Analysis of the infectious entry pathway of human papillomavirus type 33 pseudovirions

Virology. 2002 Aug 1;299(2):279-287. doi: 10.1006/viro.2001.1493.


Human papillomavirus type 33 (HPV-33) pseudovirus infection is a slow process dependent on the initial interaction with cell-surface heparan sulfate (T. Giroglou, L. Florin, F. Schafer, R. E. Streeck, and M. Sapp, 2001a, J. Virol. 75, 1565-1570). We have now further dissected the initial steps of pseudovirus uptake using removal of cell-surface proteoglycans and selective inhibition of entry pathways. Treatment of cells with heparinase I, but not with phosphoinositol-specific phospholipase C (PIPLC), prevented binding of papillomavirus-like particles and infection with HPV-33 pseudovirions, indicating that GPI-linked proteoglycans (glypicans) are not required for productive infection. The slow entry of pseudovirions was inhibited by cytochalasin D and nocodazole in a concentration-dependent manner, suggesting actin polymerization and intact microtubuli be required. Inhibitors of the caveolae-mediated uptake did not significantly affect pseudoinfection. Interestingly, pseudoinfection was blocked by selective inhibitors of endosomal acidification up to 12 h postinfection. Together, our results suggest that binding of HPV pseudovirions to heparan sulfate proteoglycans, most likely syndecans, is followed by delayed internalization via the endosomal pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Animals
  • Anti-Bacterial Agents / pharmacology
  • COS Cells
  • HeLa Cells
  • Heparan Sulfate Proteoglycans / physiology
  • Humans
  • Macrolides*
  • Microtubules / physiology
  • Nystatin / pharmacology
  • Papillomaviridae / physiology*
  • Virion / physiology*


  • Actins
  • Anti-Bacterial Agents
  • Heparan Sulfate Proteoglycans
  • Macrolides
  • Nystatin
  • bafilomycin A1