Quantitative analysis of the time-course of viral DNA forms during the HIV-1 life cycle

详细信息    查看全文

• 作者：Soundasse Munir (1)
  Sylvain Thierry (1)
  Frédéric Subra (1)
  Eric Deprez (1)
  Olivier Delelis (1)
  
• 关键词：HIV ; 1 ; 3-processing ; 1 ; LTR circles ; Integrase ; Strand transfer inhibitors
• 刊名：Retrovirology
• 出版年：2013
• 出版时间：December 2013
• 年：2013
• 卷：10
• 期：1
• 全文大小：812KB
• 参考文献：1. Sherman MP, Greene WC: Slipping through the door: HIV entry into the nucleus. / Microbes Infect 2002, 4:67-3. CrossRef
  2. Englund G, Theodore TS, Freed EO, Engelman A, Martin MA: Integration is required for productive infection of monocyte-derived macrophages by human-immunodeficiency-virus type-1. / J Virol 1995, 69:3216-219.
  3. Sakai H, Kawamura M, Sakuragi J, Sakuragi S, Shibata R, Ishimoto A, Ono N, Ueda S, Adachi A: Integration is essential for efficient gene expression of human immunodeficiency virus type 1. / J Virol 1993, 67:1169-174.
  4. Delelis O, Carayon K, Saib A, Deprez E, Mouscadet JF: Integrase and integration: biochemical activities of HIV-1 integrase. / Retrovirology 2008, 5:114. doi:10.1186/1742-4690-5-114. CrossRef
  5. Quashie PK, Mesplede T, Wainberg MA: Evolution of HIV integrase resistance mutations. / Curr Opin Infect Dis 2013, 26:43-9.
  6. Calmels C, De Soultrait VR, Caumont A, Desjobert C, Faure A, Fournier M, Tarrago-Litvak L, Parissi V: Biochemical and random mutagenesis analysis of the region carrying the catalytic E152 amino acid of HIV-1 integrase. / Nucleic Acids Res 2004, 32:1527-538. CrossRef
  7. Engelman A, Craigie R: Identification of conserved amino-acid-residues critical for human-immunodeficiency-virus type-1 integrase function-invitro. / J Virol 1992, 66:6361-369.
  8. Hazuda DJ, Felock P, Witmer M, Wolfe A, Stillmock K, Grobler JA, Espeseth A, Gabryelski L, Schleif W, Blau C, Miller MD: Inhibitors of strand transfer that prevent integration and inhibit HIV-1 replication in cells. / Science 2000, 287:646-50. CrossRef
  9. Fricke T, Valle-Casuso JC, White TE, Brandariz-Nunez A, Bosche WJ, Reszka N, Gorelick R, Diaz-Griffero F: The ability of TNPO3-depleted cells to inhibit HIV-1 infection requires CPSF6. / Retrovirology 2013, 10:46. CrossRef
  10. Tsiang M, Jones GS, Niedziela-Majka A, Kan E, Lansdon EB, Huang W, Hung M, Samuel D, Novikov N, Xu Y, / et al.: New class of HIV-1 integrase (IN) inhibitors with a dual mode of action. / J Biol Chem 2012, 287:21189-1203. CrossRef
  11. De Iaco A, Santoni F, Vannier A, Guipponi M, Antonarakis S, Luban J: TNPO3 protects HIV-1 replication from CPSF6-mediated capsid stabilization in the host cell cytoplasm. / Retrovirology 2013, 10:20. CrossRef
  12. Kilzer JM, Stracker T, Beitzel B, Meek K, Weitzman M, Bushman FD: Roles of host cell factors in circularization of retroviral DNA. / Virology 2003, 314:460-67. CrossRef
  13. Sloan RD, Wainberg MA: The role of unintegrated DNA in HIV infection. / Retrovirology 2011, 8:52. CrossRef
  14. Kim SY, Byrn R, Groopman J, Baltimore D: Temporal aspects of DNA and RNA synthesis during human immunodeficiency virus infection: evidence for differential gene expression. / J Virol 1989, 63:3708-713.
  15. Yan N, Cherepanov P, Daigle JE, Engelman A, Lieberman J: The SET complex acts as a barrier to autointegration of HIV. / Plos Pathog 2009, 1:5.
  16. Sloan RD, Kuhl BD, Donahue DA, Roland A, Bar-Magen T, Wainberg MA: Transcription of preintegrated HIV-1 cDNA modulates cell surface expression of major histocompatibility complex class I via Nef. / J Virol 2011, 85:2828-836. CrossRef
  17. Zennou V, Petit C, Guetard D, Nerhbass U, Montagnier L, Charneau P: HIV-1 genome nuclear import is mediated by a central DNA flap. / Cell 2000, 101:173-85. CrossRef
