BCA2/Rabring7 Targets HIV-1 Gag for Lysosomal Degradation in a Tetherin-Independent Manner

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Tetherin (also known as BST2, CD317 or HM1.24) is an interferon-inducible cellular factor that interferes with the release of enveloped viruses from infected cells. A recent study identified BCA2 (Breast Cancer-Associated gene 2, also known as RNF115, ZNF364 or Rabring7), a RING-finger E3 ubiquitin ligase, as a co-factor in the tetherin-mediated restriction of HIV-1. According to this model, BCA2 interacts with sequences in the N-terminus of tetherin to promote the internalization and lysosomal degradation of tethered HIV-1 particles, with no apparent antiviral activity in cells not expressing tetherin. However, here we show for the first time that BCA2 inhibits virus production for HIV-1 and other retroviruses in a tetherin-independent manner by reducing the cellular levels of Gag – the precursor of the structural proteins Matrix, Capsid, Nucleocapsid and p6. Hence, contrary to its reported role as a tetherin co-factor, BCA2 functions as a tetherin-independent antiviral factor that impairs virus assembly and release.

Vyšlo v časopise: BCA2/Rabring7 Targets HIV-1 Gag for Lysosomal Degradation in a Tetherin-Independent Manner. PLoS Pathog 10(5): e32767. doi:10.1371/journal.ppat.1004151
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004151

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Zdroje

1. 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.

2. KirchhoffF (2010) Immune evasion and counteraction of restriction factors by HIV-1 and other primate lentiviruses. Cell Host Microbe 8: 55–67.

3. WolfD, GoffSP (2008) Host restriction factors blocking retroviral replication. Annu Rev Genet 42: 143–163.

4. EvansDT, Serra-MorenoR, SinghRK, GuatelliJC (2010) BST-2/tetherin: a new component of the innate immune response to enveloped viruses. Trends Microbiol 18: 388–396.

5. SheehyAM, GaddisNC, ChoiJD, MalimMH (2002) Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein. Nature 418: 646–650.

6. StremlauM, OwensCM, PerronMJ, KiesslingM, AutissierP, et al. (2004) TRIM5α restricts HIV-1 infection in Old World monkeys. Nature 427: 848–853.

7. HatziioannouT, Perez-CaballeroD, YangA, CowanS, BieniaszPD (2004) Retrovirus resistance factors Ref1 and Lv1 are species-specific variants of TRIM5alpha. Proc Natl Acad Sci U S A 101: 10774–10779.

8. StremlauM, PerronM, WelikalaS, SodroskiJ (2005) Species-specific variation in the B30.2(SPRY) domain of TRIM5a determines the potency of human immunodeficiency virus restriction. J Virol 79: 3139–3145.

9. SongB, JavanbakhtH, PerronM, ParkDH, StremlauM, et al. (2005) Retrovirus restriction by TRIM5a variants from Old World and New World primates. J Virol 79: 3930–3937.

10. YapMW, NicoleS, StoyeJP (2005) A single amino acid in the SPRY domain of human TRIM5alpha leads to HIV-1 restriction. Curr Biol 15: 73–78.

11. LaguetteN, SobhianB, CasartelliN, RingeardM, Chable-BessiaC, et al. (2011) SAMHD1 is the dendritic- and myeloid-cell-specific HIV-1 restriction factor counteracted by Vpx. Nature 474: 654–657.

12. LaguetteN, RahmN, SobhianB, Chable-BessiaC, MunchJ, et al. (2012) Evolutionary and functional analyses of the interaction between the myeloid restriction factor SAMHD1 and the lentiviral Vpx protein. Cell Host Microbe 11: 205–217.

13. HarrisRS, Petersen-MahrtSK, NeubergerMS (2002) RNA editing enzyme APOBEC1 and some of its homologs can act as DNA mutators. Mol Cell 10: 1247–1253.

14. HarrisRS, BishopKN, SheehyAM, CraigHM, Petersen-MahrtSK, et al. (2003) DNA deamination mediates innate immunity to retroviral infection. Cell 113: 803–809.

15. NeilSJ, ZangT, BieniaszPD (2008) Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu. Nature 451: 425–430.

16. Van DammeN, GoffD, KatsuraC, JorgensonRL, MitchellR, et al. (2008) The interferon-induced protein BST-2 restricts HIV-1 release and is downregulated from the cell surface by the viral Vpu protein. Cell Host Microbe 3: 245–252.

17. GoujonC, MoncorgeO, BaubyH, DoyleT, WardCC, et al. (2013) Human MX2 is an interferon-induced post-entry inhibitor of HIV-1 infection. Nature 502: 559–562.

18. LiuZ, PanQ, DingS, QianJ, XuF, et al. (2013) The interferon-inducible MxB protein inhibits HIV-1 infection. Cell Host Microbe 14: 398–410.

19. KaneM, YadavSS, BitzegeioJ, KutluaySB, ZangT, et al. (2013) MX2 is an interferon-induced inhibitor of HIV-1 infection. Nature 502: 563–566.

20. JouvenetN, NeilSJ, ZhadinaM, ZangT, KratovacZ, et al. (2009) Broad-spectrum inhibition of retroviral and filoviral particle release by tetherin. J Virol 83: 1837–1844.

21. Le TortorecA, NeilSJ (2009) Antagonism and intracellular sequestration of human tetherin by the HIV-2 envelope glycoprotein. J Virol 83: 11966–11978.

22. JiaB, Serra-MorenoR, NeidermyerW, RahmbergA, MackeyJ, et al. (2009) Species-specific activity of SIV Nef and HIV-1 Vpu in overcoming restriction by tetherin/BST2. PLoS Pathog 5: e1000429.

