Genomes and Genes
Gene Symbol: gag-pol
Alias: Gag-Pol polyprotein
Species: Human immunodeficiency virus 1
Publications104 found, 100 shown here
- Ludwig C, Leiherer A, Wagner R. Importance of protease cleavage sites within and flanking human immunodeficiency virus type 1 transframe protein p6* for spatiotemporal regulation of protease activation. J Virol. 2008;82:4573-84 pubmed publisher..In sum, we conclude that p6* cleavage is absolutely essential to allow complete activation of the PR and subsequent processing of the viral precursors. ..
- Kleiman L, Jones C, Musier Forsyth K. Formation of the tRNALys packaging complex in HIV-1. FEBS Lett. 2010;584:359-65 pubmed publisher..The molecular interactions that direct assembly of the tRNA(Lys)/LysRS packaging complex hold promise for the development of new anti-viral agents. ..
- Lesbats P, Botbol Y, Chevereau G, Vaillant C, Calmels C, Arneodo A, et al. Functional coupling between HIV-1 integrase and the SWI/SNF chromatin remodeling complex for efficient in vitro integration into stable nucleosomes. PLoS Pathog. 2011;7:e1001280 pubmed publisher..Our data indicate that some chromatin structures can be refractory for integration and that coupling between nucleosome remodeling and HIV-1 integration is required to overcome this natural barrier. ..
- Jayappa K, Ao Z, Yao X. The HIV-1 passage from cytoplasm to nucleus: the process involving a complex exchange between the components of HIV-1 and cellular machinery to access nucleus and successful integration. Int J Biochem Mol Biol. 2012;3:70-85 pubmed..Hereby we aim to further our understanding on molecular mechanism of HIV-1 nuclear import and its potential usefulness for anti-HIV-1 strategies. ..
- Yang Y, Fricke T, Diaz Griffero F. Inhibition of reverse transcriptase activity increases stability of the HIV-1 core. J Virol. 2013;87:683-7 pubmed publisher..Collectively, this work implies that the surface of the HIV-1 core is dynamic and changes upon the ongoing processes within the core. ..
- Busschots K, Voet A, De Maeyer M, Rain J, Emiliani S, Benarous R, et al. Identification of the LEDGF/p75 binding site in HIV-1 integrase. J Mol Biol. 2007;365:1480-92 pubmed..Comparison of the wild-type IN-LEDGF/p75 co-crystal structure with that of the modelled structure of the IN(Q168A) and IN(W131A) mutant integrases corroborated our experimental data. ..
- Lemay J, Maidou Peindara P, Bader T, Ennifar E, Rain J, Benarous R, et al. HuR interacts with human immunodeficiency virus type 1 reverse transcriptase, and modulates reverse transcription in infected cells. Retrovirology. 2008;5:47 pubmed publisher..These results suggest that HuR may be involved in and may modulate the reverse transcription reaction of HIV-1, by an as yet unknown mechanism involving a protein-protein interaction with HIV-1 RT. ..
- Sorin M, Cano J, Das S, Mathew S, Wu X, Davies K, et al. Recruitment of a SAP18-HDAC1 complex into HIV-1 virions and its requirement for viral replication. PLoS Pathog. 2009;5:e1000463 pubmed publisher..Furthermore, HIV-1 virion-associated HDAC1 is required for efficient early post-entry events, indicating a novel role for HDAC1 during HIV-1 replication. ..
- Nishitsuji H, Hayashi T, Takahashi T, Miyano M, Kannagi M, Masuda T. Augmentation of reverse transcription by integrase through an interaction with host factor, SIP1/Gemin2 Is critical for HIV-1 infection. PLoS ONE. 2009;4:e7825 pubmed publisher..Taken together, SIP1 appears to stabilize functional multimer forms of IN, thereby promoting the assembly of IN and RT on viral RNA to allow efficient reverse transcription, which is a prerequisite for efficient HIV-1 infection. ..
- Allouch A, Cereseto A. Identification of cellular factors binding to acetylated HIV-1 integrase. Amino Acids. 2011;41:1137-45 pubmed publisher..Nevertheless, few two-hybrid hits bind with the same affinity the acetylated and the unmodified IN. These results further underlie the relevance of IN post-translational modification by acetylation in HIV-1 replication cycle. ..
