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Human parainfluenza virus type 2 V protein inhibits induction of tetherin

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Abstract

Tetherin is an anti-viral factor that restricts viral budding through tethering virions to the cell surface. The human parainfluenza virus type 2 (hPIV-2) V protein decreases cell surface tetherin in HeLa cells, which constitutively express endogenous tetherin. However, the role of the hPIV-2 V protein in tetherin induction remains unclear. Here, we examined whether hPIV-2 infection itself induces tetherin in HEK293 cells that have no basal expression of tetherin. Unlike influenza A virus (IAV) infection, hPIV-2 infection induced neither tetherin mRNA nor protein expression. In contrast, robust tetherin induction was observed by infection of rPIV-2s carrying V mutants, in which either three Trp residues (W178H/W182E/W192A) or Cys residues (C209/211/214A) that are important for decreasing cell surface tetherin are mutated. hPIV-2 infection also inhibited the induction of tetherin expression by IFN-α and IAV infection. Furthermore, hPIV-2 V protein but not P and VW178H/W182E/W192A suppressed tetherin induction. Our data collectively suggest that the hPIV-2 V protein inhibits tetherin expression induced by several external stimuli.

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References

  1. Ishikawa J, Kaisho T, Tomizawa H, Lee BO, Kobune Y, Inazawa J, Oritani K, Itoh M, Ochi T, Ishihara K, Hirano T (1995) Molecular cloning and chromosomal mapping of a bone marrow stromal cell surface gene, BST2, that may be involved in pre-B-cell growth. Genomics 26:527–534. doi:10.1016/0888-7543(95)80171-H

    Article  CAS  PubMed  Google Scholar 

  2. Neil SJ, Zang T, Bieniasz PD (2008) Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu. Nature 451:425–430. doi:10.1038/nature06553

    Article  CAS  PubMed  Google Scholar 

  3. Van Damme N, Goff D, Katsura C, Jorgenson RL, Mitchell R, Johnson MC, Stephens EB, Guatelli J (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. doi:10.1016/j.chom.2008.03.001

    Article  PubMed  PubMed Central  Google Scholar 

  4. Kaletsky RL, Francica JR, Agrawal-Gamse C, Bates P (2009) Tetherin-mediated restriction of filovirus budding is antagonized by the Ebola glycoprotein. Proc Natl Acad Sci USA 106:2886–2891. doi:10.1073/pnas.0811014106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Watanabe R, Leser GP, Lamb RA (2011) Influenza virus is not restricted by tetherin whereas influenza VLP production is restricted by tetherin. Virology 417:50–56. doi:10.1016/j.virol.2011.05.006

    Article  CAS  PubMed  Google Scholar 

  6. Yondola MA, Fernandes F, Belicha-Villanueva A, Uccelini M, Gao Q, Carter C, Palese P (2011) Budding capability of the influenza virus neuraminidase can be modulated by tetherin. J Virol 85:2480–2491. doi:10.1128/JVI.02188-10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Mangeat B, Cavagliotti L, Lehmann M, Gers-Huber G, Kaur I, Thomas Y, Kaiser L, Piguet V (2012) Influenza virus partially counteracts restriction imposed by tetherin/BST-2. J Biol Chem 287:22015–22029. doi:10.1074/jbc.M111.319996

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Bampi C, Rasga L, Roux L (2013) Antagonism to human BST-2/tetherin by Sendai virus glycoproteins. J Gen Virol 94:1211–1219. doi:10.1099/vir.0.051771-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Ohta K, Goto H, Yumine N, Nishio M (2016) Human parainfluenza virus type 2 V protein inhibits and antagonizes tetherin. J Gen Virol 97:561–570. doi:10.1099/jgv.0.000373

    Article  CAS  PubMed  Google Scholar 

  10. Sarojini S, Theofanis T, Reiss CS (2011) Interferon-induced tetherin restricts vesicular stomatitis virus release in neurons. DNA Cell Biol 30:965–974. doi:10.1089/dna.2011.1384

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Winkler M, Bertram S, Gnirß K, Nehlmeier I, Gawanbacht A, Kirchhoff F, Ehrhardt C, Ludwig S, Kiene M, Moldenhauer AS, Goedecke U, Karsten CB, Kühl A, Pöhlmann S (2012) Influenza A virus does not encode a tetherin antagonist with Vpu-like activity and induces IFN-dependent tetherin expression in infected cells. PLoS One 7:e43337. doi:10.1371/journal.pone.0043337

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Jones PH, Okeoma CM (2013) Phosphatidylinositol 3-kinase is involved in Toll-like receptor 4-mediated BST-2/tetherin regulation. Cell Signal 25:2752–2761. doi:10.1016/j.cellsig.2013.08.042

    Article  CAS  PubMed  Google Scholar 

  13. Ohta K, Goto H, Matsumoto Y, Yumine N, Tsurudome M, Nishio M (2016) Graf1 controls the growth of human parainfluenza virus type 2 through inactivation of RhoA signaling. J Virol 90:9394–9405. doi:10.1128/JVI.01471-16

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Nishio M, Tsurudome M, Ito M, Garcin D, Kolakofsky D, Ito Y (2005) Identification of paramyxovirus V protein residues essential for STAT protein degradation and promotion of virus replication. J Virol 79:8591–8601. doi:10.1128/JVI.79.13.8591-8601.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Goto H, Ihira H, Morishita K, Tsuchiya M, Ohta K, Yumine N, Tsurudome M, Nishio M (2016) Enhanced growth of influenza A virus by coinfection with human parainfluenza virus type 2. Med Microbiol Immunol 205:209–218. doi:10.1007/s00430-015-0441-y

