BST2/Tetherin Enhances Entry of Human Cytomegalovirus
Interferon-induced BST2/Tetherin prevents budding of vpu-deficient HIV-1 by tethering mature viral particles to the plasma membrane. BST2 also inhibits release of other enveloped viruses including Ebola virus and Kaposi's sarcoma associated herpesvirus (KSHV), indicating that BST2 is a broadly acting antiviral host protein. Unexpectedly however, recovery of human cytomegalovirus (HCMV) from supernatants of BST2-expressing human fibroblasts was increased rather than decreased. Furthermore, BST2 seemed to enhance viral entry into cells since more virion proteins were released into BST2-expressing cells and subsequent viral gene expression was elevated. A significant increase in viral entry was also observed upon induction of endogenous BST2 during differentiation of the pro-monocytic cell line THP-1. Moreover, treatment of primary human monocytes with siRNA to BST2 reduced HCMV infection, suggesting that BST2 facilitates entry of HCMV into cells expressing high levels of BST2 either constitutively or in response to exogenous stimuli. Since BST2 is present in HCMV particles we propose that HCMV entry is enhanced via a reverse-tethering mechanism with BST2 in the viral envelope interacting with BST2 in the target cell membrane. Our data suggest that HCMV not only counteracts the well-established function of BST2 as inhibitor of viral egress but also employs this anti-viral protein to gain entry into BST2-expressing hematopoietic cells, a process that might play a role in hematogenous dissemination of HCMV.
Vyšlo v časopise:
BST2/Tetherin Enhances Entry of Human Cytomegalovirus. PLoS Pathog 7(11): e32767. doi:10.1371/journal.ppat.1002332
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1002332
Souhrn
Interferon-induced BST2/Tetherin prevents budding of vpu-deficient HIV-1 by tethering mature viral particles to the plasma membrane. BST2 also inhibits release of other enveloped viruses including Ebola virus and Kaposi's sarcoma associated herpesvirus (KSHV), indicating that BST2 is a broadly acting antiviral host protein. Unexpectedly however, recovery of human cytomegalovirus (HCMV) from supernatants of BST2-expressing human fibroblasts was increased rather than decreased. Furthermore, BST2 seemed to enhance viral entry into cells since more virion proteins were released into BST2-expressing cells and subsequent viral gene expression was elevated. A significant increase in viral entry was also observed upon induction of endogenous BST2 during differentiation of the pro-monocytic cell line THP-1. Moreover, treatment of primary human monocytes with siRNA to BST2 reduced HCMV infection, suggesting that BST2 facilitates entry of HCMV into cells expressing high levels of BST2 either constitutively or in response to exogenous stimuli. Since BST2 is present in HCMV particles we propose that HCMV entry is enhanced via a reverse-tethering mechanism with BST2 in the viral envelope interacting with BST2 in the target cell membrane. Our data suggest that HCMV not only counteracts the well-established function of BST2 as inhibitor of viral egress but also employs this anti-viral protein to gain entry into BST2-expressing hematopoietic cells, a process that might play a role in hematogenous dissemination of HCMV.