- Hare S, Cherepanov P. The Interaction Between Lentiviral Integrase and LEDGF: Structural and Functional Insights. Viruses. 2009;1:780-801 pubmed publisher..This review focuses on the structural aspects of the IN-LEDGF interaction and their functional consequences. ..
- Llano M, Vanegas M, Hutchins N, Thompson D, Delgado S, Poeschla E. Identification and characterization of the chromatin-binding domains of the HIV-1 integrase interactor LEDGF/p75. J Mol Biol. 2006;360:760-73 pubmed..The results establish a molecular mechanism for LEDGF/p75-mediated tethering of HIV-1 integrase to chromatin. ..
- Raghavendra N, Engelman A. LEDGF/p75 interferes with the formation of synaptic nucleoprotein complexes that catalyze full-site HIV-1 DNA integration in vitro: implications for the mechanism of viral cDNA integration. Virology. 2007;360:1-5 pubmed..We therefore speculate that LEDGF/p75 function is restricted to a point in the viral lifecycle that occurs after the formation of the preintegration synaptic complex, for example, as a chromatin-associated tethering factor. ..
- Song C, Aiken C. Analysis of human cell heterokaryons demonstrates that target cell restriction of cyclosporine-resistant human immunodeficiency virus type 1 mutants is genetically dominant. J Virol. 2007;81:11946-56 pubmed..Collectively, these results support the existence of a cell-specific human cellular factor capable of restricting HIV-1 at an early post-entry step by a CypA-dependent mechanism. ..
- Hare S, Di Nunzio F, Labeja A, Wang J, Engelman A, Cherepanov P. Structural basis for functional tetramerization of lentiviral integrase. PLoS Pathog. 2009;5:e1000515 pubmed publisher..Our structures moreover highlight adaptable changes at the interfaces of individual IN dimers that allow divergent lentiviruses to utilize a highly-conserved, common integration co-factor...
- Gérard A, Soler N, Segeral E, Belshan M, Emiliani S. Identification of low molecular weight nuclear complexes containing integrase during the early stages of HIV-1 infection. Retrovirology. 2013;10:13 pubmed publisher..Our findings indicate that, shortly after viral entry, a significant portion of DNA-free IN that is distinct from active pre-integration complexes accumulates in the nucleus. ..
- Ventoso I, Navarro J, Muñoz M, Carrasco L. Involvement of HIV-1 protease in virus-induced cell killing. Antiviral Res. 2005;66:47-55 pubmed..These findings may contribute towards a better understanding of HIV-1 pathogenesis, and emphasise the potential of the virus protease as a key therapeutic target in AIDS treatment. ..
- Suzuki Y, Craigie R. The road to chromatin - nuclear entry of retroviruses. Nat Rev Microbiol. 2007;5:187-96 pubmed..Before integration into the host genome can occur, this complex must be transported to the nucleus and must cross the nuclear envelope. This Review summarizes our current knowledge of how this journey is accomplished. ..
- Mendieta J, Cases González C, Matamoros T, Ramirez G, Menendez Arias L. A Mg2+-induced conformational switch rendering a competent DNA polymerase catalytic complex. Proteins. 2008;71:565-74 pubmed..5 A. Our findings provide a detailed description of the mechanism of DNA polymerization and should be helpful to understand the molecular basis of DNA replication fidelity. ..
- Sayer J, Liu F, Ishima R, Weber I, Louis J. Effect of the active site D25N mutation on the structure, stability, and ligand binding of the mature HIV-1 protease. J Biol Chem. 2008;283:13459-70 pubmed publisher..DRV by a factor of approximately 10(6) relative to PR.DRV. These results suggest that interactions mediated by the catalytic Asp residues make a major contribution to the tight binding of DRV to PR. ..
- Vandekerckhove L, Christ F, Van Maele B, De Rijck J, Gijsbers R, Van den Haute C, et al. Transient and stable knockdown of the integrase cofactor LEDGF/p75 reveals its role in the replication cycle of human immunodeficiency virus. J Virol. 2006;80:1886-96 pubmed..Altogether, our data validate LEDGF/p75 as an important cellular cofactor for HIV integration and as a potential target for antiviral drug development. ..
- Ao Z, Huang G, Yao H, Xu Z, Labine M, Cochrane A, et al. Interaction of human immunodeficiency virus type 1 integrase with cellular nuclear import receptor importin 7 and its impact on viral replication. J Biol Chem. 2007;282:13456-67 pubmed..5-3.5-fold inhibition of HIV infection. Altogether, our results indicate that HIV-1 IN specifically interacts with Imp7, and this viral/cellular protein interaction contributes to efficient HIV-1 infection. ..
