Epithelial Cells Display Separate Receptors for Papillomavirus VLPs and for Soluble L1 Capsid Protein

Qi, Ying; Shi, Peng; Hengst, Kylie; Evander, Magnus; Park, David; Zhou, Jiang; Frazer, Ian H.

doi:10.1006/viro.1996.0032

Cited by 43 publications

(36 citation statements)

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“…This concept is further supported by the successful application of virus-like particles of other viruses for the characterization of virus-host interactions. Virus-like particle-based binding and entry systems have been developed for papillomavirus (17,24,28,37,42,53), rotavirus (22,23), and Norwalk virus (45,50).…”

Section: Discussionmentioning

confidence: 99%

Binding of Hepatitis C Virus-Like Particles Derived from Infectious Clone H77C to Defined Human Cell Lines

Wellnitz

Klumpp

Barth

et al. 2002

J Virol

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Hepatitis C virus (HCV) is a leading cause of chronic hepatitis in the world. The study of viral entry and infection has been hampered by the inability to efficiently propagate the virus in cultured cells and the lack of a small-animal model. Recent studies have shown that in insect cells, the HCV structural proteins assemble into HCV-like particles (HCV-LPs) with morphological, biophysical, and antigenic properties similar to those of putative virions isolated from HCV-infected humans. In this study, we used HCV-LPs derived from infectious clone H77C as a tool to examine virus-cell interactions. The binding of partially purified particles to human cell lines was analyzed by fluorescence-activated cell sorting with defined monoclonal antibodies to envelope glycoprotein E2. HCV-LPs demonstrated dose-dependent and saturable binding to defined human lymphoma and hepatoma cell lines but not to mouse cell lines. Binding could be inhibited by monoclonal anti-E2 antibodies, indicating that the HCV-LP-cell interaction was mediated by envelope glycoprotein E2. Binding appeared to be CD81 independent and did not correlate with low-density lipoprotein receptor expression. Heat denaturation of HCV-LPs drastically reduced binding, indicating that the interaction of HCV-LPs with target cells was dependent on the proper conformation of the particles. In conclusion, our data demonstrate that insect cell-derived HCV-LPs bind specifically to defined human cell lines. Since the envelope proteins of HCV-LPs are presumably presented in a virion-like conformation, the binding of HCV-LPs to target cells may allow the study of virus-host cell interactions, including the isolation of HCV receptor candidates and antibody-mediated neutralization of binding.Hepatitis C virus (HCV) is a major cause of posttransfusion and community-acquired hepatitis (2, 3, 13, 34). The majority of HCV-infected individuals develop chronic hepatitis that may progress to liver cirrhosis and hepatocellular carcinoma (34, 46). Treatment options for chronic HCV infection are limited, and a vaccine to prevent HCV infection is not available (31,33,34).HCV has been tentatively classified in a separate genus (Hepaticivirus) of the family Flaviviridae (4, 36, 43). The virion contains a positive-stranded RNA genome of approximately 9.6 kb. The genome consists of a highly conserved 5Ј noncoding region followed by a long open reading frame of 9,030 to 9,099 nucleotides (nt) that is translated into a single polyprotein of 3,010 to 3030 amino acids (aa) (4, 36). Processing of the polyprotein occurs with a combination of host and viral proteases. The HCV structural proteins comprise the putative nucleocapsid or core protein and the two envelope glycoproteins, E1 and E2 (4, 36, 43). The cleavage of structural proteins from the polyprotein is catalyzed by a host signal peptidase. Envelope proteins E1 and E2 are transmembrane proteins consisting of a large N-terminal ectodomain and a C-terminal hydrophobic anchor. E1 and E2 are posttranslationally modified by extensive N-linke...

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Section: Discussionmentioning

confidence: 99%

Binding of Hepatitis C Virus-Like Particles Derived from Infectious Clone H77C to Defined Human Cell Lines

Wellnitz

Klumpp

Barth

et al. 2002

J Virol

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“…VLPs with a density of 1.28 g/ml were collected and dialyzed extensively against PBS (13). Construction of baculovirus encoding HPV6bL1, HPV11L1, HPV16L1, bovine PV1L1 (BPV1L1), BPV1L1/HIVIIIbp18I10CTL (p18VLPs), and BPV1L1/HPV16E7CTL (E7VLPs) recombinant protein has been described elsewhere (13,26,27). Samples were subjected to analysis by transmission electron microscopy and immunoblotting to confirm the identity and integrity of the VLPs.…”