  18. Brussel A, Sonigo P: Analysis of early human immunodeficiency virus type 1 DNA synthesis by use of a new sensitive assay for quantifying integrated provirus. / J Virol 2003, 77:10119-0124. CrossRef
  19. Butler SL, Hansen MST, Bushman FD: A quantitative assay for HIV DNA integration in vivo. / Nat Med 2001, 7:631-34. CrossRef
  20. Yoder KE, Fishel R: PCR-based detection is unable to consistently distinguish HIV 1LTR circles. / J Virol Methods 2006, 138:201-06. CrossRef
  21. Mohammed KD, Topper MB, Muesing MA: Sequential deletion of the integrase (Gag-Pol) carboxyl terminus reveals distinct phenotypic classes of defective HIV-1. / J Virol 2011, 85:4654-666. CrossRef
  22. Pierson TC, Zhou Y, Kieffer TL, Ruff CT, Buck C, Siliciano RF: Molecular characterization of preintegration latency in human immunodeficiency virus type 1 infection. / J Virol 2002, 76:8518-531. CrossRef
  23. Iglesias C, Ringeard M, Di Nunzio F, Fernandez J, Gaudin R, Souque P, Charneau P, Arhel N: Residual HIV-1 DNA Flap-independent nuclear import of cPPT/CTS double mutant viruses does not support spreading infection. / Retrovirology 2011, 8:92. CrossRef
  24. Bukrinsky MI, Sharova N, Dempsey MP, Stanwick TL, Bukrinskaya AG, Haggerty S, Stevenson M: Active nuclear import of human immunodeficiency virus type 1 preintegration complexes. / Proc Natl Acad Sci U S A 1992, 89:6580-584. CrossRef
  25. Jacque JM, Stevenson M: The inner-nuclear-envelope protein emerin regulates HIV-1 infectivity. / Nature 2006, 441:641-45. CrossRef
  26. Gelderblom HC, Vatakis DN, Burke SA, Lawrie SD, Bristol GC, Levy DN: Viral complementation allows HIV-1 replication without integration. / Retrovirology 2008, 5:60. doi:10.1186/1742-4690-5-60. CrossRef
  27. Iyer SR, Yu D, Biancotto A, Margolis LB, Wu Y: Measurement of human immunodeficiency virus type 1 preintegration transcription by using Rev-dependent Rev-CEM cells reveals a sizable transcribing DNA population comparable to that from proviral templates. / J Virol 2009, 83:8662-673. CrossRef
  28. Li L, Olvera JM, Yoder KE, Mitchell RS, Butler SL, Lieber M, Martin SL, Bushman FD: Role of the non-homologous DNA end joining pathway in the early steps of retroviral infection. / Embo J 2001, 20:3272-281. CrossRef
  29. Delelis O, Malet I, Na L, Tchertanov L, Calvez V, Marcelin AG, Subra F, Deprez E, Mouscadet JF: The G140S mutation in HIV integrases from raltegravir-resistant patients rescues catalytic defect due to the resistance Q148H mutation. / Nucleic Acids Res 2009, 37:1193-201. CrossRef
  30. Miller MD, Wang B, Bushman FD: Human immunodeficiency virus type 1 preintegration complexes containing discontinuous plus strands are competent to integrate in vitro. / J Virol 1995, 69:3938-944.
  31. Bukrinsky MI, Stanwick TL, Dempsey MP, Stevenson M: Quiescent lymphocytes-T as an inducible virus reservoir in Hiv-1 infection. / Science 1991, 254:423-27. CrossRef
  32. Levin A, Armon-Omer A, Rosenbluh J, Melamed-Book N, Graessmann A, Waigmann E, Loyter A: Inhibition of HIV-1 integrase nuclear import and replication by a peptide bearing integrase putative nuclear localization signal. / Retrovirology 2009, 6:112. doi:10.1186/1742-4690-6-112. CrossRef
  33. Arhel N, Munier S, Souque P, Mollier K, Charneau P: Nuclear import defect of human immunodeficiency virus type 1 DNA flap mutants is not dependent on the viral strain or target cell type. / J Virol 2006, 80:10262-0269. CrossRef
  34. Dvorin JD, Bell P, Maul GG, Yamashita M, Emerman M, Malim MH: Reassessment of the roles of integrase and the central DNA flap in human immunodeficiency virus type 1 nuclear import. / J Virol 2002, 76:12087-2096. CrossRef
  35. Limon A, Nakajima N, Lu R, Ghory HZ, Engelman A: Wild-type levels of nuclear localization and human immunodeficiency virus type 1 replication in the absence of the central DNA flap. / J Virol 2002, 76:12078-2086. CrossRef
