Retrovirology | |
Bone marrow stromal cell antigen 2 (BST-2) restricts mouse mammary tumor virus (MMTV) replication in vivo | |
Chioma M Okeoma1  Richard J Roller1  Martina Maric1  Harshini V Mehta1  Philip H Jones1  | |
[1] Department of Microbiology, University of Iowa, Carver College of Medicine, Iowa City, IA, USA | |
关键词: TEM; SEM; In vivo; MMTV; Interferon alpha; Tetherin; BST-2; | |
Others : 1209350 DOI : 10.1186/1742-4690-9-10 |
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received in 2011-10-20, accepted in 2012-01-27, 发布年份 2012 | |
【 摘 要 】
Background
Bone marrow stromal cell antigen 2 (BST-2) is a cellular factor that restricts the egress of viruses such as human immunodeficiency virus (HIV-1) from the surface of infected cells, preventing infection of new cells. BST-2 is variably expressed in most cell types, and its expression is enhanced by cytokines such as type I interferon alpha (IFN-α). In this present study, we used the beta-retrovirus, mouse mammary tumor virus (MMTV) as a model to examine the role of mouse BST-2 in host infection in vivo.
Results
By using RNA interference, we show that loss of BST-2 enhances MMTV replication in cultured mammary tumor cells and in vivo. In cultured cells, BST-2 inhibits virus accumulation in the culture medium, and co-localizes at the cell surface with virus structural proteins. Furthermore, both scanning electron micrograph (SEM) and transmission electron micrograph (TEM) show that MMTV accumulates on the surface of IFNα-stimulated cells.
Conclusions
Our data provide evidence that BST-2 restricts MMTV release from naturally infected cells and that BST-2 is an antiviral factor in vivo.
【 授权许可】
2012 Jones et al; licensee BioMed Central Ltd.
【 预 览 】
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【 参考文献 】
- [1]Neil SJ, Zang T, Bieniasz PD: Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu. Nature 2008, 451:425-30.
- [2]Goffinet C, Schmidt S, Kern C, Oberbremer L, Keppler OT: 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 2010, 84:11374-84.
- [3]Jouvenet N, Neil SJ, Zhadina M, Zang T, Kratovac Z, Lee Y, McNatt M, Hatziioannou T, Bieniasz PD: Broad-spectrum inhibition of retroviral and filoviral particle release by tetherin. J Virol 2009, 83:1837-44.
- [4]Kaletsky RL, Francica JR, Agrawal-Gamse C, Bates P: Tetherin-mediated restriction of filovirus budding is antagonized by the Ebola glycoprotein. Proc Natl Acad Sci USA 2009, 106:2886-91.
- [5]Lopez LA, Yang SJ, Hauser H, Exline CM, Haworth KG, Oldenburg J, Cannon PM: Ebola virus glycoprotein counteracts BST-2/Tetherin restriction in a sequence-independent manner that does not require tetherin surface removal. J Virol 2010, 84:7243-55.
- [6]Perez-Caballero D, Zang T, Ebrahimi A, McNatt MW, Gregory DA, Johnson MC, Bieniasz PD: Tetherin inhibits HIV-1 release by directly tethering virions to cells. Cell 2009, 139:499-511.
- [7]Habermann A, Krijnse-Locker J, Oberwinkler H, Eckhardt M, Homann S, Andrew A, Strebel K, Krausslich HG: CD317/tetherin is enriched in the HIV-1 envelope and downregulated from the plasma membrane upon virus infection. J Virol 2010, 84:4646-58.
- [8]Hammonds J, Wang JJ, Yi H, Spearman P: Immunoelectron microscopic evidence for Tetherin/BST2 as the physical bridge between HIV-1 virions and the plasma membrane. PLoS Pathog 2010, 6:e1000749.
- [9]Fitzpatrick K, Skasko M, Deerinck TJ, Crum J, Ellisman MH, Guatelli J: Direct restriction of virus release and incorporation of the interferon-induced protein BST-2 into HIV-1 particles. PLoS Pathog 2010, 6:e1000701.
- [10]Le Tortorec A, Neil SJ: Antagonism to and intracellular sequestration of human tetherin by the human immunodeficiency virus type 2 envelope glycoprotein. J Virol 2009, 83:11966-78.
- [11]Dube M, Roy BB, Guiot-Guillain P, Mercier J, Binette J, Leung G, Cohen EA: Suppression of Tetherin-restricting activity upon human immunodeficiency virus type 1 particle release correlates with localization of Vpu in the trans-Golgi network. J Virol 2009, 83:4574-90.
- [12]Goffinet C, Homann S, Ambiel I, Tibroni N, Rupp D, Keppler OT, Fackler OT: Antagonism of CD317 restriction of human immunodeficiency virus type 1 (HIV-1) particle release and depletion of CD317 are separable activities of HIV-1 Vpu. J Virol 2010, 84:4089-94.
- [13]Hauser H, Lopez LA, Yang SJ, Oldenburg JE, Exline CM, Guatelli JC, Cannon PM: HIV-1 Vpu and HIV-2 Env counteract BST-2/tetherin by sequestration in a perinuclear compartment. Retrovirology 2010, 7:51. BioMed Central Full Text
- [14]Pardieu C, Vigan R, Wilson SJ, Calvi A, Zang T, Bieniasz P, Kellam P, Towers GJ, Neil SJ: The RING-CH ligase K5 antagonizes restriction of KSHV and HIV-1 particle release by mediating ubiquitin-dependent endosomal degradation of tetherin. PLoS Pathog 2010, 6:e1000843.