- Meehan A, Saenz D, Morrison J, Garcia Rivera J, Peretz M, Llano M, et al. LEDGF/p75 proteins with alternative chromatin tethers are functional HIV-1 cofactors. PLoS Pathog. 2009;5:e1000522 pubmed publisher..NDE mutants were corroborative. Chromatin tethering per se is a basic HIV-1 requirement and this rather than engagement of particular chromatin ligands is important for the LEDGF/p75 cofactor mechanism. ..
- Christ F, Debyser Z. The LEDGF/p75 integrase interaction, a novel target for anti-HIV therapy. Virology. 2013;435:102-9 pubmed publisher..In this review we will highlight the research validating the LEDGF/p75-IN interaction as a target for anti-HIV drug discovery and the recent advances in the design and development of LEDGINs. ..
- Chamanian M, Purzycka K, Wille P, Ha J, McDonald D, Gao Y, et al. A cis-acting element in retroviral genomic RNA links Gag-Pol ribosomal frameshifting to selective viral RNA encapsidation. Cell Host Microbe. 2013;13:181-92 pubmed publisher..Thus, only the HIV-1 RNAs employed for Gag-Pol translation may be specifically selected for encapsidation, possibly explaining the limitation of two gRNAs per virion. ..
- Jurado K, Wang H, Slaughter A, Feng L, Kessl J, Koh Y, et al. Allosteric integrase inhibitor potency is determined through the inhibition of HIV-1 particle maturation. Proc Natl Acad Sci U S A. 2013;110:8690-5 pubmed publisher..The vulnerability of IN to small molecules during the late phase of HIV-1 replication unveils a pharmacological Achilles' heel for exploitation in clinical ALLINI development...
- Topper M, Luo Y, Zhadina M, Mohammed K, Smith L, Muesing M. Posttranslational acetylation of the human immunodeficiency virus type 1 integrase carboxyl-terminal domain is dispensable for viral replication. J Virol. 2007;81:3012-7 pubmed..Although IN belongs to the very small set of nonhistone proteins modified by HAT-mediated activity, an obligate role for acetylation at the reactive CTD lysines in HIV-1 IN cannot be confirmed. ..
- Van Maele B, Debyser Z. HIV-1 integration: an interplay between HIV-1 integrase, cellular and viral proteins. AIDS Rev. 2005;7:26-43 pubmed..In this review we summarize the candidate cellular proteins involved in the HIV-1 integration process identified so far and discuss their potential roles during HIV-1 replication. ..
- Nie Z, Bren G, Vlahakis S, Schimnich A, Brenchley J, Trushin S, et al. Human immunodeficiency virus type 1 protease cleaves procaspase 8 in vivo. J Virol. 2007;81:6947-56 pubmed..These data indicate that casp8p41 independently induces apoptosis and is a specific product of HIV-1 protease which may contribute to death of HIV-1-infected cells. ..
- Hendrix J, Gijsbers R, De Rijck J, Voet A, Hotta J, McNeely M, et al. The transcriptional co-activator LEDGF/p75 displays a dynamic scan-and-lock mechanism for chromatin tethering. Nucleic Acids Res. 2011;39:1310-25 pubmed publisher..The PWWP is crucial for locking the complex on chromatin. We propose a scan-and-lock model for LEDGF/p75, unifying paradoxical notions of transcriptional co-activation and lentiviral integration targeting. ..
- Fregoso O, Ahn J, Wang C, Mehrens J, Skowronski J, Emerman M. Evolutionary toggling of Vpx/Vpr specificity results in divergent recognition of the restriction factor SAMHD1. PLoS Pathog. 2013;9:e1003496 pubmed publisher..Such drastic functional divergence within a lentiviral protein highlights a novel plasticity in the evolutionary dynamics of viral antagonists for restriction factors during lentiviral adaptation to its hosts. ..
- Dobard C, Briones M, Chow S. Molecular mechanisms by which human immunodeficiency virus type 1 integrase stimulates the early steps of reverse transcription. J Virol. 2007;81:10037-46 pubmed..Taken together, our results showed that IN acts at early steps of reverse transcription by increasing the processivity of RT and suppressing the formation of the pause products. ..
