3'-end Processing and Kinetics of 5'-end Joining During Retroviral Integration in Vivo

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 1997 Feb 1

PMID 8995657

Citations 19

Authors

T Roe

S A Chow

P O Brown

Affiliations

Soon will be listed here.

Abstract

Retroviral replication depends on integration of viral DNA into a host cell chromosome. Integration proceeds in three steps: 3'-end processing, the endonucleolytic removal of the two terminal nucleotides from each 3' end of the viral DNA; strand transfer, the joining of the 3' ends of viral DNA to host DNA; and 5'-end joining (or gap repair), the joining of the 5' ends of viral DNA to host DNA. The 5'-end joining step has never been investigated, either for retroviral integration or for any other transposition process. We have developed an assay for 5'-end joining in vivo and have examined the kinetics of 5'-end joining for Moloney murine leukemia virus (MLV). The interval between 3'-end and 5'-end joining is estimated to be less than 1 h. This assay will be a useful tool for examining whether viral or host components mediate 5'-end joining. MLV integrates its DNA only after its host cell has completed mitosis. We show that the extent of 3'-end processing is the same in unsynchronized and aphidicolin-arrested cells. 3'-end processing therefore does not depend on mitosis.

Citing Articles

Viral Oncogenesis: Synergistic Role of Genome Integration and Persistence.

La Frazia S, Pauciullo S, Zulian V, Garbuglia A Viruses. 2025; 16(12.

PMID: 39772271 PMC: 11728759. DOI: 10.3390/v16121965.

Silencing of Unintegrated Retroviral DNAs.

Goff S Viruses. 2021; 13(11).

PMID: 34835055 PMC: 8621569. DOI: 10.3390/v13112248.

A CRISPR/Cas9 approach reveals that the polymerase activity of DNA polymerase β is dispensable for HIV-1 infection in dividing and nondividing cells.

Goetze R, Kim D, Schinazi R, Kim B J Biol Chem. 2017; 292(34):14016-14025.

PMID: 28684413 PMC: 5572920. DOI: 10.1074/jbc.M117.793661.

Retroviral intasomes search for a target DNA by 1D diffusion which rarely results in integration.

Jones N, Lopez Jr M, Hanne J, Peake M, Lee J, Fishel R Nat Commun. 2016; 7:11409.

PMID: 27108531 PMC: 4848512. DOI: 10.1038/ncomms11409.

Retroviral Integrase: Then and Now.

Andrake M, Skalka A Annu Rev Virol. 2016; 2(1):241-64.

PMID: 26958915 PMC: 4810031. DOI: 10.1146/annurev-virology-100114-055043.

References

Benjamin H, Kleckner N . Intramolecular transposition by Tn10. Cell. 1989; 59(2):373-83. DOI: 10.1016/0092-8674(89)90298-5. View

Walker G . Mutagenesis and inducible responses to deoxyribonucleic acid damage in Escherichia coli. Microbiol Rev. 1984; 48(1):60-93. PMC: 373003. DOI: 10.1128/mr.48.1.60-93.1984. View

Brown P . Integration of retroviral DNA. Curr Top Microbiol Immunol. 1990; 157:19-48. DOI: 10.1007/978-3-642-75218-6_2. View

Katzman M, KATZ R, Skalka A, Leis J . The avian retroviral integration protein cleaves the terminal sequences of linear viral DNA at the in vivo sites of integration. J Virol. 1989; 63(12):5319-27. PMC: 251198. DOI: 10.1128/JVI.63.12.5319-5327.1989. View

Bushman F, Fujiwara T, Craigie R . Retroviral DNA integration directed by HIV integration protein in vitro. Science. 1990; 249(4976):1555-8. DOI: 10.1126/science.2171144. View

Haniford D, Benjamin H, Kleckner N . Kinetic and structural analysis of a cleaved donor intermediate and a strand transfer intermediate in Tn10 transposition. Cell. 1991; 64(1):171-9. DOI: 10.1016/0092-8674(91)90218-n. View

HANAWALT P . Heterogeneity of DNA repair at the gene level. Mutat Res. 1991; 247(2):203-11. DOI: 10.1016/0027-5107(91)90016-h. View

Bainton R, Gamas P, Craig N . Tn7 transposition in vitro proceeds through an excised transposon intermediate generated by staggered breaks in DNA. Cell. 1991; 65(5):805-16. DOI: 10.1016/0092-8674(91)90388-f. View

Chow S, Vincent K, Ellison V, Brown P . Reversal of integration and DNA splicing mediated by integrase of human immunodeficiency virus. Science. 1992; 255(5045):723-6. DOI: 10.1126/science.1738845. View

10.

de Murcia G, Schreiber V . Poly(ADP-ribose) polymerase: molecular biological aspects. Bioessays. 1991; 13(9):455-62. DOI: 10.1002/bies.950130905. View

11.

Satoh M, Lindahl T . Role of poly(ADP-ribose) formation in DNA repair. Nature. 1992; 356(6367):356-8. DOI: 10.1038/356356a0. View

12.

Mizuuchi K . Transpositional recombination: mechanistic insights from studies of mu and other elements. Annu Rev Biochem. 1992; 61:1011-51. DOI: 10.1146/annurev.bi.61.070192.005051. View

13.

LaFemina R, Schneider C, Robbins H, Callahan P, LeGrow K, Roth E . Requirement of active human immunodeficiency virus type 1 integrase enzyme for productive infection of human T-lymphoid cells. J Virol. 1992; 66(12):7414-9. PMC: 240448. DOI: 10.1128/JVI.66.12.7414-7419.1992. View

14.

Sakai H, Kawamura M, Sakuragi J, Sakuragi S, Shibata R, Ishimoto A . Integration is essential for efficient gene expression of human immunodeficiency virus type 1. J Virol. 1993; 67(3):1169-74. PMC: 237481. DOI: 10.1128/JVI.67.3.1169-1174.1993. View

15.

Roe T, Reynolds T, Yu G, Brown P . Integration of murine leukemia virus DNA depends on mitosis. EMBO J. 1993; 12(5):2099-108. PMC: 413431. DOI: 10.1002/j.1460-2075.1993.tb05858.x. View

16.

Murphy J, de Los Santos T, Goff S . Mutational analysis of the sequences at the termini of the Moloney murine leukemia virus DNA required for integration. Virology. 1993; 195(2):432-40. DOI: 10.1006/viro.1993.1393. View

17.

Pahl A, Flugel R . Endonucleolytic cleavages and DNA-joining activities of the integration protein of human foamy virus. J Virol. 1993; 67(9):5426-34. PMC: 237944. DOI: 10.1128/JVI.67.9.5426-5434.1993. View

18.

Lavoie B, Chaconas G . Immunoelectron microscopic analysis of the A, B, and HU protein content of bacteriophage Mu transpososomes. J Biol Chem. 1990; 265(3):1623-7. View

19.

Ellison V, ABRAMS H, Roe T, Lifson J, Brown P . Human immunodeficiency virus integration in a cell-free system. J Virol. 1990; 64(6):2711-5. PMC: 249450. DOI: 10.1128/JVI.64.6.2711-2715.1990. View

20.

Eichinger D, Boeke J . A specific terminal structure is required for Ty1 transposition. Genes Dev. 1990; 4(3):324-30. DOI: 10.1101/gad.4.3.324. View