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  • Original Paper
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The HPV16 E5 oncogene inhibits endocytic trafficking

Abstract

The small hydrophobic E5 protein of Human Papillomavirus type 16 (HPV16) binds to the 16-kDa subunit of the V-H+-ATPase. This binding has been suggested to interfere with acidification of late endocytic structures. We here used video microscopy, ratio imaging and confocal microscopy of living C127 fibroblasts to study the effects of E5. Various endocytic markers including the pH-sensitive probe DM-NERF coupled to dextran, TransFluoSpheres and TRITC-concanavalin A, were applied. In E5-transfected cells, none of these markers colocalized with the membrane permeable probe LysoTracker Red, which accumulates in acidic, late endocytic structures, or with a green fluorescent version of the small GTPase Rab7 labeling late endocytic structures. Importantly, however, late endocytic structures accumulating LysoTracker were still present in the E5-transfected cells. It is therefore concluded that HPV16 E5 perturbs trafficking from early to late endocytic structures rather than acidification.

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References

  • Barois N, Forquet F and Davoust J. . 1998 J. Cell. Sci. 111: 1791–1800.

  • Bar-Ziv R, Tlusty T, Moses E, Safran SA and Bershadsky A. . 1999 Proc. Natl. Acad. Sci. USA 96: 10140–10145.

  • Bergman P, Ustav M, Sedman J, Moreno-Lopez J, Vennstrom B and Pettersson U. . 1988 Oncogene 2: 453–459.

  • Bowman EJ, Siebers A and Altendorf K. . 1988 Proc. Natl. Acad. Sci. USA 85: 7972–7976.

  • Bubb V, McCance DJ and Schlegel R. . 1988 Virology 163: 243–246.

  • Bucci C, Thomsen P, Nicoziani P, McCarthy J and van Deurs B. . 2000 Mol. Biol. Cell 11: 467–480.

  • Conrad M, Bubb VJ and Schlegel R. . 1993 J. Virol. 67: 6170–6178.

  • Crider BP, Xie XS and Stone DK. . 1994 J. Biol. Chem. 269: 17379–17381.

  • Critchley DR, Holt MR, Barry ST, Priddle H, Hemmings L and Norman J. . 1999 Biochem. Soc. Symp. 65: 79–99.

  • Crusius K, Kaszkin M, Kinzel V and Alonso A. . 1999 Oncogene 18: 6714–6718.

  • DePina AS and Langford GM. . 1999 Microsc. Res. Tech. 47: 93–106.

  • Drose S and Altendorf K. . 1997 J. Exp. Biol. 200: 1–8.

  • Drose S, Bindseil KU, Bowman EJ, Siebers A, Zeeck A and Altendorf K. . 1993 Biochemistry 32: 3902–3906.

  • Evans LL, Lee AJ, Bridgman PC and Mooseker MS. . 1998 J. Cell. Sci. 111: 2055–2066.

  • Fagotto F and Maxfield FR. . 1994 J. Cell. Sci. 107: 3325–3337.

  • Giancotti FG. . 2000 Nat. Cell. Biol. 2: E13–E14.

  • Goldstein DJ, Finbow ME, Andresson T, McLean P, Smith K, Bubb V and Schlegel R. . 1991 Nature 352: 347–349.

  • Halbert CL and Galloway DA. . 1988 J. Virol. 62: 1071–1075.

  • Harada M, Shakado S, Sakisaka S, Tamaki S, Ohishi M, Sasatomi K, Koga H, Sata M and Tanikawa K. . 1997 Liver 17: 244–250.

  • Huang JD, Brady ST, Richards BW, Stenolen D, Resau JH, Copeland NG and Jenkins NA. . 1999 Nature 397: 267–270.

  • Ishiguro H, Steward MC, Wilson RW and Case RM. . 1996 J. Physiol. (Lond.) 495: 179–191.

  • Janmey PA and Chaponnier C. . 1995 Curr. Opin. Cell. Biol. 7: 111–117.

  • Johnson CK, Stanley M and Norrild B. . 1995 Intervirology 38: 339–345.

  • Lee RJ, Wang S and Low PS. . 1996 Biochim. Biophys. Acta 1312: 237–242.

  • Lin HJ, Szmacinski H and Lakowicz JR. . 1999 Anal. Biochem. 269: 162–167.

