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Head & Neck Feb 2002Little has been known about whether Epstein-Barr virus (EBV) could persist in nasopharyngeal carcinoma (NPC) cells by chromosomal integration, and no NPC cell line...
BACKGROUND
Little has been known about whether Epstein-Barr virus (EBV) could persist in nasopharyngeal carcinoma (NPC) cells by chromosomal integration, and no NPC cell line harboring integrated EBV has been reported. In this study, we explored this issue through isolating EBV-infected NPC cell clones generated from an in vitro infection system and examining the configuration of EBV DNA in these cells.
METHODS AND RESULTS
EBV genomes were demonstrated in NPC cell clones using polymerase chain reaction and Southern hybridization. Viral nuclear antigens were also detected by use of an anticomplement immunofluorescence assay and an immunoblotting assay. Gardella gel analysis showed that two of the EBV-positive cell clones, H2B4 and H2B17-7, harbored no extrachromosomal form of the viral genome. Restriction analysis of EBV genomic termini indicated that EBV DNA in these two cell clones was not circularized, and the viral genomes were integrated into chromosomes as demonstrated by fluorescence in situ hybridization.
CONCLUSIONS
This is the first in vitro model of EBV persistence in NPC cells by genomic integration, which represents a unique state of virus-cell interaction. Using this model, investigation into the association between EBV integration and chromosomal abnormality in tumor cells will help to reveal the underlying biologic significance.
Topics: Carcinoma; Genetic Vectors; Genome, Viral; Herpesvirus 4, Human; Humans; In Vitro Techniques; Nasopharyngeal Neoplasms; Tumor Cells, Cultured; Virus Integration
PubMed: 11891944
DOI: 10.1002/hed.10039 -
Cells Feb 2022HIV-1 integrase and capsid proteins interact with host proteins to direct preintegration complexes to active transcription units within gene-dense regions of chromosomes...
HIV-1 integrase and capsid proteins interact with host proteins to direct preintegration complexes to active transcription units within gene-dense regions of chromosomes for viral DNA integration. Analyses of spatially-derived genomic DNA coordinates, such as nuclear speckle-associated domains, lamina-associated domains, super enhancers, and Spatial Position Inference of the Nuclear (SPIN) genome states, have further informed the mechanisms of HIV-1 integration targeting. Critically, however, these different types of genomic coordinates have not been systematically analyzed to synthesize a concise description of the regions of chromatin that HIV-1 prefers for integration. To address this informational gap, we have extensively correlated genomic DNA coordinates of HIV-1 integration targeting preferences. We demonstrate that nuclear speckle-associated and speckle-proximal chromatin are highly predictive markers of integration and that these regions account for known HIV biases for gene-dense regions, highly transcribed genes, as well as the mid-regions of gene bodies. In contrast to a prior report that intronless genes were poorly targeted for integration, we find that intronless genes in proximity to nuclear speckles are more highly targeted than are spatially-matched intron-containing genes. Our results additionally highlight the contributions of capsid and integrase interactions with respective CPSF6 and LEDGF/p75 host factors in these HIV-1 integration targeting preferences.
Topics: Capsid; Capsid Proteins; Chromatin; HIV-1; Host-Pathogen Interactions; Virus Integration
PubMed: 35203306
DOI: 10.3390/cells11040655 -
Biochimica Et Biophysica Acta 2010Since integration into the host cell genome is an obligatory step for their replication, retro-elements are both potent insertional mutagens and also suitable vectors... (Review)
Review
Since integration into the host cell genome is an obligatory step for their replication, retro-elements are both potent insertional mutagens and also suitable vectors for gene therapy. Many recent studies reported that the integration process is not random but, on the contrary, higly regulated at the molecular level. Many viral proteins and cellular factors play a key role in the integration step, explaining the reason why different retro-elements display distinct integration profiles. This review describes the recent highlights about integration of retro-elements with particular focus on the mechanisms underlying the specificity of integration target-site selection and the step of chromosomal tethering which preceeds insertion of the provirus.