Section: Production Of Rvlpsmentioning

confidence: 99%

IL-10 Mediates Suppression of the CD8 T Cell IFN-γ Response to a Novel Viral Epitope in a Primed Host

Liu

Hardy

et al. 2003

The Journal of Immunology

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Priming to Ag can inhibit subsequent induction of an immune response to a new epitope incorporated into that Ag, a phenomenon referred to as original antigenic sin. In this study, we show that prior immunity to a virus capsid can inhibit subsequent induction of the IFN-γ effector T cell response to a novel CD8-restricted antigenic epitope associated with the virus capsid. Inhibition does not involve Ab to the virus capsid, as it is observed in animals lacking B cells. CD8-restricted virus-specific T cell responses are not required, as priming to virus without CTL induction is associated with inhibition. However, IL-10−/− mice, in contrast to IL-10+/+ mice, generate CD8 T cell and Ab responses to novel epitopes incorporated into a virus capsid, even when priming to the capsid has resulted in high titer Ab to the capsid. Furthermore, capsid-primed mice, unable to mount a response to a novel epitope in the capsid protein, are nevertheless able to respond to the same novel epitope delivered independently of the capsid. Thus, inhibition of responsiveness to a novel epitope in a virus-primed animal is a consequence of secretion of IL-10 in response to presented Ag, which inhibits local generation of new CD8 IFN-γ-secreting effector T cells. Induction of virus- or tumor Ag-specific CD8 effector T cells in the partially Ag-primed host may thus be facilitated by local neutralization of IL-10.

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“…According to previous estimates (25,36), only 20,000 VLPs can bind to a given cell at saturation, whereas proteoglycans are common on all cells, with up to 10 6 molecules per cell (37). It is therefore tempting to speculate that a specific proteoglycan may mediate virion attachment.…”

mentioning

confidence: 99%

“…Virus-like particles (VLPs) generated by synthesis of the capsid proteins L1 and L2 in various expression systems (18,27,35) have shed some light on the mode of interaction between the cell surface and the viral capsid (26,24,36). It was demonstrated that the binding moiety on cell surfaces is highly conserved within the animal kingdom and that, with few exceptions, all cell lines tested were able to bind VLPs (25,36). In addition, VLPs generated from the capsid proteins of different papillomaviruses were shown to compete for the same binding receptor (26).…”

mentioning

confidence: 99%

Human Papillomavirus Infection Requires Cell Surface Heparan Sulfate

Giroglou

Florin

Schäfer

et al. 2001

J Virol

480

418

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Using pseudoinfection of cell lines, we demonstrate that cell surface heparan sulfate is required for infection by human papillomavirus type 16 (HPV-16) and HPV-33 pseudovirions. Pseudoinfection was inhibited by heparin but not dermatan or chondroitin sulfate, reduced by reducing the level of surface sulfation, and abolished by heparinase treatment. Carboxy-terminally deleted HPV-33 virus-like particles still bound efficiently to heparin. The kinetics of postattachment neutralization by antiserum or heparin indicated that pseudovirions were shifted on the cell surface from a heparin-sensitive into a heparin-resistant mode of binding, possibly involving a secondary receptor. Alpha-6 integrin is not a receptor for HPV-33 pseudoinfection.Papillomaviruses are highly species-and tissue-specific viruses primarily found in higher vertebrates. They infect exclusively basal cells of epithelia and induce squamous epithelial and fibroepithelial tumors, e.g., warts (papillomas) and condylomata. To date, more than a hundred human papillomaviruses (HPVs) have been identified, and some of them are strongly associated with malignant epithelial lesions, particularly genital carcinoma (for a review, see reference 13). Infectious virions recovered from naturally occurring warts of rab-

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Epithelial Cells Display Separate Receptors for Papillomavirus VLPs and for Soluble L1 Capsid Protein

Cited by 43 publications

References 0 publications

Binding of Hepatitis C Virus-Like Particles Derived from Infectious Clone H77C to Defined Human Cell Lines

Binding of Hepatitis C Virus-Like Particles Derived from Infectious Clone H77C to Defined Human Cell Lines

IL-10 Mediates Suppression of the CD8 T Cell IFN-γ Response to a Novel Viral Epitope in a Primed Host

Human Papillomavirus Infection Requires Cell Surface Heparan Sulfate

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