Functions of CPSF6 for HIV-1 as Revealed by HIV-1 Capsid Evolution in HLA-B27-Positive Subjects

English version České info

The host protein CPSF6 possesses a domain that can interact with the HIV-1 capsid (CA) protein. CPSF6 has been implicated in regulating HIV-1 nuclear entry. However, its functional significance for HIV-1 replication has yet to be firmly established. Here we provide evidence for two divergent functions of CPSF6 for HIV-1 replication in vivo. We demonstrate that endogenous CPSF6 exerts an inhibitory effect on naturally occurring HIV-1 variants in individuals carrying the HLA-B27 allele. Conversely, we find a strong selective pressure in these individuals to preserve CPSF6 binding, while escaping from the restrictive activity by CPSF6. This active maintenance of CPSF6 binding during HIV-1 CA evolution in vivo contrasts with the in vitro viral evolution, which can reduce CPSF6 binding to evade from CPSF6-mediated restriction. Thus, these observations argue for a beneficial role of CPSF6 for HIV-1 in vivo. CPSF6-mediated restriction renders HIV-1 less dependent or independent from TNPO3, RanBP2 and Nup153, host factors implicated in HIV-1 nuclear entry. However, viral evolution that maintains CPSF6 binding in HLA-B27+ subjects invariably restores the ability to utilize these host factors, which may be the major selective pressure for CPSF6 binding in vivo. Our study uncovers two opposing CA-dependent functions of CPSF6 in HIV-1 replication in vivo; however, the benefit for binding CPSF6 appears to outweigh the cost, providing support for a vital function of CPSF6 during HIV-1 replication in vivo.

Vyšlo v časopise: Functions of CPSF6 for HIV-1 as Revealed by HIV-1 Capsid Evolution in HLA-B27-Positive Subjects. PLoS Pathog 10(1): e32767. doi:10.1371/journal.ppat.1003868
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1003868

Souhrn

Zdroje

1. KatzRA, GregerJG, SkalkaAM (2005) Effects of cell cycle status on early events in retroviral replication. J Cell Biochem 94 : 880–889.

2. FassatiA (2006) HIV infection of non-dividing cells: a divisive problem. Retrovirology 3 : 74.

3. YamashitaM, EmermanM (2006) Retroviral infection of non-dividing cells: old and new perspectives. Virology 344 : 88–93.

4. GoffSP (2007) Host factors exploited by retroviruses. Nat Rev Microbiol 5 : 253–263.

5. BushmanFD, MalaniN, FernandesJ, D'OrsoI, CagneyG, et al. (2009) Host cell factors in HIV replication: meta-analysis of genome-wide studies. PLoS Pathog 5: e1000437.

6. RiviereL, DarlixJL, CimarelliA (2010) Analysis of the viral elements required in the nuclear import of HIV-1 DNA. J Virol 84 : 729–739.

7. ShahVB, AikenC (2010) HIV Nuclear Entry: Clearing the Fog. Viruses 2 : 1190–1194.

8. VatakisDN, NixonCC, ZackJA (2010) Quiescent T cells and HIV: an unresolved relationship. Immunol Res 48 : 110–121.

9. PaceMJ, AgostoL, GrafEH, O'DohertyU (2011) HIV reservoirs and latency models. Virology 411 : 344–354.

10. Le DouceV, HerbeinG, RohrO, SchwartzC (2010) Molecular mechanisms of HIV-1 persistence in the monocyte-macrophage lineage. Retrovirology 7 : 32.

11. YamashitaM, EmermanM (2004) Capsid is a dominant determinant of retrovirus infectivity in nondividing cells. J Virol 78 : 5670–5678.

12. RoeT, ReynoldsTC, YuG, BrownPO (1993) Integration of murine leukemia virus DNA depends on mitosis. Embo J 12 : 2099–2108.

13. LewisPF, EmermanM (1994) Passage through mitosis is required for oncoretroviruses but not for the human immunodeficiency virus. J Virol 68 : 510–516.

14. ElisE, EhrlichM, Prizan-RavidA, Laham-KaramN, BacharachE (2013) p12 tethers the murine leukemia virus pre-integration complex to mitotic chromosomes. PLoS Pathog 8: e1003103.

15. von SchwedlerUK, StrayKM, GarrusJE, SundquistWI (2003) Functional surfaces of the human immunodeficiency virus type 1 capsid protein. J Virol 77 : 5439–5450.

16. DismukeDJ, AikenC (2006) Evidence for a functional link between uncoating of the human immunodeficiency virus type 1 core and nuclear import of the viral preintegration complex. J Virol 80 : 3712–3720.

17. KrishnanL, MatreyekKA, OztopI, LeeK, TipperCH, et al. (2010) The Requirement for Cellular Transportin 3 (TNPO3 or TRN-SR2) during Infection Maps to Human Immunodeficiency Virus Type 1 Capsid and Not Integrase. Journal of Virology 84 : 397–406.

18. LeeK, AmbroseZ, MartinTD, OztopI, MulkyA, et al. (2010) Flexible use of nuclear import pathways by HIV-1. Cell Host Microbe 7 : 221–233.

