The HIV-1 replication cycle is composed of several sequential steps. While the timing of the early steps of HIV-1 replication is quite well understood, measuring the duration of later steps is complicated by the fact that asynchrony is introduced into populations of infected cells during early steps. We devised imaging methods for measuring the duration of late steps in HIV-1 replication in single infected cells, circumventing the problems associated with measurements in populations of asynchronously infected cells. By combining these measurements with conventional analyses of HIV-1 replication in populations of cells, we derived a time-line of key events during the late steps of the HIV-1 life cycle. We find that the delay between early and late gene expression is small but that a subsequent programmed delay in virus assembly enables HIV-1 to remove a host antiviral protein from infected cells before new virions are generated. In so doing, HIV-1 may prevent futile virion production.
Vyšlo v časopise: Single-Cell and Single-Cycle Analysis of HIV-1 Replication. PLoS Pathog 11(6): e32767. doi:10.1371/journal.ppat.1004961 Kategorie: Research Article prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004961
1. Fernandez-Larsson R, Srivastava KK, Lu S, Robinson HL. Replication of patient isolates of human immunodeficiency virus type 1 in T cells: a spectrum of rates and efficiencies of entry. Proc Natl Acad Sci U S A. 1992;89(6):2223–6. 1549586
2. Srivastava KK, Fernandez-Larsson R, Zinkus DM, Robinson HL. Human immunodeficiency virus type 1 NL4-3 replication in four T-cell lines: rate and efficiency of entry, a major determinant of permissiveness. J. Virol. 1991;65(7):3900–2. 1674969
3. Platt EJ, Durnin JP, Kabat D. Kinetic factors control efficiencies of cell entry, efficacies of entry inhibitors, and mechanisms of adaptation of human immunodeficiency virus. J. Virol. 2005;79(7):4347–56. 15767435
4. Reeves JD, Gallo SA, Ahmad N, Miamidian JL, Harvey PE, Sharron M, et al. Sensitivity of HIV-1 to entry inhibitors correlates with envelope/coreceptor affinity, receptor density, and fusion kinetics. Proc Natl Acad Sci U S A. 2002;99(25):16249–54. 12444251
5. Perez-Caballero D, Hatziioannou T, Zhang F, Cowan S, Bieniasz PD. Restriction of Human Immunodeficiency Virus Type 1 by TRIM-CypA Occurs with Rapid Kinetics and Independently of Cytoplasmic Bodies, Ubiquitin, and Proteasome Activity. J. Virol. 2005;79(24):15567–72. 16306627
6. Donahue DA, Sloan RD, Kuhl BD, Bar-Magen T, Schader SM, Wainberg MA. Stage-dependent inhibition of HIV-1 replication by antiretroviral drugs in cell culture. Antimicrob Agents Chemother. 2010;54(3):1047–54. doi: 10.1128/AAC.01537-09 20038621
7. Murray JM, Kelleher AD, Cooper DA. Timing of the Components of the HIV Life Cycle in Productively Infected CD4+ T Cells in a Population of HIV-Infected Individuals. J Virol. 2011;85(20):10798–805. doi: 10.1128/JVI.05095-11 21835801
8. Collin M, Gordon S. The Kinetics of Human Immunodeficiency Virus Reverse Transcription Are Slower in Primary Human Macrophages Than in a Lymphoid Cell Line. Virology. 1994;200(1):114–20. 7510432
9. O'Brien WA, Namazi A, Kalhor H, Mao SH, Zack JA, Chen IS. Kinetics of human immunodeficiency virus type 1 reverse transcription in blood mononuclear phagocytes are slowed by limitations of nucleotide precursors. J. Virol. 1994;68(2):1258–63. 7507180
10. Kim B, Nguyen LA, Daddacha W, Hollenbaugh JA. Tight Interplay Among SAMHD1 Level, Cellular dNTP Levels and HIV-1 Proviral DNA Synthesis Kinetics in Human Primary Monocyte-Derived Macrophages. J Biol Chem. 2012.
