Tetherin Can Restrict Cell-Free and Cell-Cell Transmission of HIV from Primary Macrophages to T Cells

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Tetherin is a cellular protein that inhibits (or restricts) a broad range of enveloped viruses, including HIV, by physically “tethering” nascent particles to the plasma membrane of infected cells. CD4+ T cells and macrophages are the main targets of HIV in vivo, and both cell types express Tetherin. Although the mechanisms of Tetherin-mediated restriction in model cell lines and T cells are increasingly well understood, experimental data from macrophages are sparse, and partially contradict observations made in other cell types. Here we investigate the sensitivity of Tetherin expression to interferon, and the subcellular localisation of the restriction factor in primary human macrophages. We find that Tetherin inhibits HIV release by retaining nascent particles in macrophage HIV assembly compartments, and can also restrict the transmission of HIV across intercellular contacts between macrophages and T cells. Finally, we demonstrate that the HIV protein Vpu efficiently counteracts Tetherin in macrophages, and thereby ensures viral propagation. Our results, together with other published data, show that Tetherin can efficiently inhibit viral replication in both major target cell types of HIV, regardless of the mode of transmission. These data support the view that efficient counteraction of Tetherin was a crucial factor for the global spread of HIV.

Vyšlo v časopise: Tetherin Can Restrict Cell-Free and Cell-Cell Transmission of HIV from Primary Macrophages to T Cells. PLoS Pathog 10(7): e32767. doi:10.1371/journal.ppat.1004189
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004189

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Zdroje

1. YanN, ChenZJ (2012) Intrinsic antiviral immunity. Nat Immunol 13 : 214–222.

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

3. 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.

4. 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.

5. RollasonR, KorolchukV, HamiltonC, SchuP, BantingG (2007) Clathrin-mediated endocytosis of a lipid-raft-associated protein is mediated through a dual tyrosine motif. J Cell Sci 120 : 3850–3858.

6. MasuyamaN, KuronitaT, TanakaR, MutoT, HirotaY, et al. (2009) HM1.24 is internalized from lipid rafts by clathrin-mediated endocytosis through interaction with alpha-adaptin. J Biol Chem 284 : 15927–15941.

7. Perez-CaballeroD, ZangT, EbrahimiA, McNattMW, GregoryDA, et al. (2009) Tetherin inhibits HIV-1 release by directly tethering virions to cells. Cell 139 : 499–511.

8. HammondsJ, WangJ-J, YiH, SpearmanP (2010) Immunoelectron microscopic evidence for Tetherin/BST2 as the physical bridge between HIV-1 virions and the plasma membrane. PLoS Pathog 6: e1000749.

9. VenkateshS, BieniaszPD (2013) Mechanism of HIV-1 Virion Entrapment by Tetherin. PLoS Pathog 9: e1003483.

10. CailletM, JanvierK, Pelchen-MatthewsA, Delcroix-GenêteD, CamusG, et al. (2011) Rab7A is required for efficient production of infectious HIV-1. PLoS Pathog 7: e1002347.

11. JanvierK, Pelchen-MatthewsA, RenaudJ-B, CailletM, MarshM, et al. (2011) The ESCRT-0 component HRS is required for HIV-1 Vpu-mediated BST-2/tetherin down-regulation. PLoS Pathog 7: e1001265.

12. MitchellRS, KatsuraC, SkaskoMA, FitzpatrickK, LauD, et al. (2009) Vpu antagonizes BST-2-mediated restriction of HIV-1 release via beta-TrCP and endo-lysosomal trafficking. PLoS Pathog 5: e1000450.

13. SattentauQJ (2011) The direct passage of animal viruses between cells. Curr Opin Virol 1 : 396–402.

14. JollyC, KashefiK, HollinsheadM, SattentauQJ (2004) HIV-1 cell to cell transfer across an Env-induced, actin-dependent synapse. J Exp Med 199 : 283–293.

