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 991 records · Page 55Linked to original sources
PubMed1996

Frequency and distribution of chromosomal integration sites of the Epstein-Barr virus genome.

Human lymphocytes can be transformed in vitro by integration of the Epstein-Barr virus (EBV) into the host genome. To study whether integration sites are stable or changeable in the course of long-term cultivation, three EBV-transformed lymphoblastoid cell lines, along with positive control (Namalwa cell line) and negative control (noninfected lymphocytes) cells were studied. A biotinylated Bam H1WEBV-DNA fragment was used as the probe for fluorescence in situ hybridization to count the numbers and to localize the sites of integrated EBV-DNA. Among these cell lines, the percentage of cells with integrated signals varied from 58% to 91%, with a mean of 1.43 to 2.66 signals per cell. No consistent tendency of increasing or decreasing number of signals was observed for the three cell lines harvested at four different cultivation intervals (86-204 days after infection). Although the integration was not site-specific, high frequencies of integration did occur in all three cell lines at the following chromosomal sites: 1p31, 1q31, 2q32, 3q13, 6q24 and 7q31. Because there were multiple integration sites present, it was difficult to draw any conclusion on integration site stability.

Adult↗
PubMed1994

In vitro activities of purified visna virus integrase.

Although integration generally is considered a critical step in the retrovirus life cycle, it has been reported that visna virus, which causes degenerative neurologic disease in sheep, can productively infect sheep choroid plexus cells without detectable integration. To ascertain whether the integrase (IN) of visna virus is an inherently defective enzyme and to create tools for further study of integration of the phylogenetically related human immunodeficiency virus type 1 (HIV-1), we purified visna virus IN by using a bacterial expression system and applied various in vitro oligonucleotide-based assays to studying this protein. We found that visna virus IN demonstrates the full repertoire of in vitro functions characteristic of retroviral integrases. In particular, visna virus IN exhibits site-specific endonuclease activity following the invariant CA found two nucleotides from the 3' ends of viral DNA (processing activity), joins processed oligonucleotides to various sites on other oligonucleotides (strand transfer or integration activity), and reverses the integration reaction by resolving a complex that mimics one end of viral DNA integrated into host DNA (disintegration activity). In addition, although it has been reported that purified HIV-1 IN cannot specifically nick visna virus DNA ends, purified visna virus IN does specifically process and integrate HIV-1 DNA ends.

Base Sequence↗
PubMed1994

A novel diagnostic method of adult T-cell leukemia: monoclonal integration of human T-cell lymphotropic virus type I provirus DNA detected by inverse polymerase chain reaction.

Adult T-cell leukemia (ATL) is neoplasm of the mature helper T lymphocytes and human T-cell lymphotropic virus type-I (HTLV-I) has been shown to be causative virus of ATL. Because HTLV-I integrates its provirus randomly into host chromosomal DNA, monoclonal integration of HTLV-I provirus indicates the clonal proliferation of HTLV-I-infected cells. Therefore, demonstration of clonality of HTLV-I proviral DNA is essential to diagnosis of ATL. Southern blot analysis was used for this purpose. We developed the novel method using inverse polymerase chain reaction (IPCR) to detect the clonality of HTLV-I proviral DNA. This method identified the clonality in all ATL cases. Diagnosis could be made within 3 days using this method. It enabled us to detect specifically the presence of minimal numbers of ATL cells with high sensitivity. It also identified the monoclonal or oligoclonal proliferations of HTLV-I-infected cells in HTLV-I carriers and the intermediate state, in which no clonality could be shown by conventional Southern blot analyses. This finding indicated that even HTLV-I carriers had monoclonal proliferation of HTLV-I-infected cells without any symptoms. This novel method is shown to be useful for the diagnosis of ATL and provides information on the natural course of HTLV-I infection.

Base Sequence↗
PubMedDate not supplied

Three genes with different functions in transformation are regulated by c-Myb in myeloid cells.

The proto-oncogene c-myb is constitutively expressed in murine leukemia virus-induced myeloid leukemia (MML) due to the integration of virus at this locus. Our recent focus has been the determination of genes regulated by this transcription factor that may be involved in transformation. Data presented here, using conditional expression of Myb in myeloid cells, show that c-Myb directly transactivates the endogenous c-myc and Bcl-2 genes, which explains at least in part how c-Myb regulates proliferation and survival. In addition, c-Myb prevents expression at the RNA level of the tumor suppressor INK4b gene. This gene encodes a cyclin-dependent kinase inhibitor, p15INK4b, that is normally upregulated at the mRNA level during myeloid differentiation and promotes growth arrest. The MMLs are generally characterized as differentiated monocytic tumors and possess the phenotype that is normally associated with p15INK4b expression. c-Myb inhibits expression of this gene, however, and therefore acts to promote a pathway which is abnormal in mature cells. This activity of c-Myb collaborates with its maintenance of c-myc expression to promote growth.

Animals↗
PubMed1986

Dynamic and nonspecific dispersal of human T-cell leukemia/lymphoma virus type-I integration in cultured lymphoma cells.