11. Tomaras GD, Lacey SF, McDanal CB, Ferrari G, Weinhold KJ, Greenberg ML. CD8+ T cell-mediated suppressive activity inhibits HIV-1 after virus entry with kinetics indicating effects on virus gene expression. Proc Natl Acad Sci U S A. 2000;97(7):3503–8. 10725407
12. Lalonde MS, Lobritz MA, Ratcliff A, Chamanian M, Athanassiou Z, Tyagi M, et al. Inhibition of both HIV-1 reverse transcription and gene expression by a cyclic peptide that binds the Tat-transactivating response element (TAR) RNA. PLoS Pathogens. 2011;7(5):e1002038. doi: 10.1371/journal.ppat.1002038 21625572
13. Dixit NM, Markowitz M, Ho DD, Perelson AS. Estimates of intracellular delay and average drug efficacy from viral load data of HIV-infected individuals under antiretroviral therapy. Antiviral therapy. 2004;9(2):237–46. 15134186
14. Markowitz M, Louie M, Hurley A, Sun E, Di Mascio M, Perelson AS, et al. A novel antiviral intervention results in more accurate assessment of human immunodeficiency virus type 1 replication dynamics and T-cell decay in vivo. J Virol. 2003;77(8):5037–8. 12663814
15. Mohri H, Perelson AS, Tung K, Ribeiro RM, Ramratnam B, Markowitz M, et al. Increased turnover of T lymphocytes in HIV-1 infection and its reduction by antiretroviral therapy. J Exp Med. 2001;194(9):1277–87. 11696593
16. Mittler JE, Markowitz M, Ho DD, Perelson AS. Improved estimates for HIV-1 clearance rate and intracellular delay. AIDS. 1999;13(11):1415–7. 10449298
17. Perelson AS, Neumann AU, Markowitz M, Leonard JM, Ho DD. HIV-1 dynamics in vivo: virion clearance rate, infected cell life-span, and viral generation time. Science. 1996;271(5255):1582–6. 8599114
18. Ho DD, Neumann AU, Perelson AS, Chen W, Leonard JM, Markowitz M. Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature. 1995;373(6510):123–6. 7816094
19. Coombs D. Optimal viral production. Bull Math Biol. 2003;65(6):1003–23. 14607286
20. Purcell DF, Martin MA. Alternative splicing of human immunodeficiency virus type 1 mRNA modulates viral protein expression, replication, and infectivity. J Virol. 1993;67(11):6365–78. 8411338
21. Malim MH, Hauber J, Le S-Y, Maizel JV, Cullen BR. The HIV-1 rev trans-activator acts through a structured target sequence to activate nuclear export of unspliced viral mRNA. Nature. 1989;338(6212):254–7. 2784194
22. Zapp ML, Green MR. Sequence-specific RNA binding by the HIV-1 Rev protein. Nature. 1989;342(6250):714–6. 2556643
23. Malim MH, McCarn DF, Tiley LS, Cullen BR. Mutational definition of the human immunodeficiency virus type 1 Rev activation domain. J Virol. 1991;65(8):4248–54. 2072452
24. Malim MH, Böhnlein S, Hauber J, Cullen BR. Functional dissection of the HIV-1 Rev trans-activator—derivation of a trans-dominant repressor of Rev function. Cell. 1989;58(1):205–14. 2752419
25. 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(9):3708–13. 2760980
26. Fornerod M, Ohno M, Yoshida M, Mattaj IW. CRM1 is an export receptor for leucine-rich nuclear export signals. Cell. 1997;90(6):1051–60. 9323133
27. Bogerd HP, Echarri A, Ross TM, Cullen BR. Inhibition of human immunodeficiency virus Rev and human T-cell leukemia virus Rex function, but not Mason-Pfizer monkey virus constitutive transport element activity, by a mutant human nucleoporin targeted to Crm1. J Virol. 1998;72(11):8627–35. 9765402
