Genomes and Genes
Summary: Insertion of viral DNA into host-cell DNA. This includes integration of phage DNA into bacterial DNA; (LYSOGENY); to form a PROPHAGE or integration of retroviral DNA into cellular DNA to form a PROVIRUS.
- Allouch A, Di Primio C, Alpi E, Lusic M, Arosio D, Giacca M, et al. The TRIM family protein KAP1 inhibits HIV-1 integration. Cell Host Microbe. 2011;9:484-95 pubmed publisher..This study identifies KAP1 as a cellular factor restricting HIV-1 infection and underscores the relevance of IN acetylation as a crucial step in the viral infectious cycle. ..
- Gupta S, Maetzig T, Maertens G, Sharif A, Rothe M, Weidner Glunde M, et al. Bromo- and extraterminal domain chromatin regulators serve as cofactors for murine leukemia virus integration. J Virol. 2013;87:12721-36 pubmed publisher..Our data suggest that BET proteins might act as chromatin-bound acceptors for the MLV preintegration complex. These results could pave a way to redirecting MLV DNA integration as a basis for creating safer retroviral vectors. ..
- Mamede J, Sitbon M, Battini J, Courgnaud V. Heterogeneous susceptibility of circulating SIV isolate capsids to HIV-interacting factors. Retrovirology. 2013;10:77 pubmed publisher..Our findings warrant a closer evaluation of other potential defenses against circulating SIV. ..
- Sharma A, Larue R, Plumb M, Malani N, Male F, Slaughter A, et al. BET proteins promote efficient murine leukemia virus integration at transcription start sites. Proc Natl Acad Sci U S A. 2013;110:12036-41 pubmed publisher..These findings elucidate the importance of BET proteins for MLV integration efficiency and targeting and provide a route to developing safer MLV-based vectors for human gene therapy. ..
- Kaufer B, Jarosinski K, Osterrieder N. Herpesvirus telomeric repeats facilitate genomic integration into host telomeres and mobilization of viral DNA during reactivation. J Exp Med. 2011;208:605-15 pubmed publisher..This finding is of particular importance as reactivation is critical for virus spread between susceptible individuals and is necessary for continued herpesvirus evolution and survival. ..
- Ding D, Lou X, Hua D, Yu W, Li L, Wang J, et al. Recurrent targeted genes of hepatitis B virus in the liver cancer genomes identified by a next-generation sequencing-based approach. PLoS Genet. 2012;8:e1003065 pubmed publisher..This global survey of HBV integration events, together with recently published whole-genome sequencing analyses, furthered our understanding of the HBV-related HCC. ..
- Krishnan L, Engelman A. Retroviral integrase proteins and HIV-1 DNA integration. J Biol Chem. 2012;287:40858-66 pubmed publisher..Here, we review recent advances in our knowledge of HIV-1 DNA integration, as well as future research directions...
- Christ F, Shaw S, Demeulemeester J, Desimmie B, Marchand A, Butler S, et al. Small-molecule inhibitors of the LEDGF/p75 binding site of integrase block HIV replication and modulate integrase multimerization. Antimicrob Agents Chemother. 2012;56:4365-74 pubmed publisher..The allosteric nature of inhibition and compatibility with INSTIs underline an interest in further (clinical) development of LEDGINs. ..
- Heckl D, Schwarzer A, Haemmerle R, Steinemann D, Rudolph C, Skawran B, et al. Lentiviral vector induced insertional haploinsufficiency of Ebf1 causes murine leukemia. Mol Ther. 2012;20:1187-95 pubmed publisher..Our results highlight the risk of intragenic vector integration to initiate leukemia by inducing haploinsufficiency of a tumor suppressor gene. We propose to address this risk in future vector design...
- Buzon M, Seiss K, Weiss R, Brass A, Rosenberg E, Pereyra F, et al. Inhibition of HIV-1 integration in ex vivo-infected CD4 T cells from elite controllers. J Virol. 2011;85:9646-50 pubmed publisher..These data contribute to increasing evidence that intrinsic inhibition of specific HIV-1 replication steps plays an important role in the ability of elite controllers to maintain undetectable viral loads. ..
- Aiyer S, Swapna G, Malani N, Aramini J, Schneider W, Plumb M, et al. Altering murine leukemia virus integration through disruption of the integrase and BET protein family interaction. Nucleic Acids Res. 2014;42:5917-28 pubmed publisher..Viruses bearing MLV IN C-terminal truncations can provide new avenues to improve the safety profile of gammaretroviral vectors for human gene therapy. ..
