α6 integrin is not the obligatory cell receptor for bovine papillomavirus type 4

Sibbet, Gary; Romero-Graillet, Christine; Meneguzzi, Guerríno; Campo, M. Saveria

doi:10.1099/0022-1317-81-6-1629

Cited by 21 publications

(12 citation statements)

References 47 publications

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“…The neutralising activity can be abrogated by absorbing the immune sera with L2 or L2a [39,54]. Virus neutralisation by anti-L2 antibodies prevents viral DNA replication, but not virus entry into the cell since viral DNA is detected at the virus injection site; the mechanisms underlying viral neutralisation are still unknown [124]. Similar results were achieved with the L1 portion of BPV-1 although in this case the production of neutralising antibodies was doubtful.…”

Section: Immunity and Vaccinessupporting

confidence: 68%

Bovine papillomaviruses, papillomas and cancer in cattle

Borzacchiello¹,

Roperto²

2008

Vet. Res.

169

149

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-Bovine papillomaviruses (BPV) are DNA oncogenic viruses inducing hyperplastic benign lesions of both cutaneous and mucosal epithelia in cattle. Ten (BPV 1-10) different viral genotypes have been characterised so far. BPV 1-10 are all strictly species-specific but BPV 1/2 may also infect equids inducing fibroblastic tumours. These benign lesions generally regress but may also occasionally persist, leading to a high risk of evolving into cancer, particularly in the presence of environmental carcinogenic co-factors. Among these, bracken fern is the most extensively studied. The synergism between immunosuppressants and carcinogenic principles from bracken fern and the virus has been experimentally demonstrated for both urinary bladder and alimentary canal cancer in cows whose diets were based on this plant. BPV associated tumours have veterinary and agricultural relevance in their own right, although they have also been studied as a relevant model of Human papillomavirus (HPV). Recent insights into BPV biology have paved the way to new fields of speculation on the role of these viruses in neoplastic transformation of cells other than epithelial ones. This review will briefly summarise BPV genome organization, will describe in greater detail the functions of viral oncoproteins, the interaction between the virus and co-carcinogens in tumour development; relevant aspects of immunity and vaccines will also be discussed.

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Section: Immunity and Vaccinessupporting

confidence: 68%

Bovine papillomaviruses, papillomas and cancer in cattle

Borzacchiello¹,

Roperto²

2008

Vet. Res.

169

149

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“…␣6 integrin has been proposed as the binding receptor for HPV6 VLP (15). However, further analysis has revealed that ␣6 integrin is not required for HPV11 VLP binding, HPV33 pseudoinfection, or BPV type 4 (BPV4) infection (17,21,48). To further address this issue, we performed attachment assays using VLP of high-risk HPV16 and human epidermal keratinocytes as appropriate target cells.…”

Section: Resultsmentioning

confidence: 99%

“…Infection with native papillomaviruses or pseudovirions or VLP uptake into intracellular vesicles has been reported to occur via either clathrin-or caveolae-mediated endocytosis, with delayed uptake kinetics (4,11,13,33,39,56). ␣6 integrin was proposed as a putative papillomavirus receptor based on the requirement for HPV6 VLP binding to cells, although this has been questioned (15,48). However, many models suffer from the mis-match of virus and host cells and the difficulties in distinguishing protein uptake from authentic papillomavirus infection.…”

mentioning

confidence: 99%

Different Heparan Sulfate Proteoglycans Serve asCellular Receptors for HumanPapillomaviruses

Shafti-Keramat

Handisurya

Kriehuber

et al. 2003

J Virol

Self Cite

238

198

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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 ␣6 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 ␣6 integrin, as a primary receptor protein in natural HPV infection of keratinocytes.Papillomaviruses comprise a large group of species-and tissue-specific DNA tumor viruses found in higher vertebrates from chaffinches to humans and include more than 90 known human papillomavirus (HPV) genotypes. Papillomaviruses cause mainly benign epithelial papillomas or warts on skin and mucosa (condylomata acuminata). Several high-risk HPV types, most often HPV type 16 (HPV16), are the primary etiologic agents for anogenital malignancy, in particular cervical cancer, which is the second most common cause of cancerrelated deaths in women worldwide (41, 57). The papillomavirus virion consists of a nonenveloped capsid comprised of the L1 major and L2 minor structural proteins surrounding a minichromosome of ϳ8 kb of double-stranded closed circular and histone-associated DNA. Even in the absence of other viral proteins, the L1 protein self-assembles into empty capsids or virus-like particles (VLP) (24). Subunit vaccines based on VLP have been developed, and prophylactic immunizations have demonstrated safety and efficacy in preventing papillomavirus infection and associated neoplasia (18,23,25,28,44).Papillomaviruses do not complete their life cycle leading to pr...