28. Fukuda M, Asano S, Nakamura T, Adachi M, Yoshida M, Yanagida M, et al. CRM1 is responsible for intracellular transport mediated by the nuclear export signal. Nature. 1997;390(6657):308–11. 9384386
29. Neville M, Stutz F, Lee L, Davis LI, Rosbash M. The importin-beta family member Crm1p bridges the interaction between Rev and the nuclear pore complex during nuclear export. Curr Biol. 1997;7(10):767–75. 9368759
30. Klotman ME, Kim S, Buchbinder A, DeRossi A, Baltimore D, Wong-Staal F. Kinetics of expression of multiply spliced RNA in early human immunodeficiency virus type 1 infection of lymphocytes and monocytes. Proc Natl Acad Sci USA. 1991;88(11):5011–5. 1711215
31. Gottlinger HG, Sodroski JG, Haseltine WA. Role of capsid precursor processing and myristoylation in morphogenesis and infectivity of human immunodeficiency virus type 1. Proc Natl Acad Sci U S A. 1989;86(15):5781–5. 2788277
32. Bryant M, Ratner L. Myristoylation-dependent replication and assembly of human immunodeficiency virus 1. Proc Natl Acad Sci USA. 1990;87(2):523–7. 2405382
33. Kutluay SB, Zang T, Blanco-Melo D, Powell C, Jannain D, Errando M, et al. Global Changes in the RNA Binding Specificity of HIV-1 Gag Regulate Virion Genesis. Cell. 2014;159(5):1096–109. doi: 10.1016/j.cell.2014.09.057 25416948
34. Chukkapalli V, Oh SJ, Ono A. Opposing mechanisms involving RNA and lipids regulate HIV-1 Gag membrane binding through the highly basic region of the matrix domain. Proc Natl Acad Sci USA. 2010;107(4):1600–5. doi: 10.1073/pnas.0908661107 20080620
35. Zhou W, Resh MD. Differential membrane binding of the human immunodeficiency virus type 1 matrix protein. J. Virol. 1996;70(12):8540–8. 8970978
36. Tang C, Loeliger E, Luncsford P, Kinde I, Beckett D, Summers MF. Entropic switch regulates myristate exposure in the HIV-1 matrix protein. Proc Natl Acad Sci U S A. 2004;101(2):517–22. 14699046
37. Saad JS, Miller J, Tai J, Kim A, Ghanam RH, Summers MF. Structural basis for targeting HIV-1 Gag proteins to the plasma membrane for virus assembly. Proc Natl Acad Sci USA. 2006;103(30):11364–9. 16840558
38. Spearman P, Horton R, Ratner L, Kuli-Zade I. Membrane binding of human immunodeficiency virus type 1 matrix protein in vivo supports a conformational myristyl switch mechanism. J Virol. 1997;71(9):6582–92. 9261380
39. Paillart JC, Göttlinger HG. Opposing effects of human immunodeficiency virus type 1 matrix mutations support a myristyl switch model of gag membrane targeting. J Virol. 1999;73(4):2604–12. 10074105
40. Reil H, Bukovsky AA, Gelderblom HR, Göttlinger HG. Efficient HIV-1 replication can occur in the absence of the viral matrix protein. EMBO J. 1998;17(9):2699–708. 9564051
41. Hatziioannou T, Martin-Serrano J, Zang T, Bieniasz PD. Matrix-Induced Inhibition of Membrane Binding Contributes to Human Immunodeficiency Virus Type 1 Particle Assembly Defects in Murine Cells. J Virol. 2005;79(24):15586–9. 16306631
42. Perez-Caballero D, Hatziioannou T, Martin-Serrano J, Bieniasz PD. Human Immunodeficiency Virus Type 1 Matrix Inhibits and Confers Cooperativity on Gag Precursor-Membrane Interactions. J Virol. 2004;78(17):9560–3. 15308748
43. Blanco-Melo D, Venkatesh S, Bieniasz PD. Intrinsic cellular defenses against human immunodeficiency viruses. Immunity. 2012;37(3):399–411. doi: 10.1016/j.immuni.2012.08.013 22999946
