromosomes, although chromosomes 11 and 17 seemed to have more than the average number of integrants.

Alleles↗
PubMed1985

Insertion of long interspersed repeated elements at the Igh (immunoglobulin heavy chain) and Mlvi-2 (Moloney leukemia virus integration 2) loci of rats.

Restriction enzyme analysis of normal DNA derived from individual rats of the National Institutes of Health outbred Osborn-Mendel colony revealed that two independent single-copy loci, the Igh (immunoglobulin heavy chain) locus and the Mlvi-2 (Moloney leukemia virus integration 2) locus, a putative oncogene, are polymorphic (i.e., exhibit allelic variation). The polymorphism at both loci was due to the presence or absence of a long interspersed repeated DNA element (LINE). The LINE insertion in the Igh locus occurred in the joining (J) region, which is involved in the physiological rearrangement of this locus. The LINE insertion in the Mlvi-2 locus has occurred approximately 6 kilobases from the region of provirus integration in Moloney murine leukemia virus-induced rat thymomas. The two inserts are colinear with each other and with other randomly selected cloned copies of the rat LINE family, the general characteristics of which we also present. LINE insertion in the Mlvi-2 locus was observed in several rat strains, established from independent rat colonies, suggesting that LINE-containing Mlvi-2 alleles may be widespread in the rat population. LINE insertion in the Igh locus was observed in 1 of 27 rats. The detection of a LINE-related polymorphism at two nonselected loci indicates that LINEs are transposable. The presence or absence of these long (greater than 5 kilobases), highly transcribed elements at single-copy loci could have profound effects on gene activity. Furthermore, LINE-containing single-copy loci could be affected by homologous interaction between the resident LINE and any of the other 50,000 or so copies of these elements in the rat genome.

Animals↗
PubMed1990

Human homologue of Moloney leukemia virus integration-4 locus (MLVI-4), located 20 kilobases 3' of the myc gene, is rearranged in multiple myelomas.

The structure of the c-myc locus and the flanking chromosomal region was investigated by Southern blot analysis of DNA from bone marrow aspirates from 42 patients with multiple myeloma. The main abnormality detected was the rearrangement of the MLVI-4 locus, 20 kilobases 3' of c-myc, which was observed in seven cases (16%). Two of these rearrangements were detected at the time of the initial diagnosis, four during treatment, and one at relapse, and their presence correlated with unresponsiveness to therapy. The MLVI-4 locus represents the human homologue of the Moloney leukemia virus integration-4 locus (Mlvi-4), a common region for provirus integration in Moloney murine leukemia virus-induced T-cell lymphomas in rodents. Provirus integration in this locus activates c-myc, and two additional genes, Mlvi-4 and Mlvi-1. The c-myc gene was rearranged in one patient; mutations involving the first exon of c-myc, frequently detected by altered restriction enzyme recognition sites in Burkitt's lymphomas, were not observed in these myelomas.

Chromosome Mapping↗
PubMed1998

Extensive analysis of duplicated-inverted hepatitis B virus integrations in human hepatocellular carcinoma.

Hepatitis B virus (HBV) DNA is found chromosomally integrated into the genome of the majority of hepatocellular carcinomas (HCC) arising in chronic HBV carriers suggesting that, in some instances, viral sequences may be directly responsible for oncogenic conversion. In an attempt to clarify the oncogenic potential of integrated HBV sequences, we performed an extensive analysis of two single integrations present in HCC which developed in non-cirrhotic livers from HBsAg-positive Korean patients. In both cases, integrated viral sequences were characterized by a duplicated-inverted configuration involving the flanking cellular sequences, a pattern consistently found in many amplicons isolated from mammalian cells. Integration sites are characterized by an AT-rich content and the presence of topoisomerase I and II cleavage target sequences as well as other recombination-prone motifs. The chromosomal locations of the integration sites were determined as 8q13 and 10q22 in the human genome, two regions known to harbour genes involved in tumorigenesis. The cis-activating potential of the integrations in their original configuration was also investigated in a transient transfection assay in HepG2 cells. Integrated sequences, rather than activating heterologous promoters, show either no activity or a weak tendency to inhibit activation of neighbouring reporter genes. The implications of our findings for the understanding of primary liver cancer development are discussed.

Adult↗
PubMed1995

Ecotropic virus integration site-1 gene preferentially expressed in post-myelodysplasia acute myeloid leukemia: possible association with GATA-1, GATA-2, and stem cell leukemia gene expression.