Topics: Chromosomes, Human; HIV-1; Humans; Lentivirus; Retroelements; Virus Integration; Virus Replication
PubMed: 19683084
DOI: 10.1016/j.bbagrm.2009.08.005 -
The Journal of Clinical Investigation Feb 2016A substantial research effort has been directed to identifying strategies to eradicate or control HIV infection without a requirement for combination antiretroviral... (Review)
Review
A substantial research effort has been directed to identifying strategies to eradicate or control HIV infection without a requirement for combination antiretroviral therapy (cART). A number of obstacles prevent HIV eradication, including low-level viral persistence during cART, long-term persistence of HIV-infected cells, and latent infection of resting CD4+ T cells. Mechanisms of persistence remain uncertain, but integration of the provirus into the host genome represents a central event in replication and pathogenesis of all retroviruses, including HIV. Analysis of HIV proviruses in CD4+ lymphocytes from individuals after prolonged cART revealed that a substantial proportion of the infected cells that persist have undergone clonal expansion and frequently have proviruses integrated in genes associated with regulation of cell growth. These data suggest that integration may influence persistence and clonal expansion of HIV-infected cells after cART is introduced, and these processes may represent key mechanisms for HIV persistence. Determining the diversity of host genes with integrants in HIV-infected cells that persist for prolonged periods may yield useful information regarding pathways by which infected cells persist for prolonged periods. Moreover, many integrants are defective, and new studies are required to characterize the role of clonal expansion in the persistence of replication-competent HIV.
Topics: Animals; Anti-Retroviral Agents; CD4-Positive T-Lymphocytes; HIV Infections; HIV-1; Humans; Proviruses; Virus Integration
PubMed: 26829624
DOI: 10.1172/JCI80564 -
Journal of Virology Feb 2008Two similar, large double-stranded DNA viruses, Feldmannia species virus 158 (FsV-158) and FsV-178, replicate only in the unilocular reproductive cells (sporangia) of a...
Two similar, large double-stranded DNA viruses, Feldmannia species virus 158 (FsV-158) and FsV-178, replicate only in the unilocular reproductive cells (sporangia) of a brown filamentous alga in the genus Feldmannia. Virus particles are not present in vegetative cells but they are produced in the sporangia formed on vegetative filaments that have been transferred newly into culture. Thus, we proposed that these viruses exist in the vegetative cells in a latent form (R. G. Ivey, E. C. Henry, A. M. Lee, L. Klepper, S. K. Krueger, and R. H. Meints, Virology 220:267-273, 1996). In this article we present evidence that the two FsV genomes are integrated into the host genome during vegetative growth. The FsV genome integration sites were identified by cloning the regions where the FsV genome is linked to the host DNA. FsV-158 and FsV-178 are integrated into two distinct locations in the algal genome. In contrast, the integration sites in the two viral genomes are identical. Notably, the integration sites in the host and viruses contain GC and CG dinucleotide sequences, respectively, from which the GC sequences are recovered at both host-virus junctions. The splice sites in the two FsV genomes are predicted to form a stem-loop structure with the CG dinucleotide in the loop portion.
Topics: Chromosomes; DNA, Algal; DNA, Viral; Phaeophyceae; Phycodnaviridae; Virus Integration
PubMed: 18032486
DOI: 10.1128/JVI.01983-07 -
Epidemiologie, Mikrobiologie,... Sep 2012Two closely related and commonly found human herpesviruses HHV-6 A and HHV-6 B are classified into the sixth human herpes virus complex (HHV-6). Primary infection with... (Review)
Review
Two closely related and commonly found human herpesviruses HHV-6 A and HHV-6 B are classified into the sixth human herpes virus complex (HHV-6). Primary infection with HHV-6 often takes place in early childhood and it can be either asymptomatic or manifests itself as sixth disease (caused by HHV-6 B). HHV-6 remains present in a latent form in the body with the potential for virus reactivation. The article points out the phenomenon of chromosomal integration of HHV-6 (Ci-HHV-6) which is found in about 1% of the population and, unlike the commonly spread HHV-6 infection, has become hereditary, with its pathological potential in Ci-HHV-6 DNA carriers remaining unknown. Therefore, the focus on clinical consequences of Ci-HHV-6 is of high relevance to the therapeutic strategy for patients with high HHV-6 positivity in molecular biological tests.
