The cellular endosomal protein stannin inhibits intracellular trafficking of human papillomavirus during virus entry

Alex Lipovsky, Asu Erden, Eriko Kanaya, Wei Zhang, Mac Crite, Clinton Bradfield, John MacMicking, Daniel DiMaio, John W. Schoggins, Akiko Iwasaki

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Human papillomaviruses (HPVs) are the most common sexually transmitted viruses and one of the most important infectious causes of cancers worldwide. While prophylactic vaccines are effective against certain strains of HPV, established infections still cause deadly cancers in both men and women. HPV traffics to the nucleus via the retrograde transport pathway, but the mechanism of intracellular transport of non-enveloped viruses such as HPV is incompletely understood. Using an overexpression screen, we identify several genes that control HPV16 entry. We focused on the mechanism by which one of the screen hits, stannin, blocks HPV16 infection. Stannin has not been previously implicated in virus entry. Overexpression of stannin specifically inhibits infection by several HPV types, but not other viruses tested. Stannin is constitutively expressed in human keratinocytes, and its basal levels limit entry by HPV16. Stannin is localized to the endolysosomal compartment and does not affect HPV16 binding to cells, virus uptake, or virus uncoating, but inhibits the entry of HPV into the trans-Golgi network (TGN) and stimulates HPV degradation. We further show that stannin interacts with L1 major capsid protein and impairs the interaction of the L2 minor capsid protein with retromer, which is required for virus trafficking to the TGN. Our findings shed light on a novel cellular protein that interferes with HPV entry and highlight the role of retrograde transport in HPV entry.

Original languageEnglish (US)
Article number000954
Pages (from-to)2821-2836
Number of pages16
JournalJournal of General Virology
Volume98
Issue number11
DOIs
Publication statusPublished - Nov 1 2017

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Keywords

  • Intracellular trafficking
  • Retrograde transport
  • Retromer
  • Viral entry

ASJC Scopus subject areas

  • Virology

Cite this

Lipovsky, A., Erden, A., Kanaya, E., Zhang, W., Crite, M., Bradfield, C., ... Iwasaki, A. (2017). The cellular endosomal protein stannin inhibits intracellular trafficking of human papillomavirus during virus entry. Journal of General Virology, 98(11), 2821-2836. [000954]. https://doi.org/10.1099/jgv.0.000954