- Wang X, Ao Z, Chen L, Kobinger G, Peng J, Yao X. The cellular antiviral protein APOBEC3G interacts with HIV-1 reverse transcriptase and inhibits its function during viral replication. J Virol. 2012;86:3777-86 pubmed publisher..Overall, this paper provides evidence for the physical and functional interaction between A3G and HIV-1 RT and demonstrates that this interaction plays an important role in the action of A3G against HIV-1 reverse transcription. ..
- Ciuffi A, Llano M, Poeschla E, Hoffmann C, Leipzig J, Shinn P, et al. A role for LEDGF/p75 in targeting HIV DNA integration. Nat Med. 2005;11:1287-9 pubmed..LEDGF is thus the first example of a cellular protein controlling the location of HIV integration in human cells. ..
- Bartholomeeusen K, De Rijck J, Busschots K, Desender L, Gijsbers R, Emiliani S, et al. Differential interaction of HIV-1 integrase and JPO2 with the C terminus of LEDGF/p75. J Mol Biol. 2007;372:407-21 pubmed..Furthermore, JPO2 over-expression activated transcription from the HIV-1 LTR. ..
- Bartholomeeusen K, Christ F, Hendrix J, Rain J, Emiliani S, Benarous R, et al. Lens epithelium-derived growth factor/p75 interacts with the transposase-derived DDE domain of PogZ. J Biol Chem. 2009;284:11467-77 pubmed publisher..The finding that LEDGF/p75 is capable of interacting with a DDE domain protein that is not a lentiviral integrase points to a profound role of LEDGF/p75 in DDE domain protein function. ..
- Schuckmann M, Marchand B, Hachiya A, Kodama E, Kirby K, Singh K, et al. The N348I mutation at the connection subdomain of HIV-1 reverse transcriptase decreases binding to nevirapine. J Biol Chem. 2010;285:38700-9 pubmed publisher..In conclusion, connection subdomain mutation N348I decreases catalytic efficiency and causes in vitro resistance to NVP by decreasing inhibitor binding. ..
- Matreyek K, Engelman A. The requirement for nucleoporin NUP153 during human immunodeficiency virus type 1 infection is determined by the viral capsid. J Virol. 2011;85:7818-27 pubmed publisher..These results suggest that capsid, likely by the qualities of its uncoating, determines whether HIV-1 requires cellular NUP153 for PIC nuclear import. ..
- Fan X, Zhang F, Al Safi R, Zeng L, Shabaik Y, Debnath B, et al. Design of HIV-1 integrase inhibitors targeting the catalytic domain as well as its interaction with LEDGF/p75: a scaffold hopping approach using salicylate and catechol groups. Bioorg Med Chem. 2011;19:4935-52 pubmed publisher..This work provides a new and efficient approach to evolve novel HIV-1 IN inhibitors from rational integration and optimization of previously reported inhibitors. ..
- 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. ..
- Matreyek K, Engelman A. Viral and cellular requirements for the nuclear entry of retroviral preintegration nucleoprotein complexes. Viruses. 2013;5:2483-511 pubmed publisher..In this review, we describe our current understanding of retroviral nuclear import, with emphasis on recent developments on the role of the HIV-1 capsid protein. ..
- Luo K, Wang T, Liu B, Tian C, Xiao Z, Kappes J, et al. Cytidine deaminases APOBEC3G and APOBEC3F interact with human immunodeficiency virus type 1 integrase and inhibit proviral DNA formation. J Virol. 2007;81:7238-48 pubmed..Thus, multiple steps of the HIV-1 replication cycle, most noticeably the formation of proviral DNA, are inhibited by both cytidine deamination-dependent and -independent mechanisms. ..
- Hou Y, McGuinness D, Prongay A, Feld B, Ingravallo P, Ogert R, et al. Screening for antiviral inhibitors of the HIV integrase-LEDGF/p75 interaction using the AlphaScreen luminescent proximity assay. J Biomol Screen. 2008;13:406-14 pubmed publisher..This assay proved to be quite robust (with a Z' factor of 0.84 in screening libraries arrayed as orthogonal mixtures) and successfully identified several compounds specific for this protein-protein interaction. ..
- Rain J, Cribier A, Gérard A, Emiliani S, Benarous R. Yeast two-hybrid detection of integrase-host factor interactions. Methods. 2009;47:291-7 pubmed publisher..All tolled, our studies identified LEDGF/p75, Transportin-SR2 (TNPO3), von Hippel-Lindau binding protein 1 (VBP1), and sucrose non-fermenting 5 (SNF5) as cellular binding partners of HIV-1 integrase. ..