    Article  CAS  PubMed  Google Scholar 

  16. Nishio M, Tsurudome M, Ito M, Watanabe N, Kawano M, Komada H, Ito Y (1997) Human parainfluenza virus type 2 phosphoprotein: mapping of monoclonal antibody epitopes and location of the multimerization domain. J Gen Virol 78:1303–1308. doi:10.1099/0022-1317-78-6-1303

    Article  CAS  PubMed  Google Scholar 

  17. Nishio M, Tsurudome M, Ito M, Kawano M, Kusagawa S, Komada H, Ito Y (1999) Mapping of domains on the human parainfluenza virus type 2 nucleocapsid protein (NP) required for NP-phosphoprotein or NP-NP interaction. J Gen Virol 80:2017–2022. doi:10.1099/0022-1317-80-8-2017

    Article  CAS  PubMed  Google Scholar 

  18. Miyagi E, Andrew AJ, Kao S, Strebel K (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. doi:10.1073/pnas.0813223106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Nishio M, Garcin D, Simonet V, Kolakofsky D (2002) The carboxyl segment of the mumps virus V protein associates with Stat proteins in vitro via a tryptophan-rich motif. Virology 300:92–99. doi:10.1006/viro.2002.1509

    Article  CAS  PubMed  Google Scholar 

  20. Andrejeva J, Childs KS, Young DF, Carlos TS, Stock N, Goodbourn S, Randall RE (2004) The V proteins of paramyxoviruses bind the IFN-inducible RNA helicase, mda-5, and inhibit its activation of the IFN-b promoter. Proc Natl Acad Sci USA 101:17264–17269. doi:10.1073/pnas.0407639101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Kitagawa Y, Yamaguchi M, Zhou M, Nishio M, Itoh M, Gotoh B (2013) Human parainfluenza virus type 2 V protein inhibits TRAF6-mediated ubiquitination of IRF7 to prevent TLR7- and TLR9-dependent interferon induction. J Virol 87:7966–7976. doi:10.1128/JVI.03525-12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Nishio M, Tsurudome M, Ito M, Kawano M, Komada H, Ito Y (2001) High resistance of human parainfluenza type 2 virus protein-expressing cells to the antiviral and anti-cell proliferative activities of alpha/beta interferons: cysteine-rich V-specific domain is required for high resistance to the interferons. J Virol 75:9165–9176. doi:10.1128/JVI.75.19.9165-9176.2001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Bego MG, Mercier J, Cohen EA (2012) Virus-activated interferon regulatory factor 7 upregulates expression of the interferon-regulated BST2 gene independently of interferon signaling. J Virol 86:3513–3527. doi:10.1128/JVI.06971-11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Kitagawa Y, Yamaguchi M, Zhou M, Komatsu T, Nishio M, Sugiyama T, Takeuchi K, Itoh M, Gotoh B (2011) A tryptophan-rich motif in the human parainfluenza virus type 2 V protein is critical for the blockade of toll-like receptor 7 (TLR7)- and TLR9-dependent signaling. J Virol 85:4606–4611. doi:10.1128/JVI.02012-10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Cocka LJ, Bates P (2012) Identification of alternatively translated Tetherin isoforms with differing antiviral and signaling activities. PLoS Pathog 8:e1002931. doi:10.1371/journal.ppat.1002931

    Article  PubMed  PubMed Central  Google Scholar 

  26. Galão RP, Le Tortorec A, Pickering S, Kueck T, Neil SJ (2012) Innate sensing of HIV-1 assembly by tetherin induces NFκB-dependent proinflammatory responses. Cell Host Microbe 12:633–644. doi:10.1016/j.chom.2012.10.007

    Article  PubMed  PubMed Central  Google Scholar 

  27. Tokarev A, Suarez M, Kwan W, Fitzpatrick K, Singh R, Guatelli J (2013) Stimulation of NF-κB activity by the HIV restriction factor BST2. J Virol 87:2046–2057. doi:10.1128/JVI.02272-12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Hotter D, Sauter D, Kirchhoff F (2013) Emerging role of the host restriction factor tetherin in viral immune sensing. J Mol Biol 425:4956–4964. doi:10.1016/j.jmb.2013.09.029

    Article  CAS  PubMed  Google Scholar 

  29. Ohtomo T, Sugamata Y, Ozaki Y, Ono K, Yoshimura Y, Kawai S, Koishihara Y, Ozaki S, Kosaka M, Hirano T, Tsuchiya M (1999) Molecular cloning and characterization of a surface antigen preferentially overexpressed on multiple myeloma cells. Biochem Biophys Res Commun 258:583–591. doi:10.1006/bbrc.1999.0683

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank Drs. Klaus Strebel and Amy Andrew for anti-Bst2 via the NIH AIDS Research and Reference Reagent Program.

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Authors and Affiliations

  1. Department of Microbiology, School of Medicine, Wakayama Medical University, 811-1, Kimiidera, Wakayama, 641-8509, Japan

    Keisuke Ohta, Yusuke Matsumoto, Natsuko Yumine & Machiko Nishio

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  1. Keisuke Ohta
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  2. Yusuke Matsumoto
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  3. Natsuko Yumine
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  4. Machiko Nishio
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Correspondence to Machiko Nishio.

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Ohta, K., Matsumoto, Y., Yumine, N. et al. Human parainfluenza virus type 2 V protein inhibits induction of tetherin. Med Microbiol Immunol 206, 311–318 (2017). https://doi.org/10.1007/s00430-017-0508-z

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  • DOI: https://doi.org/10.1007/s00430-017-0508-z

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