Zdroje
1. EmeryVC 2001 Investigation of CMV disease in immunocompromised patients. J Clin Pathol 54 84 88
2. ScholzMDoerrHWCinatJ 2003 Human cytomegalovirus retinitis: pathogenicity, immune evasion and persistence. Trends Microbiol 11 171 177
3. GriffithsPDWalterS 2005 Cytomegalovirus. Curr Opin Infect Dis 18 241 245
4. StreblowDNOrloffSLNelsonJA 2001 Do pathogens accelerate atherosclerosis. J Nutr 131 2798S 2804S
5. Soderberg-NauclerC 2008 HCMV microinfections in inflammatory diseases and cancer. J Clin Virol 41 218 223
6. SweetC 1999 The pathogenicity of cytomegalovirus. FEMS Microbiol Rev 23 457 482
7. ComptonT 2004 Receptors and immune sensors: the complex entry path of human cytomegalovirus. Trends Cell Biol 14 5 8
8. RyckmanBJJarvisMADrummondDDNelsonJAJohnsonDC 2006 Human Cytomegalovirus entry into epithelial and endothelial cells depends on genes UL128 to UL150 and occurs by endocytosis and low-pH fusion. J Virol 80 710 722
9. SinzgerC 2008 Entry route of HCMV into endothelial cells. J Clin Virol 41 174 179
10. GotoTKennelSJAbeMTakishitaMKosakaM 1994 A novel membrane antigen selectively expressed on terminally differentiated human B cells. Blood 84 1922 1930
11. BlasiusALGiurisatoECellaMSchreiberRDShawAS 2006 Bone marrow stromal cell antigen 2 is a specific marker of type I IFN-producing cells in the naive mouse, but a promiscuous cell surface antigen following IFN stimulation. J Immunol 177 3260 3265
12. CaoWBoverLChoMWenXHanabuchiS 2009 Regulation of TLR7/9 responses in plasmacytoid dendritic cells by BST2 and ILT7 receptor interaction. J Exp Med 206 1603 1614
13. BarteeEMcCormackAFruhK 2006 Quantitative membrane proteomics reveals new cellular targets of viral immune modulators. PLoS Pathog 2 e107
14. MansouriMViswanathanKDouglasJLHinesJGustinJ 2009 Molecular mechanism of BST2/Tetherin downregulation by K5/MIR2 of Kaposi's sarcoma-associated herpesvirus. J Virol 83 9672 9681
15. NeilSJDZangTBieniaszPD 2008 Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu. Nature 451 425 430
16. DammeNVGoffDKatsuraCJorgensonRLMitchellR 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 1 8
17. DouglasJLViswanathanKMcCarrollMNGustinJKFruhK 2009 Vpu directs the degradation of the human Immunodeficiency virus restriction factor BST-2/Tetherin via a beta TrCP-dependent mechanism. J Virol 83 7931 7947
18. SchubertUAntonLCBacikICoxJHBourS 1998 CD4 glycoprotein degradation induced by human immunodeficiency virus type 1 Vpu protein requires the function of proteasomes and the ubiquitin-conjugating pathway. J Virol 72 2280 2288
19. DouglasJLGustinJKViswanathanKMansouriMMosesAV 2010 The great escape: viral strategies to counter BST-2/Tetherin. PLoS Pathog 6 e1000913
20. SakumaTNodaTUrataSKawaokaYYasudaJ 2009 Inhibition of Lassa and Marburg virus production by tetherin. J Virol 83 2382 2385
21. KaletskyRLFrancicaJRAgrawal-GamseCBatesP 2009 Tetherin-mediated restriction of filovirus budding is antagonized by the Ebola glycoprotein. Proc Natl Acad Sci U S A 106 2886 2891
22. JouvenetNNeilSJDZhadinaMZangTKratovacZ 2009 Broad-spectrum inhibition of Retroviral and Filoviral particle release by tetherin. J Virol 83 1837 1844
23. ZhangFWilsonSJLandfordWCVirgenBGregoryD 2009 Nef proteins from simian immunodeficiency viruses are tetherin antagonists. Cell Host Microbe 6 54 67
24. ArnaudFBlackSMurphyLGriffithsDNeilSJ 2010 Interplay between Ovine bone marrow stromal cell antigen 2 (BST2)/Tetherin and endogenous retroviruses. J Virol 84 4415 4425
25. KupzigSKorolchukVRollasonRSugdenAWildeA 2003 Bst-2/HM1.24 is a raft-associated apical membrane protein with an unusual topology. Traffic 4 694 709