15. GrootF, WelschS, SattentauQJ (2008) Efficient HIV-1 transmission from macrophages to T cells across transient virological synapses. Blood 111 : 4660–4663.

16. GoussetK, AblanSD, CorenLV, OnoA, SoheilianF, et al. (2008) Real-time visualization of HIV-1 GAG trafficking in infected macrophages. PLoS Pathog 4: e1000015.

17. CasartelliN, SourisseauM, FeldmannJ, Guivel-BenhassineF, MalletA, et al. (2010) Tetherin restricts productive HIV-1 cell-to-cell transmission. PLoS Pathog 6: e1000955.

18. JollyC, BoothNJ, NeilSJD (2010) Cell-cell spread of human immunodeficiency virus type 1 overcomes tetherin/BST-2-mediated restriction in T cells. J Virol 84 : 12185–12199.

19. KuhlBD, SloanRD, DonahueDA, Bar-MagenT, LiangC, et al. (2010) Tetherin restricts direct cell-to-cell infection of HIV-1. Retrovirology 7 : 115.

20. ColemanCM, SpearmanP, WuL (2011) Tetherin does not significantly restrict dendritic cell-mediated HIV-1 transmission and its expression is upregulated by newly synthesized HIV-1 Nef. Retrovirology 8 : 26.

21. ChuH, WangJ-J, QiM, YoonJ-J, ChenX, et al. (2012) Tetherin/BST-2 Is Essential for the Formation of the Intracellular Virus-Containing Compartment in HIV-Infected Macrophages. Cell Host Microbe 12 : 360–372.

22. BlanchetFP, StalderR, CzubalaM, LehmannM, RioL, et al. (2013) TLR-4 engagement of dendritic cells confers a BST-2/tetherin-mediated restriction of HIV-1 infection to CD4+ T cells across the virological synapse. Retrovirology 10 : 6.

23. ZhongP, AgostoLM, IlinskayaA, DorjbalB, TruongR, et al. (2013) Cell-to-Cell Transmission Can Overcome Multiple Donor and Target Cell Barriers Imposed on Cell-Free HIV. PloS One 8: e53138.

24. DenekaM, Pelchen-MatthewsA, BylandR, Ruiz-MateosE, MarshM (2007) In macrophages, HIV-1 assembles into an intracellular plasma membrane domain containing the tetraspanins CD81, CD9, and CD53. J Cell Biol 177 : 329–341.

25. WelschS, KepplerOT, HabermannA, AllespachI, Krijnse-LockerJ, et al. (2007) HIV-1 buds predominantly at the plasma membrane of primary human macrophages. PLoS Pathog 3: e36.

26. Pelchen-MatthewsA, GieseS, MlcochovaP, TurnerJ, MarshM (2012) β2 integrin adhesion complexes maintain the integrity of HIV-1 assembly compartments in primary macrophages. Traffic 13 : 273–291.

27. JouveM, Sol-FoulonN, WatsonS, SchwartzO, BenarochP (2007) HIV-1 buds and accumulates in “nonacidic” endosomes of macrophages. Cell Host Microbe 2 : 85–95.

28. MlcochovaP, Pelchen-MatthewsA, MarshM (2013) Organization and regulation of intracellular plasma membrane-connected HIV-1 assembly compartments in macrophages. BMC Biol 11 : 89.

29. WelschS, GrootF, KräusslichH-G, KepplerOT, SattentauQJ (2011) Architecture and regulation of the HIV-1 assembly and holding compartment in macrophages. J Virol 85 : 7922–7927.

30. MiyagiE, AndrewAJ, KaoS, StrebelK (2009) Vpu enhances HIV-1 virus release in the absence of Bst-2 cell surface down-modulation and intracellular depletion. Proc Natl Acad Sci USA 106 : 2868–2873.

31. SchubertU, BourS, WilleyRL, StrebelK (1999) Regulation of virus release by the macrophage-tropic human immunodeficiency virus type 1 AD8 isolate is redundant and can be controlled by either Vpu or Env. J Virol 73 : 887–896.