- Schneider W, Brzezinski J, Aiyer S, Malani N, Gyuricza M, Bushman F, et al. Viral DNA tethering domains complement replication-defective mutations in the p12 protein of MuLV Gag. Proc Natl Acad Sci U S A. 2013;110:9487-92 pubmed publisher..Analysis of the integration-site selection of these chimeric viruses showed no significant change in integration profile compared with wild-type MuLV, suggesting release of the tethered p12 post mitosis, before viral integration. ..
- Varshney G, Lu J, Gildea D, Huang H, Pei W, Yang Z, et al. A large-scale zebrafish gene knockout resource for the genome-wide study of gene function. Genome Res. 2013;23:727-35 pubmed publisher..These fish lines establish an important milestone for zebrafish genetics research and should greatly facilitate systematic functional studies of the vertebrate genome. ..
- Elis E, Ehrlich M, Prizan Ravid A, Laham Karam N, Bacharach E. p12 tethers the murine leukemia virus pre-integration complex to mitotic chromosomes. PLoS Pathog. 2012;8:e1003103 pubmed publisher..Altogether, these results explain, in part, MLV restriction to dividing cells and reveal a role for p12 as a factor that tethers MLV PIC to mitotic chromosomes...
- Chen Y, Yao H, Thompson E, Tannir N, Weinstein J, Su X. VirusSeq: software to identify viruses and their integration sites using next-generation sequencing of human cancer tissue. Bioinformatics. 2013;29:266-7 pubmed publisher..Using these data, we showed that VirusSeq accurately detects the known viruses and their integration sites with high sensitivity and specificity. VirusSeq can also perform this function using whole-genome sequencing data of human tissue...
- Zhou L, Sokolskaja E, Jolly C, James W, Cowley S, Fassati A. Transportin 3 promotes a nuclear maturation step required for efficient HIV-1 integration. PLoS Pathog. 2011;7:e1002194 pubmed publisher..The results also provide evidence for a novel tRNA nucleocytoplasmic trafficking pathway in human cells. ..
- De Iaco A, Luban J. Inhibition of HIV-1 infection by TNPO3 depletion is determined by capsid and detectable after viral cDNA enters the nucleus. Retrovirology. 2011;8:98 pubmed publisher..TNPO3 promotes HIV-1 infectivity at a step in the virus life cycle that is detectable after the preintegration complex arrives in the nucleus and CA is the viral determinant for TNPO3 dependence. ..
- Jiang Z, Jhunjhunwala S, Liu J, Haverty P, Kennemer M, Guan Y, et al. The effects of hepatitis B virus integration into the genomes of hepatocellular carcinoma patients. Genome Res. 2012;22:593-601 pubmed publisher..Thus, we report the most comprehensive characterization of HBV integration in hepatocellular carcinoma patients. Such widespread random viral integration will likely increase carcinogenic opportunities in HBV-infected individuals. ..
- Koh Y, Wu X, Ferris A, Matreyek K, Smith S, Lee K, et al. Differential effects of human immunodeficiency virus type 1 capsid and cellular factors nucleoporin 153 and LEDGF/p75 on the efficiency and specificity of viral DNA integration. J Virol. 2013;87:648-58 pubmed publisher..A role for the CA protein in determining the dependency of HIV-1 on LEDGF/p75 during infection highlights a connection between the viral capsid and chromosomal DNA integration. ..
- Santos S, Obukhov Y, Nekhai S, Bukrinsky M, Iordanskiy S. Virus-producing cells determine the host protein profiles of HIV-1 virion cores. Retrovirology. 2012;9:65 pubmed publisher..Incorporation ratio of certain RNA- and DNA-binding proteins suggests their more efficient, non-random packaging into virions in T cells than in mM? and mMN. ..
- Munir S, Thierry S, Subra F, Deprez E, Delelis O. Quantitative analysis of the time-course of viral DNA forms during the HIV-1 life cycle. Retrovirology. 2013;10:87 pubmed publisher..In the latter case, the quantification of 3'-processed DNA in infected cells can be informative about the mechanisms of future integrase inhibitors directly in the cell context. ..
- Ao Z, Jayappa K, Wang B, Zheng Y, Wang X, Peng J, et al. Contribution of host nucleoporin 62 in HIV-1 integrase chromatin association and viral DNA integration. J Biol Chem. 2012;287:10544-55 pubmed publisher..Taken together, these results indicate that the cellular Nup62 is specifically recruited by HIV-1 IN and contribute to an efficient viral DNA integration. ..
- De Rijck J, de Kogel C, Demeulemeester J, Vets S, El Ashkar S, Malani N, et al. The BET family of proteins targets moloney murine leukemia virus integration near transcription start sites. Cell Rep. 2013;5:886-94 pubmed publisher..Together, these data validate BET proteins as MLV integration targeting factors. ..