  36. Marsden MD, Zack JA: Human immunodeficiency virus bearing a disrupted central DNA flap is pathogenic in vivo. / J Virol 2007, 81:6146-150. CrossRef
  37. Marinello J, Marchand C, Mott BT, Bain A, Thomas CJ, Pommier Y: Comparison of raltegravir and elvitegravir on HIV-1 integrase catalytic reactions and on a series of drug-resistant integrase mutants. / Biochemistry-Us 2008, 47:9345-354. CrossRef
  38. Chen HM, Engelman A: Asymmetric processing of human immunodeficiency virus type 1 cDNA in vivo: implications for functional end coupling during the chemical steps of DNA transposition. / Mol Cell Biol 2001, 21:6758-767. CrossRef
  39. Nguyen BY, Isaacs RD, Teppler H, Leavitt RY, Sklar P, Iwamoto M, Wenning LA, Miller MD, Chen J, Kemp R, / et al.: Raltegravir: the first HIV-1 integrase strand transfer inhibitor in the HIV armamentarium. / Ann N Y Acad Sci 2011, 1222:83-9. CrossRef
  40. Miller MD, Farnet CM, Bushman FD: Human immunodeficiency virus type 1 preintegration complexes: Studies of organization and composition. / J Virol 1997, 71:5382-390.
  41. Katlama C, Murphy R: Dolutegravir for the treatment of HIV. / Expert Opin Investig Drugs 2012, 21:523-30. CrossRef
  42. Marchand C: The elvitegravir Quad pill: the first once-daily dual-target anti-HIV tablet. / Expert Opin Investig Drugs 2012, 21:901-04. CrossRef
  43. Metifiot M, Maddali K, Naumova A, Zhang X, Marchand C, Pommier Y: Biochemical and pharmacological analyses of HIV-1 integrase flexible loop mutants resistant to raltegravir. / Biochemistry-Us 2010, 49:3715-722. CrossRef
  44. Yoder K, Sarasin A, Kraemer K, McIlhatton M, Bushman F, Fishel R: The DNA repair genes XPB and XPD defend cells from retroviral infection. / Proc Natl Acad Sci U S A 2006, 103:4622-627. CrossRef
  45. Fischer M, Trkola A, Joos B, Hafner R, Joller H, Muesing MA, Kaufman DR, Berli E, Hirschel B, Weber R, Gunthard HF: Shifts in cell-associated HIV-1 RNA but not in episomal HIV-1 DNA correlate with new cycles of HIV-1 infection in vivo. / Antivir Ther 2003, 8:97-04.
  46. Wu YT, Marsh JW: Early transcription from nonintegrated DNA in human immunodeficiency virus infection. / J Virol 2003, 77:10376-0382. CrossRef
  47. Bar-Magen T, Sloan RD, Faltenbacher VH, Donahue DA, Kuhl BD, Oliveira M, Xu HT, Wainberg MA: Comparative biochemical analysis of HIV-1 subtype B and C integrase enzymes. / Retrovirology 2009, 6:103. doi:10.1186/1742-4690-6-103. CrossRef
  48. Underwood MR, Johns BA, Sato A, Martin JN, Deeks SG, Fujiwara T: The activity of the integrase inhibitor dolutegravir against HIV-1 variants isolated from raltegravir-treated adults. / J Acquir Immune Defic Syndr 2012, 61:297-01. CrossRef
  49. Shoemaker C, Goff S, Gilboa E, Paskind M, Mitra SW, Baltimore D: Structure of a cloned circular Moloney murine leukemia virus DNA molecule containing an inverted segment: implications for retrovirus integration. / Proc Natl Acad Sci USA 1980, 77:3932-936. CrossRef
  50. Emiliani S, Mousnier A, Busschots K, Maroun M, Van Maele B, Tempe D, Vandekerckhove L, Moisant F, Ben-Slama L, Witvrouw M, / et al.: Integrase mutants defective for interaction with LEDGF/p75 are impaired in chromosome tethering and HIV-1 replication. / J Biol Chem 2005, 280:25517-5523. CrossRef
  51. Petit C, Mathez D, Barthelemy C, Leste-Lasserre T, Naviaux RK, Sonigo P, Leibowitch J: Quantitation of blood lymphocyte mitochondrial DNA for the monitoring of antiretroviral drug-induced mitochondrial DNA depletion. / J Acquir Immune Defic Syndr 2003, 33:461-69. CrossRef
  52. Delelis O, Parissi V, Leh H, Mbemba G, Petit C, Sonigo P, Deprez E, Mouscadet JF: Efficient and specific internal cleavage of a retroviral palindromic DNA sequence by tetrameric HIV-1 integrase. / Plos One 2007, 2:e608. CrossRef
  