  • Lyass LA, Bershadsky AD, Gelfand VI, Serpinskaya AS, Stavrovskaya AA, Vasiliev JM and Gelfand IM. . 1984 Proc. Natl. Acad. Sci. USA 81: 3098–3102.

  • Magez S, Geuskens M, Beschin A, del Favero H, Verschueren H, Lucas R, Pays E and de Baetselier P. . 1997 J. Cell. Biol. 137: 715–727.

  • Manabe T, Yoshimori T, Henomatsu N and Tashiro Y. . 1993 J. Cell. Physiol. 157: 445–452.

  • McCance DJ. . 1994 Infect. Dis. Clin. North Am. 8: 751–767.

  • McCance DJ, Campion MJ, Clarkson PK, Chesters PM, Jenkins D and Singer A. . 1985 Br. J. Obstet. Gynaecol. 92: 1101–1105.

  • Mizejewski GJ. . 1999 Proc. Soc. Exp. Biol. Med. 222: 124–138.

  • Morgenstern JP and Land H. . 1990 Nucleic Acids Res. 18: 1068.

  • O'Neill GM, Fashena SJ and Golemis EA. . 2000 Trends Cell. Biol. 10: 111–119.

  • Raposo G, Cordonnier MN, Tenza D, Menichi B, Durrbach A, Louvard D and Coudrier E. . 1999 Mol. Biol. Cell 10: 1477–1494.

  • Rathman M, Sjaastad MD and Falkow S. . 1996 Infect. Immun. 64: 2765–2773.

  • Schaller MD, Otey CA, Hildebrand JD and Parsons JT. . 1995 J. Cell Biol. 130: 1181–1187.

  • Schapiro F, Sparkowski J, Adducci A, Suprynowicz F, Schlegel R and Grinstein S. . 2000 J. Cell Biol. 148: 305–316.

  • Skinner MA and Wildeman AG. . 1999 J. Biol. Chem. 274: 23119–23127.

  • Sparkowski J, Anders J and Schlegel R. . 1995 EMBO J. 14: 3055–3063.

  • Stanley MA, Browne HM, Appleby M and Minson AC. . 1989 Int. J. Cancer 43: 672–676.

  • Straight SW, Herman B and McCance DJ. . 1995 J. Virol. 69: 3185–3192.

  • Straight SW, Hinkle PM, Jewers RJ and McCance DJ. . 1993 J. Virol. 67: 4521–4532.

  • Syrjanen SM and Syrjanen KJ. . 1999 Ann. Med. 31: 175–187.

  • Taunton J, Rowning BA, Coughlin ML, Wu M, Moon RT, Mitchison TJ and Larabell CA. . 2000 J. Cell. Biol. 148: 519–530.

  • Thomsen P, Rudenko O, Berezin V and Norrild B. . 1999 Biochim. Biophys. Acta 1452: 285–295.

  • Tong X and Howley PM. . 1997 Proc. Natl. Acad. Sci. USA 94: 4412–4417.

  • Valle GF and Banks L. . 1995 J. Gen. Virol. 76: 1239–1245.

  • van Deurs B, Holm PK, Kayser L and Sandvig K. . 1995 Eur. J. Cell. Biol. 66: 309–323.

  • Venuti A, Salani D, Poggiali F, Manni V and Bagnato A. . 1998 Virology 248: 1–5.

  • Vousden K. . 1993 FASEB J. 7: 872–879.

  • Wubbolts R, Fernandez-Borja M, Ooomen L, Verwoerd D, Janssen H, Calafat J, Tulp A, Dusseljee S and Neefjes J. . 1996 J. Cell Biol. 135: 611–622.

  • zur Hausen H. . 1999 Proc. Assoc. Am. Phys. 111: 581–587.

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Acknowledgements

We thank M Stanley for supplying W12 cells. This work was supported by grants from the Danish Cancer Society, the Danish Medical Research Council, and the Novo Nordisk Foundation, the biotechnology program, Civil ingeniør Bent Bøgh og hustru Inge Bøgh's fond, Dagmar Marshalls foundation and Lykfeldts foundation. P Thomsen was working in the van Deurs laboratory with the support of a Ph.D. grant from the Faculty of Health Sciences, University of Copenhagen.

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Thomsen, P., van Deurs, B., Norrild, B. et al. The HPV16 E5 oncogene inhibits endocytic trafficking. Oncogene 19, 6023–6032 (2000). https://doi.org/10.1038/sj.onc.1204010

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