We investigated expression of the human ecotropic virus integration site-1 (EVI1) gene in patients with leukemia and myelodysplastic syndrome (MDS) using the reverse transcriptase-polymerase chain reaction (RT-PCR) method. The EVI1 transcripts were detected in 5 (10.0%) of 50 patients with de novo acute myeloid leukemia (AML), including two AML patients with trilineage myelodysplasia, and in 8 (34.8%) of 23 patients with post-myelodysplastic syndrome AML (post-MDS AML). EVI1 expression was also detected in 6 (35.3%) of 17 MDS patients and three of six patients with chronic myeloid leukemia (CML) in myelomegakaryoblast crisis. No EVI1 transcripts were detected in patients with acute lymphoid leukemia (n = 15) or CML in lymphoid blast crisis (n = 4). Chromosomal abnormalities at the 3q26 region, where the EVI1 gene is located, were found in one patient with MDS and two patients with CML myelomegakaryoblast crisis who had EVI1 expression. Our results showed that EVI1 expression was frequent in patients with post-MDS AML and AML with trilineage myelodysplasia, regardless of the presence or absence of 3q26 abnormalities. EVI1 expression was accompanied by expression of GATA-1 and GATA-2, and often by stem cell leukemia (SCL) gene expression. In patients with post-MDS AML, EVI1 expression was not always associated with a 3q26 abnormality, whereas EVI1 expression in CML myelomegakaryoblast crisis was often linked to a 3q26 abnormality. Our results suggest that the leukemogenic role of EVI1 expression may differ between post-MDS AML and leukemia, with EVI1 expression associated with a 3q26 abnormality.

Adult↗
PubMed2006

[Identification of hepatitis B virus integration sites in hepatocellular carcinoma tissues from patients with chronic hepatitis B].

OBJECTIVE: Hepatitis B virus (HBV) integration into the host genome is frequently detected in HBV positive hepatocellular carcinoma (HCC) in China. The aim of this study is to carry out a large-scale screening for the HBV integrations sites in HCC samples from Chinese patients. METHODS: Cellular DNA was extracted from 40 HBV-related HCC by proteinase K digestion/phenol extraction method. One primer specific to HBV sequence and another primer directed to human Alu repeat were used to amplify the virus/cellular DNA junction. To avoid undesirable amplifications between Alu sequences, primers were constructed with dUTPs and destroyed by uracil DNA glycosylase treatment after 15 initial cycles of amplification. Only desirable fragments were then further amplified with specific primers to the known region and to a tag sequence introduced in the Alu-Specific primer. The PCR product was purified and subject to direct sequencing by ABI 3700 Auto sequencer. NCBI (national center for biotechnology information) BLAST and MapViewer search were used for identification of HBV location on human genomes. RESULTS: In 40 HBsAg positive HCC samples, 34 (85%) were showed to have at least one copy of HBV fragment in host genome, indicating HBV-Alu-PCR is a rapid way for identification of new cellular DNA sequences adjacent to HBV. Analysis from the 68 isolated viral-cellular junctions, X gene was found to be interrupted at any length, not specifically at DR1 and DR2 regions. Three-prime-deleted X gene was observed in 65 (96%) cases. HBV preferred to integrate into the intron and the up-stream regulatory region of the cellular genes. In no case HBV inserted into the exon. Our results also demonstrated that the cellular genes targeted by HBV are usually key regulators of cell proliferation and cell death. Three genes, myeloid/lymphoid or mixed-lineage leukemia 4, G protein alpha transducing activity polypeptide 1 and fibronectin, were found to be recurrently targeted by HBV. CONCLUSION: HBV-Alu-PCR is a powerful tool for the study of HBV integration sites. Truncated X is a major form existed in the HBV integrants. HBV integration is not distributed evenly throughout the host genome and viral insertional mutagenesis may play an important role in the development of HCC.

Alu Elements↗
PubMed1986

A common mouse mammary tumor virus integration site in chemically induced precancerous mammary hyperplasias.

Mammary carcinomas can be induced by chemical and hormonal as well as viral carcinogens. Irrespective of the class of inducer, these tumors develop in discrete stages, of which alveolar hyperplasia is one of the earliest identifiable. Since carcinogenesis by the mammary tumor virus is now thought to involve proviral activation of adjacent cell genes at specific loci, we sought to determine if a similar mechanism also played a role in chemical and hormonal carcinogenesis and if its role was stage specific. Three high-tumor-incidence BALB/c hyperplastic alveolar nodule outgrowths of two different etiologies were found to have exogenous mouse mammary tumor virus proviruses integrated at the same site in the genome. This common site of integration is not within the bounds of the int-1 and int-2 loci into which proviruses detected at these loci are clustered in MMTV-induced mammary tumors. All three HANs are commonly impaired in end-point differentiation. We propose that mouse mammary tumor virus integration at this site is responsible for a specific abnormality in differentiation associated with the preneoplastic phenotype.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2004

Genome-wide analyses of avian sarcoma virus integration sites.