• 作者单位：Soundasse Munir (1)
  Sylvain Thierry (1)
  Frédéric Subra (1)
  Eric Deprez (1)
  Olivier Delelis (1)
  
  1. LBPA, ENS Cachan, CNRS, Cachan, France
  
• ISSN：1742-4690

文摘

Background HIV-1 DNA is found both integrated in the host chromosome and unintegrated in various forms: linear (DNAL) or circular (1-LTRc, 2-LTRc or products of auto-integration). Here, based on pre-established strategies, we extended and characterized in terms of sensitivity two methodologies for quantifying 1-LTRc and DNAL, respectively, the latter being able to discriminate between unprocessed or 3-processed DNA. Results Quantifying different types of viral DNA genome individually provides new information about the dynamics of all viral DNA forms and their interplay. For DNAL, we found that the 3-processing reaction was efficient during the early stage of the replication cycle. Moreover, strand-transfer inhibitors (Dolutegravir, Elvitegravir, Raltegravir) affected 3-processing differently. The comparisons of 2-LTRc accumulation mediated by either strand-transfer inhibitors or catalytic mutation of integrase indicate that 3-processing efficiency did not influence the total 2-LTRc accumulation although the nature of the LTR-LTR junction was qualitatively affected. Finally, a significant proportion of 1-LTRc was generated concomitantly with reverse transcription, although most of the 1-LTRc were produced in the nucleus. Conclusions We describe the fate of viral DNA forms during HIV-1 infection. Our study reveals the interplay between various forms of the viral DNA genome, the distribution of which can be affected by mutations and by inhibitors of HIV-1 viral proteins. 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.