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Nature Reviews. Genetics May 2017Transposable elements and retroviruses are found in most genomes, can be pathogenic and are widely used as gene-delivery and functional genomics tools. Exploring whether... (Review)
Review
Transposable elements and retroviruses are found in most genomes, can be pathogenic and are widely used as gene-delivery and functional genomics tools. Exploring whether these genetic elements target specific genomic sites for integration and how this preference is achieved is crucial to our understanding of genome evolution, somatic genome plasticity in cancer and ageing, host-parasite interactions and genome engineering applications. High-throughput profiling of integration sites by next-generation sequencing, combined with large-scale genomic data mining and cellular or biochemical approaches, has revealed that the insertions are usually non-random. The DNA sequence, chromatin and nuclear context, and cellular proteins cooperate in guiding integration in eukaryotic genomes, leading to a remarkable diversity of insertion site distribution and evolutionary strategies.
Topics: Animals; DNA Transposable Elements; Eukaryota; Evolution, Molecular; Genetic Variation; Genome, Viral; Genomics; Humans; Retroviridae; Virus Integration
PubMed: 28286338
DOI: 10.1038/nrg.2017.7 -
Advances in Genetics 2005Integration of retroviral cDNA into the host cell chromosome is an essential step in its replication. This process is catalyzed by the retroviral integrase protein,... (Review)
Review
Integration of retroviral cDNA into the host cell chromosome is an essential step in its replication. This process is catalyzed by the retroviral integrase protein, which is conserved among retroviruses and retrotransposons. Integrase binds viral and host DNA in a complex, called the preintegration complex (PIC), with other viral and cellular proteins. While the PIC is capable of directing integration of the viral DNA into any chromosomal location, different retroviruses have clear preferences for integration in or near particular chromosomal features. The determinants of integration site selection are under investigation but may include retrovirus-specific interactions between integrase and tethering factors bound to the host cell chromosomes. Research into the mechanisms of retroviral integration site selection has shed light on the phenomena of insertional mutagenesis and viral latency.
Topics: DNA; Integrases; Models, Molecular; Mutagenesis, Insertional; Retroviridae; Virus Integration
PubMed: 16291214
DOI: 10.1016/S0065-2660(05)55005-3 -
BMB Reports Apr 2012Retroviruses have often been used for gene therapy because of their capacity for the long-term expression of transgenes via stable integration into the host genome.... (Review)
Review
Retroviruses have often been used for gene therapy because of their capacity for the long-term expression of transgenes via stable integration into the host genome. However, retroviral integration can also result in the transformation of normal cells into cancer cells, as demonstrated by the incidence of leukemia in a recent retroviral gene therapy trial in Europe. This unfortunate outcome has led to the rapid initiation of studies examining various biological and pathological aspects of retroviral integration. This review summarizes recent findings from these studies, including the global integration patterns of various types of retroviruses, viral and cellular determinants of integration, implications of integration for gene therapy and retrovirus-mediated infectious diseases, and strategies to shift integration to safe host genomic loci. A more comprehensive and mechanistic understanding of retroviral integration processes will eventually make it possible to generate safer retroviral vector platforms in the near future.
Topics: Genetic Therapy; Genetic Vectors; Humans; Retroviridae; Virus Integration
PubMed: 22531129
DOI: 10.5483/bmbrep.2012.45.4.207 -
Sub-cellular Biochemistry 2018The retrovirus capsid core is a metastable structure that disassembles during the early phase of viral infection after membrane fusion. The core is intact and permeable... (Review)
Review
The retrovirus capsid core is a metastable structure that disassembles during the early phase of viral infection after membrane fusion. The core is intact and permeable to essential nucleotides during reverse transcription, but it undergoes disassembly for nuclear entry and genome integration. Increasing or decreasing the stability of the capsid core has a substantial negative impact on virus infectivity, which makes the core an attractive anti-viral target. The retrovirus capsid core also encounters a variety of virus- and organism-specific host cellular factors that promote or restrict viral replication. This review describes the structural elements fundamental to the formation and stability of the capsid core. The physical and chemical properties of the capsid core that are critical to its functional role in reverse transcription and interaction with host cellular factors are highlighted to emphasize areas of current research.
Topics: Animals; Capsid; Humans; Retroviridae; Reverse Transcription; Virus Integration; Virus Internalization; Virus Replication
PubMed: 29900497
DOI: 10.1007/978-981-10-8456-0_8 -
PLoS Pathogens Apr 2017
Review
Topics: Humans; Neoplasms; Papillomaviridae; Papillomavirus Infections; Virus Integration
PubMed: 28384274
DOI: 10.1371/journal.ppat.1006211 -
Trends in Biochemical Sciences Feb 2006To achieve productive infection, the reverse transcribed cDNA of human immunodeficiency virus type 1 (HIV-1) is inserted in the host cell genome. The main protein... (Review)
Review
To achieve productive infection, the reverse transcribed cDNA of human immunodeficiency virus type 1 (HIV-1) is inserted in the host cell genome. The main protein responsible for this reaction is the viral integrase. However, studies indicate that the virus is assisted by cellular proteins, or co-factors, to achieve integration into the infected cell. The barrier-to-autointegration factor (BAF) might prevent autointegration. Its ability to bridge DNA and the finding that the nuclear lamina-associated polypeptide-2alpha interacts with BAF suggest a role in nuclear structure organization. Integrase interactor 1 was found to directly interact with HIV-1 integrase and to activate its DNA-joining activity, and the high mobility group chromosomal protein A1 might approximate both long terminal repeat (LTR) ends and facilitate integrase binding by unwinding the LTR termini. Furthermore, the lens-epithelium-derived growth factor (LEDGF; also known as p75) seems to tether HIV-1 integrase to the chromosomes. Although a direct role in integration has only been demonstrated for LEDGF/p75, to date, each validated cellular co-factor for HIV-1 integration could constitute a promising new target for antiviral therapy.
