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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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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DOI: https://doi.org/10.1038/sj.onc.1204010
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