- Lee K, Ambrose Z, Martin T, Oztop I, Mulky A, Julias J, et al. Flexible use of nuclear import pathways by HIV-1. Cell Host Microbe. 2010;7:221-33 pubmed publisher..These findings reveal a remarkable flexibility in HIV-1 nuclear transport and highlight a single residue in CA as essential in regulating interactions with NUPs. ..
- De Luca L, Ferro S, Morreale F, De Grazia S, Chimirri A. Inhibitors of the interactions between HIV-1 IN and the cofactor LEDGF/p75. ChemMedChem. 2011;6:1184-91 pubmed publisher..We describe herein the progress to date in developing inhibitors of this promising target. ..
- Emiliani S, Mousnier A, Busschots K, Maroun M, Van Maele B, Tempé D, et al. Integrase mutants defective for interaction with LEDGF/p75 are impaired in chromosome tethering and HIV-1 replication. J Biol Chem. 2005;280:25517-23 pubmed..Furthermore, we found that LEDGF/p75 tethers HIV-1 integrase to chromosomes and that this interaction may be important for the integration process and the replication of HIV-1. ..
- Hombrouck A, De Rijck J, Hendrix J, Vandekerckhove L, Voet A, De Maeyer M, et al. Virus evolution reveals an exclusive role for LEDGF/p75 in chromosomal tethering of HIV. PLoS Pathog. 2007;3:e47 pubmed..Moreover, the role of LEDGF/p75 in targeting integration will stimulate research on strategies to direct gene therapy vectors into safe landing sites. ..
- Yap S, Sheen C, Fahey J, Zanin M, Tyssen D, Lima V, et al. N348I in the connection domain of HIV-1 reverse transcriptase confers zidovudine and nevirapine resistance. PLoS Med. 2007;4:e335 pubmed..This study also provides compelling evidence for investigating the role of other mutations in the connection and RNase H domains in virological failure. ..
- 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. ..
- Johnson B, Metifiot M, Ferris A, Pommier Y, Hughes S. A homology model of HIV-1 integrase and analysis of mutations designed to test the model. J Mol Biol. 2013;425:2133-46 pubmed publisher..Our model can be used to explain the phenotype of previously published HIV-1 IN mutants. We made additional mutants, and the behavior of these new mutants provides additional support for the model...
- Iwatani Y, Chan D, Wang F, Maynard K, Sugiura W, Gronenborn A, et al. Deaminase-independent inhibition of HIV-1 reverse transcription by APOBEC3G. Nucleic Acids Res. 2007;35:7096-108 pubmed..These data support a novel mechanism for deaminase-independent inhibition of reverse transcription that is determined by critical differences in the nucleic acid binding properties of A3G, NC and RT. ..
- Van Maele B, Busschots K, Vandekerckhove L, Christ F, Debyser Z. Cellular co-factors of HIV-1 integration. Trends Biochem Sci. 2006;31:98-105 pubmed..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. ..
- Ricci E, Soto Rifo R, Herbreteau C, Decimo D, Ohlmann T. Lentiviral RNAs can use different mechanisms for translation initiation. Biochem Soc Trans. 2008;36:690-3 pubmed publisher..Our results show that HIV-1 is able to drive the synthesis of the Gag polyprotein both by a classical cap-dependent mechanism and an IRES, whereas HIV-2 and SIV appear to use exclusively an IRES mechanism. ..
- De Luca L, Barreca M, Ferro S, Christ F, Iraci N, Gitto R, et al. Pharmacophore-based discovery of small-molecule inhibitors of protein-protein interactions between HIV-1 integrase and cellular cofactor LEDGF/p75. ChemMedChem. 2009;4:1311-6 pubmed publisher..This study is a valid starting point for the identification of anti-HIV agents with a different mechanism of action from currently available antiviral drugs. ..
- Inayoshi Y, Okino Y, Miyake K, Mizutani A, Yamamoto Kishikawa J, Kinoshita Y, et al. Transcription factor YY1 interacts with retroviral integrases and facilitates integration of moloney murine leukemia virus cDNA into the host chromosomes. J Virol. 2010;84:8250-61 pubmed publisher..Taking these results together, Yin Yang 1 appears to be involved in integration events during the early viral life cycle, possibly as an enhancer of integration...
