L-SIGN (CD 209L) is a liver-specific capture receptor for hepatitis C virus

Gardner, Jason P.; Durso, Robert J.; Arrigale, Robert R.; Donovan, Gerald P.; Maddon, Paul J.; Dragic, Tatjana; Olson, William C.

doi:10.1073/pnas.0831128100

Cited by 262 publications

(226 citation statements)

References 44 publications

Supporting

Mentioning

221

Contrasting

Unclassified

Order By: Relevance

“…The ability of E2 to bind to CD81 has been widely documented; however, widespread distribution of CD81 on nonpermissive cells (30) led to the view that other liver-specific molecules must also be involved in facilitating entry (19). Several other cell surface molecules have been reported to bind to native HCV particles or recombinant E2, including the low-density lipoprotein receptor (1,51), dendritic-cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) and liver/lymph nodespecific intercellular adhesion molecule 3-grabbing integrin (L-SIGN or DC-SIGNR) (20,32,42), glycosaminoglycans (4), and scavenger receptor class B type I (SR-B1) (6,44). Despite early doubts about the function of CD81 in HCV entry, data using recently developed assays of retroviral pseudoparticles (HCVpp) and in vitro infectious clones support a central role for CD81 in mediating infection (6,11,29,31).…”

Section: Hepatitis C Virus (Hcv)mentioning

confidence: 99%

Identification of Conserved Residues in the E2 Envelope Glycoprotein of the Hepatitis C Virus That Are Critical for CD81 Binding

Owsianka

Timms

Tarr

et al. 2006

J Virol

229

268

View full text Add to dashboard Cite

Hepatitis C virus (HCV) cell entry involves interaction between the viral envelope glycoprotein E2 and the cell surface receptor CD81. Knowledge of conserved E2 determinants important for successful binding will facilitate development of entry inhibitors designed to block this interaction. Previous studies have assigned the CD81 binding function to a number of discontinuous regions of E2. To better define specific residues involved in receptor binding, a panel of mutants of HCV envelope proteins was generated, where conserved residues within putative CD81 binding regions were sequentially mutated to alanine. Mutant proteins were tested for binding to a panel of monoclonal antibodies and CD81 and for their ability to form noncovalent heterodimers and confer infectivity in the retroviral pseudoparticle (HCVpp) assay. Detection by conformation-sensitive monoclonal antibodies indicated that the mutant proteins were correctly folded. Mutant proteins fell into three groups: those that bound CD81 and conferred HCVpp infectivity, those that abrogated both CD81 binding and HCVpp infectivity, and a final group containing mutants that were able to bind CD81 but were noninfectious in the HCVpp assay. Specific amino acids conserved across all genotypes that were critical for CD81 binding were W420, Y527, W529, G530, and D535. These data significantly increase our understanding of the CD81 receptor-E2 binding process.Hepatitis C virus (HCV) is the sole member of the Hepacivirus genus within the family Flaviviridae. It is a major cause of community-acquired and posttransfusion hepatitis. More than 170 million people worldwide are seropositive for HCV, and only 20% of those infected are able to clear the virus. In the remaining 80% of individuals, the virus persists and can

show abstract

Section: Hepatitis C Virus (Hcv)mentioning

confidence: 99%

Identification of Conserved Residues in the E2 Envelope Glycoprotein of the Hepatitis C Virus That Are Critical for CD81 Binding

Owsianka

Timms

Tarr

et al. 2006

J Virol

229

268

View full text Add to dashboard Cite

show abstract

“…Interestingly, blocking of the interaction between DC and T cells with an anti-DC-SIGN antibody influences allostimulatory properties in T cells [1]. Several recent studies have demonstrated that cross-talk between C-type lectins and TLR can occur [14,32,33], suggesting that simultaneous interaction of pathogens with both receptors can modulate the response by DC. In this context, a recent study indicates that activation of DC by HPV L1-VLP is MyD88 dependent [34].…”

