Binding of human papilloma virus L1 virus-like particles to dendritic cells is mediated through heparan sulfates and induces immune activation

Witte, Lot de; Zoughlami, Younes; Aengeneyndt, Birgit; Gourichon, David; Kooyk, Yvette van; Gissmann, Lutz; Geijtenbeek, Teunis B. H.

doi:10.1016/j.imbio.2007.09.006

Cited by 30 publications

(23 citation statements)

References 31 publications

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“…Nevertheless, it is important to emphasize that the "perfect" microbicide will likely be composed of several anti-HIV-1 agents that target viral proteins other than gp120 (i.e., RT) and therefore should neutralize emerging syndecan-1-Fc-resistant HIV-1 variants. Another advantage of using a syndecan-Fc hybrid molecule as a microbicide is that many sexually transmitted pathogens also exploit syndecans for host colonization, such as HSV (7), HPV (13,37), and Neisseria gonorrhoeae (15,41). Supporting this hypothesis, we found that the syndecan-Fc hybrid molecule efficiently blocks HSV infection (Fig.…”

Section: Discussionsupporting

confidence: 71%

“…The sulfation pattern of HSs dictates the ligand specificity of syndecans (1). HSPG, including syndecans, serve as receptors for human deficiency virus type-1 (HIV-1) (16), herpes simplex virus (HSV) (7), human papillomavirus (HPV) (13,37), and human T-lymphotropic virus type 1 (HTLV-1) (19,20). Pretreatment of target cells such as macrophages with heparinase, an enzyme that removes HS moieties from syndecans, significantly reduces HIV-1 infectivity (35).…”

mentioning

confidence: 99%

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Syndecan-Fc Hybrid Molecule as a PotentIn VitroMicrobicidal Anti-HIV-1 Agent

Bobardt¹,

Chatterji²,

Schaffer

et al. 2010

Antimicrob Agents Chemother

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Section: Discussionsupporting

confidence: 71%

mentioning

confidence: 99%

Syndecan-Fc Hybrid Molecule as a PotentIn VitroMicrobicidal Anti-HIV-1 Agent

Bobardt¹,

Chatterji²,

Schaffer

et al. 2010

Antimicrob Agents Chemother

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“…Furthermore, we examined whether L2 plays a role in immune escape of HPV16 through deregulation of the PI3K pathway in LC, a mechanism implicated in our earlier studies (18). LC exposed to HPV16L1 VLP did not induce the activation, i.e., phosphorylation of PI3K, while exposure to HPV16L1L2 VLP highly induced the activation of PI3K in LC compared with that detected in untreated LC (Fig.…”

Section: Lc Activate Pi3k But Down-regulate Akt After Exposure To Hpvmentioning

confidence: 86%

A Major Role for the Minor Capsid Protein of Human Papillomavirus Type 16 in Immune Escape

Fahey¹,

Raff²,

Silva

et al. 2009

The Journal of Immunology

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High-risk human papillomavirus (HPV) infection of the cervical epithelium is causally linked with the generation of cervical cancer. HPV does not activate Langerhans cells (LC), the APC at the site of infection, leading to immune evasion. The HPV protein responsible for inducing this immune escape has not been determined. We demonstrate that LC exposed to the minor capsid protein L2 in HPV16L1L2 virus-like particles do not phenotypically or functionally mature. However, HPV16L1 virus-like particles significantly induce activation of LC. Our data suggest that the L2 protein plays a specific role in the induction of this immune escape of HPV16 through the manipulation of LC. This novel function is the first immune modulating action attributed to the L2 protein and adds significantly to our understanding of the mechanism of HPV immune escape.

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“…For instance, HS mediates HSV-1 transport on filopodia during surfing (17) and negatively regulates virus-induced membrane fusion (14). Likewise, for human papilloma virus, HS proteoglycans play a key role in the activation of immune response, an important aspect for both vaccine development and human papilloma virus pathogenesis (18). Similarly, HS expressed on spermatozoa plays a key role in the capture of human immunodeficiency virus (HIV) and its transmission to dendritic, macrophage, and T cells (19).…”

mentioning

confidence: 99%

Anti-heparan Sulfate Peptides That Block Herpes Simplex Virus Infection in Vivo

Tiwari

Liu

Vályi-Nagy

et al. 2011

Journal of Biological Chemistry

167

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Heparan sulfate (HS) and its highly modified form, 3-O-sulfated heparan sulfate (3-OS HS), contribute strongly to herpes simplex virus type-1 (HSV-1) infection in vitro. Here we report results from a random M13-phage display library screening to isolate 12-mer peptides that bind specifically to HS, 3-OS HS, and block HSV-1 entry. The screening identified representative candidates from two-different groups of anti-HS peptides with high positive charge densities. Group 1, represented by G1 peptide (LRSRTKIIRIRH), belongs to a class with alternating charges (XRXRXKXXRXRX), and group 2, represented by G2 peptide (MPRRRRIRRRQK), shows repetitive charges (XXR-RRRXRRRXK). Viral entry and glycoprotein D binding assays together with fluorescent microscopy data indicated that both G1 and G2 were potent in blocking HSV-1 entry into primary cultures of human corneal fibroblasts and CHO-K1 cells transiently expressing different glycoprotein D receptors. Interestingly, G2 peptide isolated against 3-OS HS displayed wider ability to inhibit entry of clinically relevant strains of HSV-1 and some divergent members of herpesvirus family including cytomegalovirus and human herpesvirus-8. To identify functional residues within G1 and G2, we performed point mutations and alanine-scanning mutagenesis. Several arginine and a lysine residues were needed for anti-HSV-1 activity, suggesting the importance of the positively charged residues in virus-cell binding and virus-induced membrane fusion. In vivo administration of G1 or G2 peptide as a prophylactic eye drop completely blocked HSV-1 spread in the mouse cornea as evident by immunohistochemistry. This result also highlights an in vivo significance of HS and 3-OS HS during ocular herpes infection.

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Binding of human papilloma virus L1 virus-like particles to dendritic cells is mediated through heparan sulfates and induces immune activation

Cited by 30 publications

References 31 publications

Syndecan-Fc Hybrid Molecule as a PotentIn VitroMicrobicidal Anti-HIV-1 Agent

Syndecan-Fc Hybrid Molecule as a PotentIn VitroMicrobicidal Anti-HIV-1 Agent

A Major Role for the Minor Capsid Protein of Human Papillomavirus Type 16 in Immune Escape

Anti-heparan Sulfate Peptides That Block Herpes Simplex Virus Infection in Vivo

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