TY - JOUR
T1 - Differential Dependence on Host Cell Glycosaminoglycans for Infection of Epithelial Cells by High-Risk HPV Types
AU - Cruz, Linda
AU - Meyers, Craig
N1 - Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 2013/7/4
Y1 - 2013/7/4
N2 - Human papillomavirus (HPV) infection is the leading cause of cervical cancer world-wide. Here, we show that native HPV particles produced in a differentiated epithelium have developed different strategies to infect the host. Using biochemical inhibition assays and glycosaminoglycan (GAG)-negative cells, we show that of the four most common cancer-causing HPV types, HPV18, HPV31, and HPV45 are largely dependent on GAGs to initiate infection. In contrast, HPV16 can bind and enter through a GAG-independent mechanism. Infections of primary human keratinocytes, natural host cells for HPV infections, support our conclusions. Further, this renders the different virus types differentially susceptible to carrageenan, a microbicide targeting virus entry. Our data demonstrates that ordered maturation of papillomavirus particles in a differentiating epithelium may alter the virus entry mechanism. This study should facilitate a better understanding of the attachment and infection by the main oncogenic HPV types, and development of inhibitors of HPV infection.
AB - Human papillomavirus (HPV) infection is the leading cause of cervical cancer world-wide. Here, we show that native HPV particles produced in a differentiated epithelium have developed different strategies to infect the host. Using biochemical inhibition assays and glycosaminoglycan (GAG)-negative cells, we show that of the four most common cancer-causing HPV types, HPV18, HPV31, and HPV45 are largely dependent on GAGs to initiate infection. In contrast, HPV16 can bind and enter through a GAG-independent mechanism. Infections of primary human keratinocytes, natural host cells for HPV infections, support our conclusions. Further, this renders the different virus types differentially susceptible to carrageenan, a microbicide targeting virus entry. Our data demonstrates that ordered maturation of papillomavirus particles in a differentiating epithelium may alter the virus entry mechanism. This study should facilitate a better understanding of the attachment and infection by the main oncogenic HPV types, and development of inhibitors of HPV infection.
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U2 - 10.1371/journal.pone.0068379
DO - 10.1371/journal.pone.0068379
M3 - Article
C2 - 23861898
AN - SCOPUS:84879831306
VL - 8
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 7
M1 - e68379
ER -