Section: Blocking the Interaction Of L1-vlp With Dc-sign Inhibits Vlpmentioning

confidence: 99%

Role of DC‐SIGN in the activation of dendritic cells by HPV‐16 L1 virus‐like particle vaccine

et al. 2006

View full text Add to dashboard Cite

Dendritic cell-specific intercellular adhesion molecule-grabbing non-integrin (DC-SIGN), a specific C-type lectin expressed on DC, binds and transmits different pathogens to susceptible cells. In the present study, we examined the role of DC-SIGN in the capture of human papillomavirus (HPV) pseudovirions and activation of DC. We demonstrate that HPV virus-like particles (VLP) bind to DC-SIGN expressed on transfected Raji cells and that antibodies against DC-SIGN block this interaction. DC take up VLP, which activate expression of costimulatory markers and cytokines/ chemokines. Although our results indicate that DC-SIGN is not the major receptor for VLP in DC, this interaction contributes to the activation of DC surface antigens (HLA class I) and of various cytokines/chemokines, particularly TNF-a, IL-6, and RANTES. Induction of these markers in DC by VLP was significantly abrogated when binding to DC-SIGN was blocked by anti-DC-SIGN antibodies. These results suggest that DC-SIGN has a functional role in DC activation induced by HPV-16 L1-VLP, and thus highlight new aspects of DC interactions with HPV VLP. IntroductionThe C-type lectin dendritic cell-specific intercellular adhesion molecule-grabbing non-integrin (DC-SIGN; CD209) is a pathogen recognition receptor that interacts with mannose residues of glycoproteins in a calciumdependent manner via its C-terminal carbohydrate recognition domain [1,2]. DC-SIGN acts both as an adhesion molecule and pathogen recognition receptor, facilitating DC binding and internalization of several viruses, including HIV-1 [3].In addition to HIV, DC-SIGN was recently shown to bind a variety of microorganisms such as CMV [4], Ebola virus [5], Dengue virus [6], hepatitis C virus [7,8], simian immunodeficiency virus [9], Leishmania [10], Candida albicans [11], Mycobacterium [12][13][14] and Schistosoma [15]. Some pathogens subvert DC functions to escape immune surveillance [16]. DC-SIGN is abundantly expressed primarily on DC, including those derived from monocytes and those located beneath the genital surface [3].Human papillomavirus (HPV) virus-like particles (VLP) are a promising vaccine candidate for HPV and cervical cancer [17][18][19][20]. Recent clinical trials have shown that VLP afford excellent protection against persistent infection [20,21]. Because of the lack of a suitable cell culture system for in vitro propagation of HPV and the unavailability of virions, HPV VLP have been used as soluble surrogates for native virus particles. The routes of HPV-16 L1-VLP entry in DC and the nature of cellular receptors involved in capture have been studied but remain to be fully characterized. HPV VLP Here, we report that HPV-16 L1-VLP particles bind to DC-SIGN in transfected cell lines, and to a lesser extent in DC, and that this interaction participates in L1-VLPinduced activation of DC. Thus, DC-SIGN is likely involved in DC activation by HPV VLP. Results and discussion HPV L1-VLP bind to DC-SIGN in DC-SIGN-transfected cell linesTo study interactions between L1-VLP and DC-SIGN, we...

show abstract

“…Platelets do not express CD81 (Levy et al, 1998), SR-BI (Rhainds & Brissette, 2004), DC-and L-SIGN (van Kooyk & Geijtenbeek, 2003) or the classical LDL-R (Korporaal et al, 2004;Pedreno et al, 1992), which are putative HCV receptors (Agnello et al, 1999;Gardner et al, 2003;Lozach et al, 2003; Monazahian et al, 1999;Pileri et al, 1998;Pohlmann et al, 2003;Scarselli et al, 2002). Thus, other molecule(s) might mediate the interaction between HCV and platelets.…”

Section: Introductionmentioning

confidence: 99%

“…Viral interaction with platelets is well recognized, as it has been described for other viruses such as herpes simplex virus (Forghani & Schmidt, 1983), Vaccinia virus (Bik et al, 1982), Human immunodeficiency virus 1 (HIV-1) (Lee et al, 1998(Lee et al, , 1993Olinger et al, 2000), echovirus 1 (Xing et al, 2004), hantavirus (Gavrilovskaya et al, 1998) and the flavivirus dengue type 2 (Wang et al, 1995) among others. Several mechanisms have been proposed as contributing to thrombocytopenia, but recently a positive correlation between thrombocytopenia and HCV association with platelets was described (de Almeida et al, 2004), suggesting a direct viral effect on platelet count.Platelets do not express CD81 (Levy et al, 1998), SR-BI (Rhainds & Brissette, 2004), DC-and L-SIGN (van Kooyk & Geijtenbeek, 2003) or the classical LDL-R (Korporaal et al, 2004;Pedreno et al, 1992), which are putative HCV receptors (Agnello et al, 1999;Gardner et al, 2003;Lozach et al, 2003; Monazahian et al, 1999;Pileri et al, 1998;Pohlmann et al, 2003;Scarselli et al, 2002). Thus, other molecule(s) might mediate the interaction between HCV and platelets.…”