The progression of HTLV-I proviral integration over a 3-year period of in vitro culture was examined in two human lymphoma lines, Hut 102 and MJ. Using specific HTLV-I molecular clones and a Southern analysis at different cell passages, Hut 102 increased from 2 to 19 integrated proviral integrations while MJ increased to at least 25 different integrations by passage 43. During the progress of increased superinfection and novel integration in vitro some of the previous proviral integrations were lost from the cultures. The 19 integrations of late passage Hut 102 cells were shown to be dispersed to 19 different human chromosomes by analysis of 34 distinct rodent X Hut 102 somatic cell hybrids which segregated human chromosomes (and included proviral integrations) in different combinations. The two primary integrations in Hut 102 were located on human chromosomes 4 and 20, respectively. A similar pattern of nonspecific integration was observed in somatic cell hybrid analysis of the 25 proviral integrations of MJ. The dynamic infection-reintegration process in vitro revealed in these studies may confuse experimental verification of potential cis acting functions of HTLV-I in the as yet poorly understood mechanism of neoplastic transformation.

Cell Line↗
PubMed1977

Germ line integration of moloney leukemia virus: effect of homozygosity at the m-mulV locus.

Mice genetically transmitting the exogenous Moloney leukemia virus (M-MuLV) have been previously derived. These animals carried one copy of M-MuLV DNA in their germ line and were heterozygous for the M-MuLV locus (Jaenisch, 1976). Experiments were performed to investigate whether homozygosity at the M-MuLV locus would be compatible with normal development. Animals heterozygous for the M-MuLV locus were mated [female (+/-) X male(+/-)] and the genotype of the offspring was analyzed. Molecular hybridization experiments revealed three classes of offspring carrying two copies (++), one copy (+/-) and no (--) M-MuLV-specific DNA sequences, respectively, in their liver DNA. Genetic experiments indicated that males of the first class transmitted the virus to 100% of their offspring, males of the second class to 50% and males of the third class not at all when mated with normal females. These results demonstrated that homozygosity at the M-MuLV locus has no detectable effect on normal development of the animals and that the M-MuLV gene is transmitted from one generation to the next strictly according to Mendelian expectations. Development of M-MuLV-induced leukemia is not influenced by the genotype of these animals--that is, animals carrying two or one copies of M-MuLV in their germ line or animals congenitally infected from the mother developed disease at similar rates.

Animals↗
PubMed1986

Nucleotide sequence analysis of the long terminal repeat of integrated caprine arthritis encephalitis virus.

The nucleotide sequence of the long terminal repeat (LTR) of caprine arthritis encephalitis virus (CAEV), a prototype lentivirus was determined. 6-bp directly repeated host cell sequences flank the 376-bp proviral LTRs. By comparison with other retroviral sequences, the CAEV LTR likely contains U3, R and U5 regions 207, 86 and 83 base-pairs in length, respectively. Sequences conforming to consensus transcriptional promoter sites were identified in the U3 region upstream of a potential transcription initiation site. A consensus polyadenylation signal is present 20 bases upstream of the putative R-U5 border and a potential poly(A) addition site. Sequence comparisons of the CAEV LTR with those of other retroviruses uncovered significant similarities with that of visna virus. No other global homologies with other retrovirus LTRs could be detected. CAEV utilizes a primer binding site complementary to lysine tRNA as does visna, AIDS associated retroviruses, and mouse mammary tumor virus. The putative primer for positive-strand DNA synthesis identified in the CAEV sequence is identical to that of visna virus and very similar to those of AIDS retroviruses and MMTV. In addition, a stretch that includes the TATA box of the CAEV LTR resembles closely the corresponding region in the AIDS retrovirus. These and other findings further strengthen the classification of AIDS retrovirus as a lentivirus.

Animals↗
PubMed1979

Integration of herpes simplex virus type 1 DNA into the DNA of growth-arrested BHK-21 cells.

The ability of HSV-1 DNA to become associated with host cell DNA in an alkaline-stable form has been demonstrated following infection of a ts baby hamster kidney growth mutant (ts BTN-1), at the non-permissive temperature (39.5 depgrees C). After 8 h pre-incubation at 39.5 degrees C, ts BTN-1 cells infected at this temperature using m.o.i. ranging from 0.5 to 200 p.f.u./cell fail to replicate virus DNA even though transport of input virus genomes to the nucleus is the same at both permissive and non-permissive temperatures. Virions containing 3H-labelled DNA were used to infect ts BTN-1 cells at 39.5 degrees C, and the total cellular DNA isolated from these cells was resolved into host and virus material by repeated CsCl equilibrium gradient centrifugation. A significant amount of the input radioactivity was found as a distinct band in the host region in both neutral and alkaline CsCl gradients, strongly suggesting a covalent association between host and virus DNAs. Evidence for this association was strengthened by demonstrating that radioactive material (virus DNA) banding in the host region of CsCl gradients could be driven towards the density expected for virus DNA following degradation of the putative hybrid molecules by shearing.

Animals↗