19. SchallerT, OcwiejaKE, RasaiyaahJ, PriceAJ, BradyTL, et al. (2011) HIV-1 Capsid-Cyclophilin Interactions Determine Nuclear Import Pathway, Integration Targeting and Replication Efficiency. PLoS Pathog 7: e1002439.

20. BrassAL, DykxhoornDM, BenitaY, YanN, EngelmanA, et al. (2008) Identification of host proteins required for HIV infection through a functional genomic screen. Science 319 : 921–926.

21. KönigR, ZhouY, EllederD, DiamondT, BonamyG, et al. (2008) Global Analysis of Host-Pathogen Interactions that Regulate Early-Stage HIV-1 Replication. Cell 135 : 49–60.

22. ZhouH, XuM, HuangQ, GatesAT, ZhangXD, et al. (2008) Genome-Scale RNAi Screen for Host Factors Required for HIV Replication. Cell Host & Microbe 4 : 495–504.

23. ChristF, ThysW, De RijckJ, GijsbersR, AlbaneseA, et al. (2008) Transportin-SR2 imports HIV into the nucleus. Curr Biol 18 : 1192–1202.

24. De IacoA, LubanJ (2011) Inhibition of HIV-1 infection by TNPO3 depletion is determined by capsid and detectable after viral cDNA enters the nucleus. Retrovirology 8 : 98.

25. LogueEC, TaylorKT, GoffPH, LandauNR (2011) The Cargo-Binding Domain of Transportin 3 Is Required for Lentivirus Nuclear Import. Journal of Virology 85 : 12950–12961.

26. MatreyekKA, EngelmanA (2011) The Requirement for Nucleoporin NUP153 during Human Immunodeficiency Virus Type 1 Infection Is Determined by the Viral Capsid. Journal of Virology 85 : 7818–7827.

27. ZhouL, SokolskajaE, JollyC, JamesW, CowleySA, et al. (2011) Transportin 3 Promotes a Nuclear Maturation Step Required for Efficient HIV-1 Integration. PLoS Pathog 7: e1002194.

28. Valle-CasusoJC, Di NunzioF, YangY, ReszkaN, LienlafM, et al. (2012) TNPO3 Is Required for HIV-1 Replication after Nuclear Import but prior to Integration and Binds the HIV-1 Core. Journal of Virology 86 : 5931–5936.

29. Di NunzioF, DanckaertA, FrickeT, PerezP, FernandezJ, et al. (2012) Human Nucleoporins Promote HIV-1 Docking at the Nuclear Pore, Nuclear Import and Integration. PLoS ONE 7: e46037.

30. Di NunzioF, FrickeT, MiccioA, Valle-CasusoJC, PerezP, et al. (2013) Nup153 and Nup98 bind the HIV-1 core and contribute to the early steps of HIV-1 replication. Virology 440 : 8–18.

31. Diaz-GrifferoF (2012) The Role of TNPO3 in HIV-1 Replication. Mol Biol Int 2012 : 868597.

32. LubanJ (2007) Cyclophilin A, TRIM5, and resistance to human immunodeficiency virus type 1 infection. J Virol 81 : 1054–1061.

33. TowersGJ (2007) The control of viral infection by tripartite motif proteins and cyclophilin A. Retrovirology 4 : 40.

34. ShahVB, ShiJ, HoutDR, OztopI, KrishnanL, et al. (2013) The host proteins transportin SR2/TNPO3 and cyclophilin A exert opposing effects on HIV-1 uncoating. J Virol 87 : 422–432.

35. De IacoA, SantoniF, VannierA, GuipponiM, AntonarakisS, et al. (2013) TNPO3 protects HIV-1 replication from CPSF6-mediated capsid stabilization in the host cell cytoplasm. Retrovirology 10 : 20.

36. PriceAJ, FletcherAJ, SchallerT, ElliottT, LeeK, et al. (2012) CPSF6 defines a conserved capsid interface that modulates HIV-1 replication. PLoS Pathog 8: e1002896.

37. FrickeT, Valle-CasusoJC, WhiteTE, Brandariz-NunezA, BoscheWJ, et al. (2013) The ability of TNPO3-depleted cells to inhibit HIV-1 infection requires CPSF6. Retrovirology 10 : 46.

38. YamashitaM, PerezO, HopeTJ, EmermanM (2007) Evidence for direct involvement of the capsid protein in HIV infection of nondividing cells. PLoS Pathog 3 : 1502–1510.

39. QiM, YangR, AikenC (2008) Cyclophilin A-dependent restriction of human immunodeficiency virus type 1 capsid mutants for infection of nondividing cells. J Virol 82 : 12001–12008.

40. YamashitaM, EmermanM (2009) Cellular Restriction Targeting Viral Capsids Perturbs Human Immunodeficiency Virus Type 1 Infection of Nondividing Cells. Journal of Virology 83 : 9835–9843.

41. YlinenLM, SchallerT, PriceA, FletcherAJ, NoursadeghiM, et al. (2009) Cyclophilin A levels dictate infection efficiency of human immunodeficiency virus type 1 capsid escape mutants A92E and G94D. J Virol 83 : 2044–2047.