44. Malim MH, Bieniasz PD. HIV Restriction Factors and Mechanisms of Evasion. Cold Spring Harbor perspectives in medicine. 2012;2(5):a006940. doi: 10.1101/cshperspect.a006940 22553496
45. Sheehy AM, Gaddis NC, Choi JD, Malim MH. Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein. Nature. 2002;418(6898):646–50. 12167863
46. Marin M, Rose KM, Kozak SL, Kabat D. HIV-1 Vif protein binds the editing enzyme APOBEC3G and induces its degradation. Nat Med. 2003;9(11):1398–403. 14528301
47. Sheehy AM, Gaddis NC, Malim MH. The antiretroviral enzyme APOBEC3G is degraded by the proteasome in response to HIV-1 Vif. Nat Med. 2003;9(11):1404–7. 14528300
48. Stopak K, de Noronha C, Yonemoto W, Greene WC. HIV-1 Vif blocks the antiviral activity of APOBEC3G by impairing both its translation and intracellular stability. Mol Cell. 2003;12(3):591–601. 14527406
49. Müller B, Daecke J, Fackler OT, Dittmar MT, Zentgraf H, Kräusslich H-G. Construction and characterization of a fluorescently labeled infectious human immunodeficiency virus type 1 derivative. J Virol. 2004;78(19):10803–13. 15367647
50. Arfi V, Lienard J, Nguyen XN, Berger G, Rigal D, Darlix JL, et al. Characterization of the behavior of functional viral genomes during the early steps of human immunodeficiency virus type 1 infection. J. Virol. 2009;83(15):7524–35. doi: 10.1128/JVI.00429-09 19457995
51. Corish P, Tyler-Smith C. Attenuation of green fluorescent protein half-life in mammalian cells. Protein engineering. 1999;12(12):1035–40. 10611396
52. Schubert U, Ott DE, Chertova EN, Welker R, Tessmer U, Princiotta MF, et al. Proteasome inhibition interferes with gag polyprotein processing, release, and maturation of HIV-1 and HIV-2. Proc Natl Acad Sci U S A. 2000;97(24):13057–62. 11087859
53. Tritel M, Resh MD. Kinetic analysis of human immunodeficiency virus type 1 assembly reveals the presence of sequential intermediates. J. Virol. 2000;74(13):5845–55. 10846064
54. Ono A, Freed EO. Binding of human immunodeficiency virus type 1 Gag to membrane: role of the matrix amino terminus. J. Virol. 1999;73(5):4136–44. 10196310
55. Jouvenet N, Bieniasz PD, Simon SM. Imaging the biogenesis of individual HIV-1 virions in live cells. Nature. 2008;454(7201):236–40. doi: 10.1038/nature06998 18500329
56. Kutluay SB, Bieniasz PD. Analysis of the initiating events in HIV-1 particle assembly and genome packaging. PLoS Pathogens. 2010;6(11):e1001200. doi: 10.1371/journal.ppat.1001200 21124996
57. Huang M, Orenstein JM, Martin MA, Freed EO. p6Gag is required for particle production from full-length human immunodeficiency virus type 1 molecular clones expressing protease. J. Virol. 1995;69(11):6810–8. 7474093
58. Neil SJD, Zang T, Bieniasz PD. Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu. Nature. 2008;451(7177):425–30. doi: 10.1038/nature06553 18200009
59. Ross TM, Oran AE, Cullen BR. Inhibition of HIV-1 progeny virion release by cell-surface CD4 is relieved by expression of the viral Nef protein. Current Biology. 1999;9(12):613–21. 10375525
60. Rihn SJ, Wilson SJ, Loman NJ, Alim M, Bakker SE, Bhella D, et al. Extreme genetic fragility of the HIV-1 capsid. PLoS Pathogens. 2013;9(6):e1003461. doi: 10.1371/journal.ppat.1003461 23818857
Zvýšte si kvalifikáciu online z pohodlia domova
Nemáte účet? Registrujte sa
Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.