- Yamamoto S, Okawa K, Nakano T, Sano K, Ogawa K, Masuda T, et al. Huwe1, a novel cellular interactor of Gag-Pol through integrase binding, negatively influences HIV-1 infectivity. Microbes Infect. 2011;13:339-49 pubmed publisher..Our results suggest that Huwe1 in HIV-1 producer cells has a negative impact on early post-entry events during the next round of virus infection via association with an IN region of Gag-Pol. ..
- Llano M, Saenz D, Meehan A, Wongthida P, Peretz M, Walker W, et al. An essential role for LEDGF/p75 in HIV integration. Science. 2006;314:461-4 pubmed..Perturbing the p75-integrase interaction may have therapeutic potential. ..
- Hayouka Z, Rosenbluh J, Levin A, Loya S, Lebendiker M, Veprintsev D, et al. Inhibiting HIV-1 integrase by shifting its oligomerization equilibrium. Proc Natl Acad Sci U S A. 2007;104:8316-21 pubmed..These peptides are promising anti-HIV lead compounds that modulate oligomerization of IN via a previously uncharacterized mechanism, which bears advantages over the conventional interface dimerization inhibitors. ..
- Dunn L, McWilliams M, Das K, Arnold E, Hughes S. Mutations in the thumb allow human immunodeficiency virus type 1 reverse transcriptase to be cleaved by protease in virions. J Virol. 2009;83:12336-44 pubmed publisher..The data suggest that the stability of a mutant RT in virions could be a major factor in determining the virus titer and, by extension, viral fitness, which could affect whether a mutation in RT is acceptable to the virus. ..
- Briones M, Dobard C, Chow S. Role of human immunodeficiency virus type 1 integrase in uncoating of the viral core. J Virol. 2010;84:5181-90 pubmed publisher..Taken together, our results indicate that IN is required during uncoating for maintaining CypA-CA interaction, which promotes optimal stability of the viral core. ..
- Shun M, Raghavendra N, Vandegraaff N, Daigle J, Hughes S, Kellam P, et al. LEDGF/p75 functions downstream from preintegration complex formation to effect gene-specific HIV-1 integration. Genes Dev. 2007;21:1767-78 pubmed..Akin to yeast retrotransposons, disrupting the lentiviral targeting mechanism significantly perturbs overall integration. ..
- Du L, Zhao Y, Chen J, Yang L, Zheng Y, Tang Y, et al. D77, one benzoic acid derivative, functions as a novel anti-HIV-1 inhibitor targeting the interaction between integrase and cellular LEDGF/p75. Biochem Biophys Res Commun. 2008;375:139-44 pubmed publisher..As the firstly discovered small molecular compound targeting HIV-1 integrase interaction with LEDGF/p75, D77 might supply useful structural information for further anti-HIV agent discovery. ..
- Hare S, Shun M, Gupta S, Valkov E, Engelman A, Cherepanov P. A novel co-crystal structure affords the design of gain-of-function lentiviral integrase mutants in the presence of modified PSIP1/LEDGF/p75. PLoS Pathog. 2009;5:e1000259 pubmed publisher..These findings provide structural basis for the high affinity lentiviral IN-LEDGF interaction and pave the way for development of LEDGF-based targeting technologies for gene therapy...
- Tsiang M, Jones G, Hung M, Mukund S, Han B, Liu X, et al. Affinities between the binding partners of the HIV-1 integrase dimer-lens epithelium-derived growth factor (IN dimer-LEDGF) complex. J Biol Chem. 2009;284:33580-99 pubmed publisher..This study revealed the significantly tighter nature of the IN-IN dimer compared with the IN-LEDGF interaction. ..
- Christ F, Voet A, Marchand A, Nicolet S, Desimmie B, Marchand D, et al. Rational design of small-molecule inhibitors of the LEDGF/p75-integrase interaction and HIV replication. Nat Chem Biol. 2010;6:442-8 pubmed publisher..Our work demonstrates the feasibility of rational design of small molecules inhibiting the protein-protein interaction between a viral protein and a cellular host factor. ..
- Varadarajan J, McWilliams M, Hughes S. Treatment with suboptimal doses of raltegravir leads to aberrant HIV-1 integrations. Proc Natl Acad Sci U S A. 2013;110:14747-52 pubmed publisher..The rearrangements of the host DNA raise concerns that these aberrant integrations might have unintended consequences in HIV-1-infected patients who are not consistent in following a raltegravir-containing treatment regimen. ..