42. SongC, AikenC (2007) Analysis of human cell heterokaryons demonstrates that target cell restriction of cyclosporine-resistant human immunodeficiency virus type 1 mutants is genetically dominant. J Virol 81 : 11946–11956.

43. SchneidewindA, BrockmanMA, YangR, AdamRI, LiB, et al. (2007) Escape from the dominant HLA-B27-restricted cytotoxic T-lymphocyte response in Gag is associated with a dramatic reduction in human immunodeficiency virus type 1 replication. J Virol 81 : 12382–12393.

44. YangR, AikenC (2007) A mutation in alpha helix 3 of CA renders human immunodeficiency virus type 1 cyclosporin A resistant and dependent: rescue by a second-site substitution in a distal region of CA. J Virol 81 : 3749–3756.

45. GoulderPJ, BranderC, TangY, TremblayC, ColbertRA, et al. (2001) Evolution and transmission of stable CTL escape mutations in HIV infection. Nature 412 : 334–338.

46. LiY, KarAK, SodroskiJ (2009) Target cell type-dependent modulation of human immunodeficiency virus type 1 capsid disassembly by cyclophilin A. J Virol 83 : 10951–10962.

47. LeeK, MulkyA, YuenW, MartinTD, MeyersonNR, et al. (2012) HIV-1 capsid-targeting domain of cleavage and polyadenylation specificity factor 6. J Virol 86 : 3851–3860.

48. AmbroseZ, LeeK, NdjomouJ, XuH, OztopI, et al. (2012) Human immunodeficiency virus type 1 capsid mutation N74D alters cyclophilin A dependence and impairs macrophage infection. J Virol 86 : 4708–4714.

49. WangYE, LiB, CarlsonJM, StreeckH, GladdenAD, et al. (2009) Protective HLA Class I Alleles That Restrict Acute-Phase CD8+ T-Cell Responses Are Associated with Viral Escape Mutations Located in Highly Conserved Regions of Human Immunodeficiency Virus Type 1. Journal of Virology 83 : 1845–1855.

50. LubanJ (1996) Absconding with the chaperone: essential cyclophilin-Gag interaction in HIV-1 virions. Cell 87 : 1157–1159.

51. SokolskajaE, SayahDM, LubanJ (2004) Target cell cyclophilin A modulates human immunodeficiency virus type 1 infectivity. J Virol 78 : 12800–12808.

52. HatziioannouT, Perez-CaballeroD, CowanS, BieniaszPD (2005) Cyclophilin interactions with incoming human immunodeficiency virus type 1 capsids with opposing effects on infectivity in human cells. J Virol 79 : 176–183.

53. BattivelliE, MigraineJ, LecossierD, YeniP, ClavelF, et al. (2011) Gag Cytotoxic T Lymphocyte Escape Mutations Can Increase Sensitivity of HIV-1 to Human TRIM5α, Linking Intrinsic and Acquired Immunity. Journal of Virology 85 : 11846–11854.

54. DahirelV, ShekharK, PereyraF, MiuraT, ArtyomovM, et al. (2011) Coordinate linkage of HIV evolution reveals regions of immunological vulnerability. Proc Natl Acad Sci U S A 108 : 11530–11535.

55. RihnS, WilsonS, LomanN, AlimM, GiffordR, et al. (2013) Extreme genetic fragility of the HIV-1 capsid. PLoS Pathog 9: e1003461.

56. BlairWS, PickfordC, IrvingSL, BrownDG, AndersonM, et al. (2010) HIV capsid is a tractable target for small molecule therapeutic intervention. PLoS Pathog 6: e1001220.

57. ShiJ, ZhouJ, ShahVB, AikenC, WhitbyK (2011) Small-molecule inhibition of human immunodeficiency virus type 1 infection by virus capsid destabilization. J Virol 85 : 542–549.

58. JagerS, CimermancicP, GulbahceN, JohnsonJR, McGovernKE, et al. (2011) Global landscape of HIV-human protein complexes. Nature 481 : 365–370.

59. GanserBK, LiS, KlishkoVY, FinchJT, SundquistWI (1999) Assembly and analysis of conical models for the HIV-1 core. Science 283 : 80–83.

60. BraatenD, LubanJ (2001) Cyclophilin A regulates HIV-1 infectivity, as demonstrated by gene targeting in human T cells. Embo J 20 : 1300–1309.

61. KratovacZ, VirgenCA, Bibollet-RucheF, HahnBH, BieniaszPD, et al. (2008) Primate lentivirus capsid sensitivity to TRIM5 proteins. J Virol 82 : 6772–6777.

62. StremlauM, PerronM, LeeM, LiY, SongB, et al. (2006) Specific recognition and accelerated uncoating of retroviral capsids by the TRIM5alpha restriction factor. Proc Natl Acad Sci U S A 103 : 5514–5519.

63. PornillosO, Ganser-PornillosBK, BanumathiS, HuaY, YeagerM (2010) Disulfide bond stabilization of the hexameric capsomer of human immunodeficiency virus. J Mol Biol 401 : 985–995.