Endonucleolytic cleavages and DNA-joining activities of the integration protein of human foamy virus

Pahl, Armin; Flügel, Rolf M.

doi:10.1128/jvi.67.9.5426-5434.1993

Cited by 47 publications

(29 citation statements)

References 38 publications

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“…The observed low-level processing of Gag precursors in the different cellular compartments of HFV-infected cells as well as in free viral particles is a characteristic feature of HFV. Several recent reports which focus on the Pol proteins of HFV and on viral protease activity tend to indicate a normal processing of the Pol precursor by viral protease leading to active DNA polymerase, RNase H, and integrase viral proteins (15,16,26,28). In this study, we produced the first evidence for a complete processing of Gag precursors by the HFV protease.…”

Section: Fig 2 Subcellular Localization and Maturation Of Incoming mentioning

confidence: 61%

Expression and maturation of human foamy virus Gag precursor polypeptides

Giron

Colas

Wybier

et al. 1997

J Virol

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In this report, we address the processing of the Gag polypeptides of human foamy virus previously reported to be atypical. In the cytoplasm or the nucleus of infected cells as well as in free virus particles, two Gag precursor polypeptides were identified at approximately 72 and 68 kDa, p72 giving rise to p68 by a maturation process. Efficient maturation of Gag precursors was observed only in two situations: (i) during the early steps of virus adsorption and (ii) under experimental conditions, including treatment with DNase I, known to dissociate actin polymers associated with high ionic strength and ionic detergents. Rather than being a defective viral protease function, an association of Gag precursors with a cytoskeleton network might be responsible for the low rate of Gag protein maturation through inhibition of their cleavage by the protease.

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Section: Fig 2 Subcellular Localization and Maturation Of Incoming mentioning

confidence: 61%

Expression and maturation of human foamy virus Gag precursor polypeptides

Giron

Colas

Wybier

et al. 1997

J Virol

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“…In addition, the effects of other base substitutions (1,16,18,22,26,29,31,33), abasic sites (22,29), mismatched base pairs (22,29,33), methylphosphonodiester substitution (21), and adduct interference (2) have been used to explore potentially important interactions between HIV-1 IN and viral U5 (2,16,18,21,22,26,29,31,33) or U3 (1,2,25) sequences during processing and DNA joining. Other INs have also been studied with altered substrates (6,10,13,23,24,28,30). However, general rules describing which viral DNA bases interact most critically with different integrases have not been defined.…”

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confidence: 99%

Influence of subterminal viral DNA nucleotides on differential susceptibility to cleavage by human immunodeficiency virus type 1 and visna virus integrases

Katzman

Sudol

1996

J Virol

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A comparison of the extents of site-specific cleavage of U5 and U3 viral DNA termini by the integrases of human immunodeficiency virus type 1 and visna virus guided the quantitative testing of oligonucleotide substrates containing specific base substitutions. The simultaneous exchange of positions 5 and 6 between U3 substrates switched the patterns of differential susceptibility to the two integrases. The activity of visna virus integrase was more dependent on the identity of position 5 adjacent to the invariant CA bases than on position 6, whereas human immunodeficiency virus type 1 integrase appeared to interact even more critically with position 6. Although the paired natural substrates of most lentiviral integrases match at positions 7 and 8, these bases were not important for susceptibility of U5 substrates. In fact, the final six U5 positions contained all of the sequence information necessary for susceptibility. These results suggest that constraints other than integration influence the terminal inverted repeats of retroviral DNA.

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“…Purified recombinant integrase proteins display 3′ processing and strand transfer activities in vitro (22)(23)(24)(25)(26)(27)(28)(29)(30). Simplified assay systems utilized relatively short (~17-22 bp) double-stranded oligonucleotides that model the ends of the LTRs for 3′ processing reaction substrates (22,24) and also for acceptor target DNA during strand transfer (23,26,27,29,30). Because pre-processed substrates that lacked sequences normally removed during 3′ processing supported strand transfer activity, the integration of retroviral DNA ends is mechanistically separable from dinucleotide cleavage (23,26,27,29,30).…”

Section: Integrase Activitiesmentioning

confidence: 99%

“…Simplified assay systems utilized relatively short (~17-22 bp) double-stranded oligonucleotides that model the ends of the LTRs for 3′ processing reaction substrates (22,24) and also for acceptor target DNA during strand transfer (23,26,27,29,30). Because pre-processed substrates that lacked sequences normally removed during 3′ processing supported strand transfer activity, the integration of retroviral DNA ends is mechanistically separable from dinucleotide cleavage (23,26,27,29,30). Concordantly, 3′ processing of HIV-1 DNA ends can occur soon after the LTRs are synthesized (31,32), which precedes integration into chromosomal DNA minimally by several hours (33,34).…”

Section: Integrase Activitiesmentioning

confidence: 99%

Retroviral Integrase Structure and DNA Recombination Mechanism

Engelman

Cherepanov

2015

Mobile DNA III

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Due to the importance of human immunodeficiency virus type 1 (HIV-1) integrase as a drug target, the biochemistry and structural aspects of retroviral DNA integration have been the focus of intensive research during the past three decades. The retroviral integrase enzyme acts on the linear double-stranded viral DNA product of reverse transcription. Integrase cleaves specific phosphodiester bonds near the viral DNA ends during the 3′ processing reaction. The enzyme then uses the resulting viral DNA 3′-OH groups during strand transfer to cut chromosomal target DNA, which simultaneously joins both viral DNA ends to target DNA 5′-phosphates. Both reactions proceed via direct transesterification of scissile phosphodiester bonds by attacking nucleophiles: a water molecule for 3′ processing, and the viral DNA 3′-OH for strand transfer. X-ray crystal structures of prototype foamy virus integrase-DNA complexes revealed the architectures of the key nucleoprotein complexes that form sequentially during the integration process and explained the roles of active site metal ions in catalysis. X-ray crystallography furthermore elucidated the mechanism of action of HIV-1 integrase strand transfer inhibitors, which are currently used to treat AIDS patients, and provided valuable insights into the mechanisms of viral drug resistance.Retroviridae is composed of two virus subfamilies, Orthoretrovirinae and Spumaretrovirinae. While six viral genera, including alpha through epsilon and lenti, belong to Orthoretrovirinae, the spumaviruses solely comprise Spumaretrovirinae. Spumavirus NIH Public Access

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Endonucleolytic cleavages and DNA-joining activities of the integration protein of human foamy virus

Cited by 47 publications

References 38 publications

Expression and maturation of human foamy virus Gag precursor polypeptides

Expression and maturation of human foamy virus Gag precursor polypeptides

Influence of subterminal viral DNA nucleotides on differential susceptibility to cleavage by human immunodeficiency virus type 1 and visna virus integrases

Retroviral Integrase Structure and DNA Recombination Mechanism

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