- Das B, Bischerour J, Barre F. Molecular mechanism of acquisition of the cholera toxin genes. Indian J Med Res. 2011;133:195-200 pubmed..cholerae to integrate its single stranded genome into one, the other, or both V. cholerae chromosomes. Here, we review current knowledge about this smart integration process. ..
- Shan L, Yang H, Rabi S, Bravo H, Shroff N, Irizarry R, et al. Influence of host gene transcription level and orientation on HIV-1 latency in a primary-cell model. J Virol. 2011;85:5384-93 pubmed publisher..Our findings suggest that disrupting the negative control of HIV-1 transcription by upstream host promoters could facilitate the reactivation of latent HIV-1 in some resting CD4(+) T cells. ..
- Craigie R, Bushman F. HIV DNA integration. Cold Spring Harb Perspect Med. 2012;2:a006890 pubmed publisher..Models for some of the molecular mechanisms involved have been proposed, but important details remain to be clarified. ..
- Aubert M, Ryu B, Banks L, Rawlings D, Scharenberg A, Jerome K. Successful targeting and disruption of an integrated reporter lentivirus using the engineered homing endonuclease Y2 I-AniI. PLoS ONE. 2011;6:e16825 pubmed publisher..This new technology offers the possibility of selectively disabling integrated HIV provirus within latently infected cells. ..
- Li J, Wan R, Yu C, Co N, Wong N, Chan T. ViralFusionSeq: accurately discover viral integration events and reconstruct fusion transcripts at single-base resolution. Bioinformatics. 2013;29:649-51 pubmed publisher..Our experiments demonstrated that VFS is both sensitive and highly accurate. VFS is distributed under GPL version 3 at http://hkbic.cuhk.edu.hk/software/viralfusionseq ..
- Schweitzer C, Jagadish T, Haverland N, Ciborowski P, Belshan M. Proteomic analysis of early HIV-1 nucleoprotein complexes. J Proteome Res. 2013;12:559-72 pubmed publisher..This study contributes additional novel candidate proteins to the growing published bioinformatic data sets of proteins that contribute to HIV-1 replication. ..
- Yoder K, Espeseth A, Wang X, Fang Q, Russo M, Lloyd R, et al. The base excision repair pathway is required for efficient lentivirus integration. PLoS ONE. 2011;6:e17862 pubmed publisher..Integration activity is restored by addition of recombinant BER protein POLß. Lentiviral infection and integration efficiency appears to depend on the presence of BER proteins. ..
- Sakkhachornphop S, Barbas C, Keawvichit R, Wongworapat K, Tayapiwatana C. Zinc finger protein designed to target 2-long terminal repeat junctions interferes with human immunodeficiency virus integration. Hum Gene Ther. 2012;23:932-42 pubmed publisher..We suggest that the expression of 2LTRZFP-GFP limited viral integration on intracellular immunization, and that it has potential for use in HIV gene therapy in the future. ..
- Pandey K, Bera S, Grandgenett D. The HIV-1 integrase monomer induces a specific interaction with LTR DNA for concerted integration. Biochemistry. 2011;50:9788-96 pubmed publisher..The HIV IN monomer may be a suitable candidate for attempting crystallization of an IN-DNA complex in the absence or presence of strand transfer inhibitors. ..
- Tsuruyama T, Liu W, Yoshikawa K. In vitro murine leukemia retroviral integration and structure fluctuation of target DNA. PLoS ONE. 2012;7:e31533 pubmed publisher..The approach described here can provide data on the biochemical properties of the integration reaction to which the target DNA structure may contribute. ..
- Jiang S, Yang Z, Li W, Li X, Wang Y, Zhang J, et al. Re-evaluation of the carcinogenic significance of hepatitis B virus integration in hepatocarcinogenesis. PLoS ONE. 2012;7:e40363 pubmed publisher..The frequency and patterns of HBV insertions were similar between tumor and their adjacent non-tumor samples indicating that the majority of HBV DNA integration events are not associated with hepatocarcinogenesis...
- da Silveira G, Oliveira Costa J, Soave D, Zanetti J, Soares F, Ribeiro Silva A. Relationship between B-cell-specific Moloney murine leukemia virus integration site 1 (BMI-1) and homologous recombination regulatory genes in invasive ductal breast carcinomas. Histol Histopathol. 2012;27:1353-9 pubmed publisherB-cell-specific Moloney murine leukemia virus integration site 1 (Bmi-1) is a Polycomb group protein that is able to induce telomerase activity, enabling the immortalization of epithelial cells...