32. RasaiyaahJ, TanCP, FletcherAJ, PriceAJ, BlondeauC, et al. (2013) HIV-1 evades innate immune recognition through specific cofactor recruitment. Nature 503 : 402–405.

33. PlantierJ-C, LeozM, DickersonJE, De OliveiraF, CordonnierF, et al. (2009) A new human immunodeficiency virus derived from gorillas. Nat Med 15 : 871–872.

34. SauterD, HuéS, PetitSJ, PlantierJ-C, TowersGJ, et al. (2011) HIV-1 Group P is unable to antagonize human tetherin by Vpu, Env or Nef. Retrovirology 8 : 103.

35. YangSJ, LopezLA, ExlineCM, HaworthKG, CannonPM (2011) Lack of adaptation to human tetherin in HIV-1 group O and P. Retrovirology 8 : 78.

36. GalãoRP, Le TortorecA, PickeringS, KueckT, NeilSJD (2012) Innate sensing of HIV-1 assembly by Tetherin induces NFκB-dependent proinflammatory responses. Cell Host Microbe 12 : 633–644.

37. CockaLJ, BatesP (2012) Identification of alternatively translated tetherin isoforms with differing antiviral and signaling activities. PLoS Pathog 8: e1002931.

38. KoppensteinerH, Brack-WernerR, SchindlerM (2012) Macrophages and their relevance in Human Immunodeficiency Virus Type I infection. Retrovirology 9 : 82.

39. GaudinR, BèrreS, Cunha de AlencarB, DecalfJ, SchindlerM, et al. (2013) Dynamics of HIV-containing compartments in macrophages reveal sequestration of virions and transient surface connections. PLoS ONE 8: e69450.

40. KoppensteinerH, BanningC, SchneiderC, HohenbergH, SchindlerM (2012) Macrophage internal HIV-1 is protected from neutralizing antibodies. J Virol 86 : 2826–2836.

41. ChuH, WangJ-J, QiM, YoonJ-J, WenX, et al. (2012) The intracellular virus-containing compartments in primary human macrophages are largely inaccessible to antibodies and small molecules. PLoS ONE 7: e35297.

42. CooperA, GarcíaM, PetrovasC, YamamotoT, KoupRA, et al. (2013) HIV-1 causes CD4 cell death through DNA-dependent protein kinase during viral integration. Nature 498 : 376–379.

43. DoitshG, CavroisM, LassenKG, ZepedaO, YangZ, et al. (2010) Abortive HIV infection mediates CD4 T cell depletion and inflammation in human lymphoid tissue. Cell 143 : 789–801.

44. LepelleyA, LouisS, SourisseauM, LawHKW, PothlichetJ, et al. (2011) Innate sensing of HIV-infected cells. PLoS Pathog 7: e1001284.

45. SchindlerM, RajanD, BanningC, WimmerP, KoppensteinerH, et al. (2010) Vpu serine 52 dependent counteraction of tetherin is required for HIV-1 replication in macrophages, but not in ex vivo human lymphoid tissue. Retrovirology 7 : 1.

46. GummuluruS, KinseyCM, EmermanM (2000) An In Vitro Rapid-Turnover Assay for Human Immunodeficiency Virus Type 1 Replication Selects for Cell-to-Cell Spread of Virus. J Virol 74 : 10882–10891.

47. NolanKM, JordanAPO, HoxieJA (2008) Effects of partial deletions within the human immunodeficiency virus type 1 V3 loop on coreceptor tropism and sensitivity to entry inhibitors. J Virol 82 : 664–673.

48. Pelchen-MatthewsA, KramerB, MarshM (2003) Infectious HIV-1 assembles in late endosomes in primary macrophages. J Cell Biol 162 : 443–455.

49. CassolE, CassettaL, RizziC, AlfanoM, PoliG (2009) M1 and M2a polarization of human monocyte-derived macrophages inhibits HIV-1 replication by distinct mechanisms. J Immunol 182 : 6237–6246.