The chromosomal features that influence retroviral integration site selection are not well understood. Here, we report the mapping of 226 avian sarcoma virus (ASV) integration sites in the human genome. The results show that the sites are distributed over all chromosomes, and no global bias for integration site selection was detected. However, RNA polymerase II transcription units (protein-encoding genes) appear to be favored targets of ASV integration. The integration frequency within genes is similar to that previously described for murine leukemia virus but distinct from the higher frequency observed with human immunodeficiency virus type 1. We found no evidence for preferred ASV integration sites over the length of genes and immediate flanking regions. Microarray analysis of uninfected HeLa cells revealed that the expression levels of ASV target genes were similar to the median level for all genes represented in the array. Although expressed genes were targets for integration, we found no preference for integration into highly expressed genes. Our results provide a more detailed description of the chromosomal features that may influence ASV integration and support the idea that distinct, virus-specific mechanisms mediate integration site selection. Such differences may be relevant to viral pathogenesis and provide utility in retroviral vector design.

Avian Sarcoma Viruses↗
PubMedDate not supplied

Multiple rearrangements and activated expression of c-myc induced by woodchuck hepatitis virus integration in a primary liver tumour.

Woodchuck hepatitis virus (WHV) is a small, partially double-stranded DNA virus. Like the related human hepatitis B virus (HBV), WHV induces acute and chronic hepatitis and hepatocellular carcinoma (HCC) in its natural host. WHV DNA integration into c-myc and N-myc, resulting in deregulated expression of these genes, has been described previously in woodchuck HCC. We have analysed a woodchuck liver tumour in which WHV DNA was integrated in the c-myc gene. The virus insertion provoked multiple alterations in one c-myc allele, probably involving secondary deletions and mutations. Integrated viral DNA, including promotor and enhancer sequences, acted as an insertional mutagen, leading to enhanced expression of heterogenous c-myc transcripts ranging from 7.2 to 14 kb in size, strikingly longer than normal 2.3-kb c-myc RNA. These results provide an additional example in which the oncogenic activation of a myc gene by cis-acting effect of WHV insertion may play a critical role in virus-induced woodchuck HCC.

Animals↗
PubMedDate not supplied

Alteration of c-myc chromatin structure by avian leukosis virus integration.

The most common sites of integration of the leukosis virus (ALV) long terminal repeat (LTR) in bursal lymphomas and derivative cell lines correspond to a region encompassed by two major hypersensitive sites in the 5' flanking region of the pre-integration, unrearranged c-myc gene. After integration of the ALV LTR, the major hypersensitive site within the avian c-myc oncogene region is within the proviral LTR, and the major hypersensitive sites normally found in uninfected cells 5' to the first c-myc coding exon are no longer detectable.

Animals↗
PubMed2006

Epstein-Barr virus integrates frequently into chromosome 4q, 2q, 1q and 7q of Burkitt's lymphoma cell line (Raji).

Epstein-Barr virus (EBV) integration into a Burkitt's lymphoma (BL) cell line (Raji) was investigated, using polymerase chain reaction (PCR), Southern hybridization, genomic library screening and fluorescence in situ hybridization (FISH). BaMHIW fragments of the EBV genome and DNA sequences of the viral latent membrane protein (LMP)1 and LMP2 genes were detected in Raji cells. BaMHI-digested high-molecular weight DNA from Raji cells generated 4 and 10 kb, 23 kb fragments that hybridized to Probe-1 (EBV genome 13232-16189) and Probe-2 (EBV genome 5-3271). Genomic library for Raji cells was constructed. Plaques (1 x 10(5)) were screened with Probe-2, and four positive clones were obtained. Chromosomal integration of EBV DNA was detected in the Raji cell. The viral integration sites included 1p, 1q, 2q, 3p, 3q, 4q, 5q, 6q, 7p, 7q, 9q, 11p, 14q and 15q. Despite this multiplicity of integration sites, integration showed high frequency only at the sites 4q, 2q, 1q and 7q; 64% of the total signals were found in these four chromosomal bands. No viral integration occurred in chromosomes 16-22 or the sex chromosomes (X, Y). This study is the first comprehensive FISH analysis of EBV integration into the chromosomes of the Raji cell line. The findings support the notion that EBV integrates into the Raji cell genome non-randomly.

Adult↗
PubMed1985

The PLC/PRF/5 human hepatoma cell line. II. Chromosomal assignment of hepatitis B virus integration sites.

The chromosomal sites at which hepatitis B virus (HBV) DNA is integrated into the genome of the hepatocellular carcinoma (HCC) cell line, PLC/PRF/5 were investigated in an attempt to understand the mechanisms by which hepatitis B virus may induce malignant transformation. In situ hybridization of an HBV DNA probe to metaphase chromosomes of the PLC/PRF/5 cell line, followed by statistical analysis, identified three integration sites; these were 15q22-q23, 11q22, and 18q12. In particular, hybridization to chromosome #15, which is present in four copies in complete metaphases of this cell line, was highly significant (p much less than 0.0005).

Adult↗