Different heparan sulfate proteoglycans serve as cellular receptors for human papillomaviruses

被引:198
作者
Shafti-Keramat, S
Handisurya, A
Kriehuber, E
Meneguzzi, G
Slupetzky, K
Kirnbauer, R
机构
[1] Univ Vienna, Sch Med, Div Immunol Allergy & Infect Dis, Lab Viral Oncol,Dept Dermatol, A-1090 Vienna, Austria
[2] Fac Med, U385 INSERM, Nice, France
[3] Austrian Acad Sci, Ctr Mol Med, CEMM, A-1010 Vienna, Austria
关键词
D O I
10.1128/JVI.77.24.13125-13135.2003
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Papillomaviruses replicate in stratified epithelia of skin and mucosa. Infection with certain human papillomavirus (HPV) types is the main cause of anogenital neoplasia, in particular cervical cancer. Early events of papillomavirus infectivity are poorly understood. While heparan sulfate proteoglycans (HSPGs) mediate initial binding to the cell surface, the class of proteins carrying heparan sulfates has not been defined. Here we examined two processes of papillomavirus infection, attachment of virus-like particles (VLP) to cells and infection with authentic HPV type 11 (HPV11) virions. Of the HSPGs, syndecan-1 is the major epithelial form and is strongly upregulated in wound edge keratinocytes. We employed K562 cells, which lack HSPGs except minor amounts of endogenous betaglycan, and stable clones that express cDNAs of syndecan-1, syndecan-4, or glypican-1. Binding of VLP correlated with levels of heparan sulfate on the cell surface. Parental K562 bound HPV16 VLP weakly, whereas all three K562 transfectants demonstrated enhanced binding, with the highest binding capacity observed for syndecan-1-transfected cells, which also expressed the most HSPG. For HPV11 infectivity assays, a high virion inoculum was required to infect K562 cells, whereas ectopic expression of syndecan-1 increased permissiveness eightfold and expression of syndecan-4 or glypican-1 fourfold. Infection of keratinocytes was eliminated by treatment with heparitinase, but not phospholipase C, further implicating the syndecan family of integral membrane proteins as receptor proteins. Human keratinocytes with a homozygous deletion of alpha6 integrin are permissive for HPV11 infection. These results indicate that several HSPGs can serve as HPV receptors and support a putative role for syndecan-1, rather than alpha6 integrin, as a primary receptor protein in natural HPV infection of keratinocytes.
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页码:13125 / 13135
页数:11
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