- [15]Burzyn D, Rassa JC, Kim D, Nepomnaschy I, Ross SR, Piazzon I: Toll-like receptor 4-dependent activation of dendritic cells by a retrovirus. J Virol 2004, 78:576-84.
- [16]Beutner U, Kraus E, Kitamura D, Rajewsky K, Huber BT: B cells are essential for murine mammary tumor virus transmission, but not for presentation of endogenous superantigens. J Exp Med 1994, 179:1457-66.
- [17]Martin P, Ruiz SR, del Hoyo GM, Anjuere F, Vargas HH, Lopez-Bravo M, Ardavin C: Dramatic increase in lymph node dendritic cell number during infection by the mouse mammary tumor virus occurs by a CD62L-dependent blood-borne DC recruitment. Blood 2002, 99:1282-8.
- [18]Courreges MC, Burzyn D, Nepomnaschy I, Piazzon I, Ross SR: Critical role of dendritic cells in mouse mammary tumor virus in vivo infection. J Virol 2007, 81:3769-77.
- [19]Dzuris JL, Golovkina TV, Ross SR: Both T and B cells shed infectious mouse mammary tumor virus. J Virol 1997, 71:6044-8.
- [20]Golovkina TV, Dudley JP, Ross SR: B and T cells are required for mouse mammary tumor virus spread within the mammary gland. J Immunol 1998, 161:2375-82.
- [21]Okeoma CM, Huegel AL, Lingappa J, Feldman MD, Ross SR: APOBEC3 proteins made in mammary epithelial cells can be packaged into retroviruses and restrict transmission of milk-borne virions. Cell Host Microbe 2010, 8:534-43.
- [22]Yoo H, Park SH, Ye SK, Kim M: IFN-gamma-induced BST2 mediates monocyte adhesion to human endothelial cells. Cell Immunol 2011, 267:23-9.
- [23]Zhang F, Wilson SJ, Landford WC, Virgen B, Gregory D, Johnson MC, Munch J, Kirchhoff F, Bieniasz PD, Hatziioannou T: Nef proteins from simian immunodeficiency viruses are tetherin antagonists. Cell Host Microbe 2009, 6:54-67.
- [24]Jolly C, Booth NJ, Neil SJ: Cell-cell spread of human immunodeficiency virus type 1 overcomes tetherin/BST-2-mediated restriction in T cells. J Virol 2010, 84:12185-99.
- [25]Serra-Moreno R, Jia B, Breed M, Alvarez X, Evans DT: Compensatory changes in the cytoplasmic tail of gp41 confer resistance to tetherin/BST-2 in a pathogenic nef-deleted SIV. Cell Host Microbe 2011, 9:46-57.
- [26]Indik S, Gunzburg WH, Salmons B, Rouault F: Mouse mammary tumor virus infects human cells. Cancer Res 2005, 65:6651-9.
- [27]Gonda MA, Arthur LO, Zeve VH, Fine DL, Nagashima K: Surface localization of virus production on a glucocorticoid-stimulated oncornavirus-producing mouse mammary tumor cell line by scanning electron microscopy. Cancer Res 1976, 36:1084-93.
- [28]Bittner JJ: SOME POSSIBLE EFFECTS OF NURSING ON THE MAMMARY GLAND TUMOR INCIDENCE IN MICE. Science 1936, 84:162.
- [29]Shackleford GM, Varmus HE: Construction of a clonable, infectious, and tumorigenic mouse mammary tumor virus provirus and a derivative genetic vector. Proc Natl Acad Sci USA 1988, 85:9655-9.
- [30]Miesfeld R, Rusconi S, Godowski PJ, Maler BA, Okret S, Wikstrom AC, Gustafsson JA, Yamamoto KR: Genetic complementation of a glucocorticoid receptor deficiency by expression of cloned receptor cDNA. Cell 1986, 46:389-99.
- [31]Zhang Y, Rassa JC, deObaldia ME, Albritton LM, Ross SR: Identification of the receptor binding domain of the mouse mammary tumor virus envelope protein. J Virol 2003, 77:10468-78.
- [32]Okeoma CM, Lovsin N, Peterlin BM, Ross SR: APOBEC3 inhibits mouse mammary tumour virus replication in vivo. Nature 2007, 445:927-30.
- [33]Okeoma CM, Shen M, Ross SR: A novel block to mouse mammary tumor virus infection of lymphocytes in B10.BR mice. J Virol 2008, 82:1314-22.
- [34]Schliemann C, Roesli C, Kamada H, Borgia B, Fugmann T, Klapper W, Neri D: In vivo biotinylation of the vasculature in B-cell lymphoma identifies BST-2 as a target for antibody-based therapy. Blood 2010, 115:736-44.
- [35]Parks WP, Ransom JC, Young HA, Scolnick EM: Mammary tumor virus induction by glucocorticoids Characterization of specific transcriptional regulation. J Biol Chem 1975, 250:3330-6.