- Wang H, Jurado K, Wu X, Shun M, Li X, Ferris A, et al. HRP2 determines the efficiency and specificity of HIV-1 integration in LEDGF/p75 knockout cells but does not contribute to the antiviral activity of a potent LEDGF/p75-binding site integrase inhibitor. Nucleic Acids Res. 2012;40:11518-30 pubmed publisher..These findings help to rule out the host factor-IN interactions as the primary antiviral targets of LEDGF/p75-binding site IN inhibitors. ..
- Biffi A, Bartolomae C, Cesana D, Cartier N, Aubourg P, Ranzani M, et al. Lentiviral vector common integration sites in preclinical models and a clinical trial reflect a benign integration bias and not oncogenic selection. Blood. 2011;117:5332-9 pubmed publisher..These findings imply that LV CISs are produced by an integration bias toward specific genomic regions rather than by oncogenic selection. ..
- Sung W, Zheng H, Li S, Chen R, Liu X, Li Y, et al. Genome-wide survey of recurrent HBV integration in hepatocellular carcinoma. Nat Genet. 2012;44:765-9 pubmed publisher..We also report evidence that suggests that the number of HBV integrations is associated with patient survival. ..
- Fricke T, Valle Casuso J, White T, Brandariz Nuñez A, Bosche W, Reszka N, et al. The ability of TNPO3-depleted cells to inhibit HIV-1 infection requires CPSF6. Retrovirology. 2013;10:46 pubmed publisher..Fate of the capsid assays revealed that cytosolic expression of CPSF6 enhances stability of the HIV-1 core during infection. These results suggested that inhibition of HIV-1 by TNPO3-depleted cells requires CPSF6. ..
- De Luca L, Gitto R, Christ F, Ferro S, De Grazia S, Morreale F, et al. 4-[1-(4-Fluorobenzyl)-4-hydroxy-1H-indol-3-yl]-2-hydroxy-4-oxobut-2-enoic acid as a prototype to develop dual inhibitors of HIV-1 integration process. Antiviral Res. 2011;92:102-7 pubmed publisher..This work has suggested the possibility of also constructing an integration dual inhibitor using a design-in strategy. ..
- Schneider W, Wu D, Amin V, Aiyer S, Roth M. MuLV IN mutants responsive to HDAC inhibitors enhance transcription from unintegrated retroviral DNA. Virology. 2012;426:188-96 pubmed publisher..The MuLV IN protein is acetylated by p300 in vitro, however, the effect of HDAC inhibitors on gene expression from unintegrated DNA is not dependent on the acetylation state of MuLV IN K376. ..
- Espeseth A, Fishel R, Hazuda D, Huang Q, Xu M, Yoder K, et al. siRNA screening of a targeted library of DNA repair factors in HIV infection reveals a role for base excision repair in HIV integration. PLoS ONE. 2011;6:e17612 pubmed publisher..Examining the role BER enzymes play in HIV infection suggests a role for the BER pathway in HIV integration. ..
- Mexas A, Graf E, Pace M, Yu J, Papasavvas E, Azzoni L, et al. Concurrent measures of total and integrated HIV DNA monitor reservoirs and ongoing replication in eradication trials. AIDS. 2012;26:2295-306 pubmed publisher..We conclude that concurrent measurements of total and integrated HIV DNA provide information regarding reservoir size and ongoing replication in trials targeting HIV. ..
- Tsiang M, Jones G, Niedziela Majka A, Kan E, Lansdon E, Huang W, et al. New class of HIV-1 integrase (IN) inhibitors with a dual mode of action. J Biol Chem. 2012;287:21189-203 pubmed publisher..For the first time, tBPQAs were demonstrated to be allosteric inhibitors of HIV-1 IN displaying a dual mode of action: inhibition of IN-viral DNA assembly and inhibition of IN-LEDGF interaction...
- Ebina H, Kanemura Y, Suzuki Y, Urata K, Misawa N, Koyanagi Y. Integrase-independent HIV-1 infection is augmented under conditions of DNA damage and produces a viral reservoir. Virology. 2012;427:44-50 pubmed publisher..Altogether, our results suggest that HIV DNA has integration potential in the presence of an IN inhibitor and may serve as a virus reservoir. ..
- Hare S, Maertens G, Cherepanov P. 3'-processing and strand transfer catalysed by retroviral integrase in crystallo. EMBO J. 2012;31:3020-8 pubmed publisher..The ground state structures moreover highlight a striking substrate mimicry utilized by the inhibitors in their binding to the IN active site and suggest ways to improve upon this clinically relevant class of small molecules...
- Khaleel T, Younger E, McEwan A, Varghese A, Smith M. A phage protein that binds ?C31 integrase to switch its directionality. Mol Microbiol. 2011;80:1450-63 pubmed publisher..The functional properties of ?C31 gp3 resemble those of the evolutionarily unrelated RDF from phage Bxb1, suggesting that these two RDFs have arisen through convergent evolution...