Abstract
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.
| Original language | English (US) |
|---|---|
| Article number | e68379 |
| Journal | PloS one |
| Volume | 8 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jul 4 2013 |
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All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)
- Agricultural and Biological Sciences(all)
- General
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Differential Dependence on Host Cell Glycosaminoglycans for Infection of Epithelial Cells by High-Risk HPV Types. / Cruz, Linda; Meyers, Craig.
In: PloS one, Vol. 8, No. 7, e68379, 04.07.2013.Research output: Contribution to journal › Article
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
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.
UR - http://www.scopus.com/inward/record.url?scp=84879831306&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84879831306&partnerID=8YFLogxK
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 -