Topics: Animals; Chromosomal Proteins, Non-Histone; DNA, Viral; DNA-Binding Proteins; HIV Integrase; HIV-1; HMGA1a Protein; Humans; Intercellular Signaling Peptides and Proteins; Membrane Proteins; Nuclear Proteins; SMARCB1 Protein; Transcription Factors; Virus Integration
PubMed: 16403635
DOI: 10.1016/j.tibs.2005.12.002 -
Proceedings of the National Academy of... Apr 2005To investigate retroviral integration targeting on a nucleotide scale, we examined the base frequencies directly surrounding cloned in vivo HIV-1, murine leukemia virus,... (Comparative Study)
Comparative Study
To investigate retroviral integration targeting on a nucleotide scale, we examined the base frequencies directly surrounding cloned in vivo HIV-1, murine leukemia virus, and avian sarcoma/leukosis virus integrations. Base preferences of up to 2-fold the expected frequencies were found for three viruses, representing P values down to <10(-100) and defining what appear to be preferred integration sequences. Offset symmetry reflecting the topology of the integration reaction was found for HIV-1 and avian sarcoma/leukosis virus but not murine leukemia virus, suggesting fundamental differences in the way different retroviral integration complexes interact with host-cell DNA.
Topics: Alpharetrovirus; Base Composition; Base Sequence; Cloning, Molecular; HIV-1; HeLa Cells; Humans; Virus Integration
PubMed: 15802467
DOI: 10.1073/pnas.0501646102 -
Medecine Sciences : M/S Feb 2016Recombinant AAV vectors (rAAV) are considered as very efficient tools for in vivo gene transfer. Accordingly, several preclinical and clinical gene therapy trials use... (Review)
Review
Recombinant AAV vectors (rAAV) are considered as very efficient tools for in vivo gene transfer. Accordingly, several preclinical and clinical gene therapy trials use these vectors to treat inherited and acquired diseases. rAAV vectors possess the capacity to persist for a long term in the transduced tissue in a transcriptionally active, extra-chromosomal (episomal) form. However, many studies have shown that a significant fraction of the rAAV genomes can also nonspecifically integrate into the host cell genome thus raising the possibility of insertional mutagenesis events. This review summarizes the current knowledge on integration of wild type and rAAV genomes and highlights the major questions which remain unresolved.
Topics: Animals; DNA, Viral; Dependovirus; Gene Transfer Techniques; Genetic Therapy; Genetic Vectors; Genome, Viral; Humans; Mutagenesis, Insertional; Recombination, Genetic; Virus Integration
PubMed: 26936174
DOI: 10.1051/medsci/20163202010 -
BMC Genomics Oct 2004Plant genomes contain various kinds of repetitive sequences such as transposable elements, microsatellites, tandem repeats and virus-like sequences. Most of them, with...
BACKGROUND
Plant genomes contain various kinds of repetitive sequences such as transposable elements, microsatellites, tandem repeats and virus-like sequences. Most of them, with the exception of virus-like sequences, do not allow us to trace their origins nor to follow the process of their integration into the host genome. Recent discoveries of virus-like sequences in plant genomes led us to set the objective of elucidating the origin of the repetitive sequences. Endogenous rice tungro bacilliform virus (RTBV)-like sequences (ERTBVs) have been found throughout the rice genome. Here, we reconstructed putative virus structures from RTBV-like sequences in the rice genome and characterized to understand evolutionary implication, integration manner and involvements of endogenous virus segments in the corresponding disease response.
RESULTS
We have collected ERTBVs from the rice genomes. They contain rearranged structures and no intact ORFs. The identified ERTBV segments were shown to be phylogenetically divided into three clusters. For each phylogenetic cluster, we were able to make a consensus alignment for a circular virus-like structure carrying two complete ORFs. Comparisons of DNA and amino acid sequences suggested the closely relationship between ERTBV and RTBV. The Oryza AA-genome species vary in the ERTBV copy number. The species carrying low-copy-number of ERTBV segments have been reported to be extremely susceptible to RTBV. The DNA methylation state of the ERTBV sequences was correlated with their copy number in the genome.
CONCLUSIONS
These ERTBV segments are unlikely to have functional potential as a virus. However, these sequences facilitate to establish putative virus that provided information underlying virus integration and evolutionary relationship with existing virus. Comparison of ERTBV among the Oryza AA-genome species allowed us to speculate a possible role of endogenous virus segments against its related disease.
Topics: Amino Acid Sequence; Badnavirus; DNA Methylation; DNA Viruses; DNA, Plant; DNA, Viral; Evolution, Molecular; Genome, Plant; Molecular Sequence Data; Oryza; Phylogeny; Species Specificity; Virus Integration
PubMed: 15488154
DOI: 10.1186/1471-2164-5-80 -
Trends in Immunology Jun 2022Several viruses hide in the genome of their host. To complete their replication cycle, they need to integrate in the form of a provirus and express their genes. In... (Review)
Review
Several viruses hide in the genome of their host. To complete their replication cycle, they need to integrate in the form of a provirus and express their genes. In vertebrates, integrated viruses can be silenced by chromatin, implying that some specific mechanisms exist to detect non-self genes. The known mechanisms depend on sequence features of retroelements, but the fluctuations of virus expression suggest that other determinants also exist. Here we review the mechanisms allowing chromatin to silence integrated viruses and propose that DNA repair may help flag them as 'non-self' shortly after their genomic insertion.
Topics: Animals; Chromatin; Gene Silencing; Humans; Proviruses; Virus Integration
PubMed: 35490134
DOI: 10.1016/j.it.2022.04.003