PMID:20686024

Citation	Suprynowicz, FA, Krawczyk, E, Hebert, JD, Sudarshan, SR, Simic, V, Kamonjoh, CM and Schlegel, R (2010) The human papillomavirus type 16 E5 oncoprotein inhibits epidermal growth factor trafficking independently of endosome acidification. J. Virol. 84:10619-29
Abstract	The human papillomavirus type 16 E5 oncoprotein (16E5) enhances acute, ligand-dependent activation of the epidermal growth factor receptor (EGFR) and concomitantly alkalinizes endosomes, presumably by binding to the 16-kDa "c" subunit of the V-ATPase proton pump (16K) and inhibiting V-ATPase function. However, the relationship between 16K binding, endosome alkalinization, and altered EGFR signaling remains unclear. Using an antibody that we generated against 16K, we found that 16E5 associated with only a small fraction of endogenous 16K in keratinocytes, suggesting that it was unlikely that E5 could significantly affect V-ATPase function by direct inhibition. Nevertheless, E5 inhibited the acidification of endosomes, as determined by a new assay using a biologically active, pH-sensitive fluorescent EGF conjugate. Since we also found that 16E5 did not alter cell surface EGF binding, the number of EGFRs on the cell surface, or the endocytosis of prebound EGF, we postulated that it might be blocking the fusion of early endosomes with acidified vesicles. Our studies with pH-sensitive and -insensitive fluorescent EGF conjugates and fluorescent dextran confirmed that E5 prevented endosome maturation (acidification and enlargement) by inhibiting endosome fusion. The E5-dependent defect in vesicle fusion was not due to detectable disruption of actin, tubulin, vimentin, or cytokeratin filaments, suggesting that membrane fusion was being directly affected rather than vesicle transport. Perhaps most importantly, while bafilomycin A(1) (like E5) binds to 16K and inhibits endosome acidification, it did not mimic the ability of E5 to inhibit endosome enlargement or the trafficking of EGF. Thus, 16E5 alters EGF endocytic trafficking via a pH-independent inhibition of vesicle fusion.
Links	PubMed PMC2950579 Online version:10.1128/JVI.00831-10
Keywords	Animals; Biological Transport, Active; COS Cells; Cells, Cultured; Cercopithecus aethiops; Endosomes/physiology; Endosomes/virology; Epidermal Growth Factor/physiology; Host-Pathogen Interactions/genetics; Host-Pathogen Interactions/physiology; Human papillomavirus 16/genetics; Human papillomavirus 16/pathogenicity; Human papillomavirus 16/physiology; Humans; Hydrogen-Ion Concentration; Oncogene Proteins, Viral/genetics; Oncogene Proteins, Viral/physiology; Proton-Translocating ATPases/antagonists & inhibitors; Receptor, Epidermal Growth Factor/physiology; Virus Internalization
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HPV16:VE5		GO:0019048: modulation by virus of host morphology or physiology	ECO:0000314:		P		Figure 8 depicts the inhibition of endosome vesicle fusion by HP16 E5 protein	complete CACAO 8856
HPV16:VE5	involved_in	GO:0019048: modulation by virus of host morphology or physiology	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete

References

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