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“…Clearly the interaction of L1 VLPs with the cell surface is distinct from that of L2 residues 13 to 31, which bind to ϳ45,000 receptors per HeLa cell with a K d of ϳ1 nM, and the interaction is unaffected by heparinase or trypsin pretreatment. Integrin ␣ 6 was initially identified as a receptor (17,32) for HPV6 L1 VLPs, but it is not obligate (44). Several viruses can use alternate receptors to enter the same cell type: for example, three receptors (HveA, -B, and -C) have been described for herpes simplex virus type 1 (18,33), and foot-and-mouth disease virus exploits ␣ v ␤ 6 integrin, but in certain situations can also use heparan sulfate glycosaminoglycans (GAGs) (1, 3).…”

Section: Discussionmentioning

confidence: 99%

Cell Surface-Binding Motifs of L2 That Facilitate Papillomavirus Infection

Yang¹,

Day

Yutzy³

et al. 2003

J Virol

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Human papillomavirus type 16 (HPV16) is the primary etiologic agent of cervical carcinoma, whereas bovine papillomavirus type 1 (BPV1) causes benign fibropapillomas. However, the capsid proteins, L1 and L2, of these divergent papillomaviruses exhibit functional conservation. A peptide comprising residues 1 to 88 of BPV1 L2 binds to a variety of cell lines, but not to the monocyte-derived cell line D32, and blocks BPV1 infection of mouse C127 cells. Residues 13 to 31 of HPV16 L2 and BPV1 L2 residues 1 to 88 compete for binding to the cell surface, and their binding, unlike that of HPV16 L1/L2 virus-like particles, is unaffected by heparinase or trypsin pretreatment of HeLa cells. A fusion of HPV16 L2 peptide 13-31 and GFP binds (K d , ϳ1 nM) to ϳ45,000 receptors per HeLa cell. Furthermore, mutation of L2 residues 18 and 19 or 21 and 22 significantly reduces both the ability of the HPV16 L2 13-31-GFP fusion protein to bind to SiHa cells and the infectivity of HPV16 pseudovirions. Antibody to BPV1 L2 peptides comprising residues 115 to 135 binds to intact BPV1 virions, but fails to neutralize at a 1:10 dilution. However, deletion of residues 91 to 129 from L2 abolishes the infectivity of BPV1, but not their binding to the cell surface. In summary, L2 residues 91 to 129 contain epitopes displayed on the virion surface and are required for infection, but not virion binding to the cell surface. Upon the binding of papillomavirus to the cell surface, residues 13 to 31 of L2 interact with a widely expressed, trypsin-and heparinase-resistant cell surface molecule and facilitate infection.The infectious process for most viruses, including papillomavirus, is poorly understood. However, in the last decade, a plethora of primary viral receptors have been identified (reviewed in reference 1). Viruses adhere to the target cells via these primary receptors, but their uptake and transport to the site of viral replication often require interaction with other secondary viral receptors (1).The papillomavirus capsid comprises two genetically unrelated viral proteins called L1 and L2 that surround the ϳ8-kb histone-bound, closed circular viral genomic DNA (14). Expression of the major capsid protein L1 results in Tϭ7 viruslike particles (VLPs) formed from 72 petameric L1 capsomers (21, 29). Three-dimensional image reconstructions and the ϳ30:1 ratio of L1 and L2 in native bovine papillomavirus type 1 (BPV1) suggest that the L2 minor capsid protein is located in the center of the pentavalent capsomers at the virion vertices (46). Both L1 and L2 are necessary for efficient production of infectious viruses in vivo, with L2 functioning in both encapsidation and the infectious process (36, 37, 52).Papillomaviruses bind via L1 to cells derived from a wide variety of tissues and species (34, 40). While papillomavirus pseudovirions lacking L2 are infectious (45), recent reports suggest that L2 also can bind to the cell surface, resulting in its internalization (28), and that L2 is critical to the infectious process (36, 47). Furthermore, ant...

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α6 integrin is not the obligatory cell receptor for bovine papillomavirus type 4

Cited by 21 publications

References 47 publications

Bovine papillomaviruses, papillomas and cancer in cattle

Bovine papillomaviruses, papillomas and cancer in cattle

Different Heparan Sulfate Proteoglycans Serve asCellular Receptors for HumanPapillomaviruses

Cell Surface-Binding Motifs of L2 That Facilitate Papillomavirus Infection

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