26. RollasonRKorolchukVHamiltonCSchuPBantingG 2007 Clathrin-mediated endocytosis of a lipid-raftassociated protein is mediated through a dual tyrosine motif. J Cell Sci 120 3850 3858
27. HinzAMiguetNNatrajanGUsamiYYamanakaH 2010 Structural Basis of HIV-1 Tethering to Membranes by the BST-2/Tetherin Ectodomain. Cell Host Microbe 7 1 10
28. BieniaszPD 2009 The cell biology of HIV-1 virion genesis. Cell Host Microbe 5 550 558
29. KalejtaRF 2008 Tegument proteins of human cytomegalovirus. Microbiol Mol Biol Rev 72 249 265
30. DeFilippisVRRobinsonBKeckTMHansenSGNelsonJA 2006 Interferon regulatory factor 3 is necessary for induction of antiviral genes during human cytomegalovirus infection. J Virol 80 1032 1037
31. MillerDMRahillBMBossJMLairmoreMDDurbinJE 1998 Human cytomegalovirus inhibits major histocompatibility complex class II expression by disruption of the Jak/Stat pathway. J Exp Med 187 675 683
32. NavarroLMowenKRodemsSWeaverBReichN 1998 Cytomegalovirus activates interferon immediate-early response gene expression and an interferon regulatory factor 3-containing interferon-stimulated response element-binding complex. Mol Cell Biol 18 3796 3802
33. SmithMSBentzGLAlexanderJSYurochkoAD 2004 Human cytomegalovirus induces monocyte differentiation and migration as a strategy for dissemination and persistence. J Virol 78 4444 4453
34. Soderberg-NauclerCFishKNNelsonJA 1997 Reactivation of latent human cytomegalovirus by allogeneic stimulation of blood cells from healthy donors. Cell 91 119 126
35. IbanezCESchrierRGhazalPWileyCNelsonJA 1991 Human cytomegalovirus productively infects primary differentiated macrophages. J Virol 65 6581 6588
36. TurtinenLWSeufzerBJ 1994 Selective permissiveness of TPA differentiated THP-1 myelomonocytic cells for human cytomegalovirus strains AD169 and Towne. Microb Pathog 16 373 378
37. GernaGPercivalleESarasiniABaldantiFCampaniniG 2003 Rescue of human cytomegalovirus strain AD169 tropism for both leukocytes and human endothelial cells. J Gen Virol 84 1431 1436
38. VarnumSMStreblowDNMonroeMESmithPAuberryKJ 2004 Identification of proteins in human cytomegalovirus(HCMV) particles: the HCMV proteome. J Virol 78 10960 10966
39. DeFilippisVRAlvaradoDSaliTRothenburgSFrühK 2010 Human Cytomegalovirus Induces the Interferon Response via the DNA Sensor ZBP1. J Virol 84 585 598
40. Perez-CaballeroDZangTEbrahimiAMcNattMWGregoryDA 2009 Tetherin Inhibits HIV-1 release by directly tethering virions to cells. Cell 139 499 511
41. WillcoxBEThomasLMChapmanTLHeikemaAPWestAP 2002 Crystal structure of LIR-2 (ILT4) at 1.8 Å: differences from LIR-1 (ILT2) in regions implicated in the binding of the Human Cytomegalovirus class I MHC homolog UL18. BMC Struct Biol 2 6
42. OzakiSKosakaMWakatsukiSAbeMKoishiharaY 1997 Immunotherapy of Multiple Myeloma With a Monoclonal Antibody Directed Against a Plasma Cell-Specific Antigen, HM1.24. Blood 90 3179 3186
43. MichaelisMDoerrHWCinatlJ 2009 The story of human cytomegalovirus and cancer: increasing evidence and open questions. Neoplasia 11 1 9
44. BresnahanWAHultmanGEShenkT 2000 Replication of wild-type and mutant human cytomegalovirus in life-extended human diploid fibroblasts. J Virol 74 10816 10818
45. KalejtaRF 2003 Human cytomegalovirus pp71 stimulates cell cycle progression by inducing the proteasome-dependant degradation of the retinoblastoma family of tumor suppressors. Mol Cell Biol 23 1885 1895
Štítky
Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
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