Topics: Carrier State; Exanthema Subitum; Herpesvirus 6, Human; Humans; Virus Integration
PubMed: 23173298
DOI: No ID Found -
European Journal of Cancer (Oxford,... Jul 2016Fifteen percent of cancers are driven by oncogenic human viruses. Four of those viruses, hepatitis B virus, human papillomavirus, Merkel cell polyomavirus, and human... (Review)
Review
Fifteen percent of cancers are driven by oncogenic human viruses. Four of those viruses, hepatitis B virus, human papillomavirus, Merkel cell polyomavirus, and human T-cell lymphotropic virus, integrate the host genome. Viral oncogenesis is the result of epigenetic and genetic alterations that happen during viral integration. So far, little data have been available regarding integration mechanisms and modifications in the host genome. However, the emergence of high-throughput sequencing and bioinformatic tools enables researchers to establish the landscape of genomic alterations and predict the events that follow viral integration. Cooperative working groups are currently investigating these factors in large data sets. Herein, we provide novel insights into the initiating events of cancer onset during infection with integrative viruses. Although much remains to be discovered, many improvements are expected from the clinical point of view, from better prognosis classifications to better therapeutic strategies.
Topics: Computational Biology; Genome, Viral; Genomics; High-Throughput Nucleotide Sequencing; Humans; Neoplasms; Oncogenic Viruses; Virus Diseases; Virus Integration
PubMed: 27156225
DOI: 10.1016/j.ejca.2016.03.086 -
Journal of Virology Sep 2022
Topics: Chromosomes; DNA, Viral; Hematologic Neoplasms; Herpesvirus 6, Human; Humans; Roseolovirus Infections; Virus Integration
PubMed: 36005759
DOI: 10.1128/jvi.00937-22 -
PloS One Apr 2010Xenotropic murine leukemia virus (MLV)-related virus (XMRV) is a new human retrovirus associated with prostate cancer and chronic fatigue syndrome. The causal...
Xenotropic murine leukemia virus (MLV)-related virus (XMRV) is a new human retrovirus associated with prostate cancer and chronic fatigue syndrome. The causal relationship of XMRV infection to human disease and the mechanism of pathogenicity have not been established. During retrovirus replication, integration of the cDNA copy of the viral RNA genome into the host cell chromosome is an essential step and involves coordinated joining of the two ends of the linear viral DNA into staggered sites on target DNA. Correct integration produces proviruses that are flanked by a short direct repeat, which varies from 4 to 6 bp among the retroviruses but is invariant for each particular retrovirus. Uncoordinated joining of the two viral DNA ends into target DNA can cause insertions, deletions, or other genomic alterations at the integration site. To determine the fidelity of XMRV integration, cells infected with XMRV were clonally expanded and DNA sequences at the viral-host DNA junctions were determined and analyzed. We found that a majority of the provirus ends were correctly processed and flanked by a 4-bp direct repeat of host DNA. A weak consensus sequence was also detected at the XMRV integration sites. We conclude that integration of XMRV DNA involves a coordinated joining of two viral DNA ends that are spaced 4 bp apart on the target DNA and proceeds with high fidelity.
Topics: Cell Line; DNA, Viral; Fatigue Syndrome, Chronic; Female; Humans; Leukemia Virus, Murine; Male; Prostatic Neoplasms; Retroviridae Infections; Sequence Analysis, DNA; Tumor Virus Infections; Virus Integration
PubMed: 20421928
DOI: 10.1371/journal.pone.0010255 -
Cell Host & Microbe May 2016Viral latency can be considered a metastable, nonproductive infection state that is capable of subsequent reactivation to repeat the infection cycle. Viral latent... (Review)
Review
Viral latency can be considered a metastable, nonproductive infection state that is capable of subsequent reactivation to repeat the infection cycle. Viral latent infections have numerous associated pathologies, including cancer, birth defects, neuropathy, cardiovascular disease, chronic inflammation, and immunological dysfunctions. The mechanisms controlling the establishment, maintenance, and reactivation from latency are complex and diversified among virus families, species, and strains. Yet, as examined in this review, common properties of latent viral infections can be defined. Eradicating latent virus has become an important but elusive challenge and will require a more complete understanding of the mechanisms controlling these processes.
Topics: Animals; DNA Viruses; Epigenesis, Genetic; Genes, Viral; Herpesvirus 1, Human; Humans; Virus Diseases; Virus Integration; Virus Latency; Virus Physiological Phenomena; Virus Replication
PubMed: 27173930
DOI: 10.1016/j.chom.2016.04.008