23. ZhangF, WilsonSJ, LandfordWC, VirgenB, GregoryD, et al. (2009) Nef proteins from simian immunodeficiency viruses are tetherin antagonists. Cell Host Microbe 6: 54–67.

24. SauterD, SchindlerM, SpechtA, LandfordWN, MunchJ, et al. (2009) Tetherin-driven adaptation of Vpu and Nef function and the evolution of pandemic and nonpandemic HIV-1 strains. Cell Host Microbe 6: 409–421.

25. Serra-MorenoR, ZimmermannK, SternLJ, EvansDT (2013) Tetherin/BST-2 Antagonism by Nef Depends on a Direct Physical Interaction between Nef and Tetherin, and on Clathrin-mediated Endocytosis. PLoS Pathog 9: e1003487.

26. ZhangF, LandfordWN, NgM, McNattMW, BieniaszPD, et al. (2011) SIV Nef proteins recruit the AP-2 complex to antagonize Tetherin and facilitate virion release. PLoS Pathog 7: e1002039.

27. MiyakawaK, RyoA, MurakamiT, OhbaK, YamaokaS, et al. (2009) BCA2/Rabring7 promotes tetherin-dependent HIV-1 restriction. PLoS Pathog 5: e1000700.

28. MizunoK, KitamuraA, SasakiT (2003) Rabring7, a novel Rab7 target protein with a RING finger motif. Mol Biol Cell 14: 3741–3752.

29. Serra-MorenoR, JiaB, BreedM, AlvarezX, EvansDT (2011) Compensatory Changes in the Cytoplasmic Tail of gp41 Confer Resistance to Tetherin/BST-2 in a Pathogenic Nef-Deleted SIV. Cell Host Microbe 9: 46–57.

30. GoffinetC, SchmidtS, KernC, OberbremerL, KepplerOT (2010) Endogenous CD317/Tetherin limits replication of HIV-1 and murine leukemia virus in rodent cells and is resistant to antagonists from primate viruses. J Virol 84: 11374–11384.

31. AmemiyaY, AzmiP, SethA (2008) Autoubiquitination of BCA2 RING E3 ligase regulates its own stability and affects cell migration. Mol Cancer Res: MCR 6: 1385–1396.

32. BurgerAM, GaoY, AmemiyaY, KahnHJ, KitchingR, et al. (2005) A novel RING-type ubiquitin ligase breast cancer-associated gene 2 correlates with outcome in invasive breast cancer. Cancer Res 65: 10401–10412.

33. BacopulosS, AmemiyaY, YangW, ZubovitsJ, BurgerA, et al. (2012) Effects of partner proteins on BCA2 RING ligase activity. BMC Cancer 12: 63.

34. BrahemiG, KonaFR, FiasellaA, BuacD, SoukupovaJ, et al. (2010) Exploring the structural requirements for inhibition of the ubiquitin E3 ligase breast cancer associated protein 2 (BCA2) as a treatment for breast cancer. J Med Chem 53: 2757–2765.

35. 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.

36. NaardingMA, BaanE, PollakisG, PaxtonWA (2007) Effect of chloroquine on reducing HIV-1 replication in vitro and the DC-SIGN mediated transfer of virus to CD4+ T-lymphocytes. Retrovirology 4: 6.

37. SavarinoA, GenneroL, SperberK, BoelaertJR (2001) The anti-HIV-1 activity of chloroquine. J Clin Virol 20: 131–135.

38. SavarinoA, GenneroL, ChenHC, SerranoD, MalavasiF, et al. (2001) Anti-HIV effects of chloroquine: mechanisms of inhibition and spectrum of activity. AIDS 15: 2221–2229.

39. ChiangG, SassaroliM, LouieM, ChenH, StecherVJ, et al. (1996) Inhibition of HIV-1 replication by hydroxychloroquine: mechanism of action and comparison with zidovudine. Clin Ther 18: 1080–1092.

40. AlexanderL, DuZ, RosenzweigM, JungJU, DesrosiersRC (1997) A role for natural simian immunodeficiency virus and human immunodeficiency virus type 1 nef alleles in lymphocyte activation. J Virol 71: 6094–6099.

41. HatziioannouT, Perez-CaballeroD, YangA, CowanS, BieniaszPD (2004) Retrovirus resistance factors Ref1 and Lv1 are species-specific variants of TRIM5α. Proc Natl Acad Sci U S A 101: 10774–10779.

42. SakaneA, HatakeyamaS, SasakiT (2007) Involvement of Rabring7 in EGF receptor degradation as an E3 ligase. Biochem Biophys Res Comm 357: 1058–1064.

43. SmithCJ, BerryDM, McGladeCJ (2013) The E3 ubiquitin ligases RNF126 and Rabring7 regulate endosomal sorting of the epidermal growth factor receptor. J Cell Sci 126: 1366–1380.

44. SmirnovaEV, CollingwoodTS, BisbalC, TsygankovaOM, BogushM, et al. (2008) TULA proteins bind to ABCE-1, a host factor of HIV-1 assembly, and inhibit HIV-1 biogenesis in a UBA-dependent fashion. Virology 372: 10–23.

45. Hermida-MatsumotoL, ReshMD (2000) Localization of human immunodeficiency virus type 1 Gag and Env at the plasma membrane by confocal imaging. J Virol 74: 8670–8679.

46. KestlerHW, RinglerDJ, MoriK, PanicaliDL, SehgalPK, et al. (1991) Importance of the nef gene for maintenance of high virus loads and for the development of AIDS. Cell 65: 651–662.

47. RegierDA, DesrosiersRC (1990) The complete nucleotide sequence of a pathogenic molecular clone of simian immunodeficiency virus. AIDS Res Hum Retro 6: 1221–1231.