- Vanegas M, Llano M, Delgado S, Thompson D, Peretz M, Poeschla E. Identification of the LEDGF/p75 HIV-1 integrase-interaction domain and NLS reveals NLS-independent chromatin tethering. J Cell Sci. 2005;118:1733-43 pubmed publisher..LEDGF/p75 is a multidomain adaptor protein that interacts with the nuclear import apparatus, lentiviral IN proteins and chromatin by means of an NLS, an IBD and additional chromatin-interacting domains...
- Rahman S, Lu R, Vandegraaff N, Cherepanov P, Engelman A. Structure-based mutagenesis of the integrase-LEDGF/p75 interface uncouples a strict correlation between in vitro protein binding and HIV-1 fitness. Virology. 2007;357:79-90 pubmed..Thus, the relative affinity of the in vitro IN-LEDGF/p75 interaction is not a universal predictor of IN mutant viral fitness. ..
- 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...
- Mousnier A, Kubat N, Massias Simon A, Segeral E, Rain J, Benarous R, et al. von Hippel Lindau binding protein 1-mediated degradation of integrase affects HIV-1 gene expression at a postintegration step. Proc Natl Acad Sci U S A. 2007;104:13615-20 pubmed..Results presented here support a role for integrase degradation by the prefoldin-VHL-proteasome pathway in the integration-transcription transition of the viral replication cycle. ..
- Botbol Y, Raghavendra N, Rahman S, Engelman A, Lavigne M. Chromatinized templates reveal the requirement for the LEDGF/p75 PWWP domain during HIV-1 integration in vitro. Nucleic Acids Res. 2008;36:1237-46 pubmed publisher..Our studies therefore establish novel in vitro conditions, highlighting chromatinized DNA as target acceptor templates, for physiologically relevant studies of LEDGF/p75 in lentiviral cDNA integration. ..
- Christ F, Thys W, De Rijck J, Gijsbers R, Albanese A, Arosio D, et al. Transportin-SR2 imports HIV into the nucleus. Curr Biol. 2008;18:1192-202 pubmed publisher..In comparison with control cell lines, the great majority of siRNA-treated cells did not contain any PIC in the nucleus. Our data clearly demonstrate that TRN-SR2 is the nuclear-import factor of HIV. ..
- Gao D, Wu J, Wu Y, Du F, Aroh C, Yan N, et al. Cyclic GMP-AMP synthase is an innate immune sensor of HIV and other retroviruses. Science. 2013;341:903-6 pubmed publisher..These results indicate that cGAS is an innate immune sensor of HIV and other retroviruses. ..
- Desfarges S, San Filippo J, Fournier M, Calmels C, Caumont Sarcos A, Litvak S, et al. Chromosomal integration of LTR-flanked DNA in yeast expressing HIV-1 integrase: down regulation by RAD51. Nucleic Acids Res. 2006;34:6215-24 pubmed..Our data allowed the identification of RAD51 as a novel in vitro IN cofactor able to down regulate the activity of this retroviral enzyme, thereby acting as a potential cellular restriction factor to HIV infection. ..
- Vandegraaff N, Engelman A. Molecular mechanisms of HIV integration and therapeutic intervention. Expert Rev Mol Med. 2007;9:1-19 pubmed..The progress towards developing integrase inhibitors for their use in the clinic is also reviewed. ..
- Poeschla E. Integrase, LEDGF/p75 and HIV replication. Cell Mol Life Sci. 2008;65:1403-24 pubmed publisher..Current goals are to establish the underlying mechanisms and to determine whether this knowledge can be exploited for antiviral therapy or for targeting lentiviral vector integration in human gene therapy. ..
- Lemay J, Maidou Peindara P, Cancio R, Ennifar E, Coadou G, Maga G, et al. AKAP149 binds to HIV-1 reverse transcriptase and is involved in the reverse transcription. J Mol Biol. 2008;383:783-96 pubmed publisher..This suggests that the interaction between RT and AKAP149 in infected cells may play an important role in HIV-1 reverse transcription. ..
- Das S, Kalpana G. Reverse two-hybrid screening to analyze protein-protein interaction of HIV-1 viral and cellular proteins. Methods Mol Biol. 2009;485:271-93 pubmed publisher..Once the mutants are isolated, they are tested in other biochemical systems and can be subjected to further functional and virological studies. ..