2008_Clathrin-_and_Caveolin-Independent_Entry_of_HPV16_involvement_of_TEMs

2008_Clathrin-_and_Caveolin-Independent_Entry_of_HPV16_involvement_of_TEMs

Info iconThis preview shows pages 1–2. Sign up to view the full content.

View Full Document Right Arrow Icon
Clathrin- and Caveolin-Independent Entry of Human Papillomavirus Type 16—Involvement of Tetraspanin- Enriched Microdomains (TEMs) Gilles Spoden 1 , Kirsten Freitag 1 , Matthias Husmann 1 , Klaus Boller 2 , Martin Sapp 3 , Carsten Lambert 1 * , Luise Florin 1 1 Institute for Medical Microbiology and Hygiene, University of Mainz, Mainz, Germany, 2 Paul Ehrlich Institute, Langen, Germany, 3 Department of Microbiology and Immunology, Feist-Weiller Cancer Center, Center for Molecular Tumor Virology, LSU Health Sciences Center, Shreveport, Louisiana, United States of America Abstract Background: Infectious entry of human papillomaviruses into their host cells is an important step in the viral life cycle. For cell binding these viruses use proteoglycans as initial attachment sites. Subsequent transfer to a secondary receptor molecule seems to be involved in virus uptake. Depending on the papillomavirus subtype, it has been reported that entry occurs by clathrin- or caveolin-mediated mechanisms. Regarding human papillomavirus type 16 (HPV16), the primary etiologic agent for development of cervical cancer, clathrin-mediated endocytosis was described as infectious entry pathway. Methodology/Principal Findings: Using immunofluorescence and infection studies we show in contrast to published data that infectious entry of HPV16 occurs in a clathrin- and caveolin-independent manner. Inhibition of clathrin- and caveolin/ raft-dependent endocytic pathways by dominant-negative mutants and siRNA-mediated knockdown, as well as inhibition of dynamin function, did not impair infection. Rather, we provide evidence for involvement of tetraspanin-enriched microdomains (TEMs) in HPV16 endocytosis. Following cell attachment, HPV16 particles colocalized with the tetraspanins CD63 and CD151 on the cell surface. Notably, tetraspanin-specific antibodies and siRNA inhibited HPV16 cell entry and infection, confirming the importance of TEMs for infectious endocytosis of HPV16. Conclusions/Significance: Tetraspanins fulfill various roles in the life cycle of a number of important viral pathogens, including human immunodeficiency virus (HIV) and hepatitis C virus (HCV). However, their involvement in endocytosis of viral particles has not been proven. Our data indicate TEMs as a novel clathrin- and caveolin-independent invasion route for viral pathogens and especially HPV16. Citation: Spoden G, Freitag K, Husmann M, Boller K, Sapp M, et al. (2008) Clathrin- and Caveolin-Independent Entry of Human Papillomavirus Type 16— Involvement of Tetraspanin-Enriched Microdomains (TEMs). PLoS ONE 3(10): e3313. doi:10.1371/journal.pone.0003313 Editor: Peter Sommer, Institut Pasteur Korea, Republic of Korea Received May 19, 2008; Accepted September 10, 2008; Published October 2, 2008 Copyright: ß 2008 Spoden et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding:
Background image of page 1

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Image of page 2
This is the end of the preview. Sign up to access the rest of the document.

This note was uploaded on 11/01/2010 for the course PRC 1234 taught by Professor All during the Spring '10 term at HKU.

Page1 / 15

2008_Clathrin-_and_Caveolin-Independent_Entry_of_HPV16_involvement_of_TEMs

This preview shows document pages 1 - 2. Sign up to view the full document.

View Full Document Right Arrow Icon
Ask a homework question - tutors are online