mentioning

confidence: 99%

Hepatitis C virus interacts with human platelet glycoprotein VI

Zahn

Jennings

Ouwehand

et al. 2006

Journal of General Virology

View full text Add to dashboard Cite

Hepatitis C virus (HCV) interacts with human platelets in vivo as a potential transport of infectious virions to the target liver. The binding of native viral particles with the platelet membrane glycoprotein VI (GPVI) was analysed. A consistent interaction between HCV from plasma or after purification by two different methods and the recombinant extracellular immunoglobulin (Ig)-like domains of human GPVI (hD1D2) was observed with two independent experimental approaches: pull-down and ELISA assays. Between 2 and 7 % of HCV particles were specifically bound to hD1D2. The binding was inhibited by an anti-hD1D2 in a dose-dependent manner. Human D1D2 interaction with HCV was significantly higher than the murine D1D2, supporting the specificity of the interaction and to the single human domains (D1 and D2), suggesting that both Ig-like domains of the molecule are required for efficient binding. GPVI may be a platelet surface ligand for HCV playing a role in viral transport and persistence. INTRODUCTIONHepatitis C virus (HCV) infection is a global health problem, being a major cause of cirrhosis and hepatocellular carcinoma worldwide. The infection can also lead to a number of serious extra-hepatic manifestations (Major et al., 2001) and the existence of extra-hepatic viral reservoirs, such as lymphocytes, as well as the importance that they might have in the pathophysiology of infection becoming increasingly recognized.HCV infection is also associated with thrombocytopenia. Several investigators have reported HCV association with platelets (de Almeida et al., 2004; Floreani et al., 1996;Li et al., 1994;Nagamine et al., 1996;Silva et al., 1992;Takehara et al., 1994). We have previously shown the interaction of immunoglobulin (Ig) G-free and IgG-complexed HCV with platelets in chronically infected patients (Hamaia et al., 2001). Viral interaction with platelets is well recognized, as it has been described for other viruses such as herpes simplex virus (Forghani & Schmidt, 1983), Vaccinia virus (Bik et al., 1982), Human immunodeficiency virus 1 (HIV-1) (Lee et al., 1998(Lee et al., , 1993Olinger et al., 2000), echovirus 1 (Xing et al., 2004), hantavirus (Gavrilovskaya et al., 1998) and the flavivirus dengue type 2 (Wang et al., 1995) among others. Several mechanisms have been proposed as contributing to thrombocytopenia, but recently a positive correlation between thrombocytopenia and HCV association with platelets was described (de Almeida et al., 2004), suggesting a direct viral effect on platelet count.Platelets do not express CD81 (Levy et al., 1998), SR-BI (Rhainds & Brissette, 2004), DC-and L-SIGN (van Kooyk & Geijtenbeek, 2003) or the classical LDL-R (Korporaal et al., 2004;Pedreno et al., 1992), which are putative HCV receptors (Agnello et al., 1999;Gardner et al., 2003;Lozach et al., 2003; Monazahian et al., 1999;Pileri et al., 1998;Pohlmann et al., 2003;Scarselli et al., 2002). Thus, other molecule(s) might mediate the interaction between HCV and platelets.Preliminary work in the laboratory identified a 6...

show abstract

L-SIGN (CD 209L) is a liver-specific capture receptor for hepatitis C virus

Cited by 262 publications

References 44 publications

Identification of Conserved Residues in the E2 Envelope Glycoprotein of the Hepatitis C Virus That Are Critical for CD81 Binding

Identification of Conserved Residues in the E2 Envelope Glycoprotein of the Hepatitis C Virus That Are Critical for CD81 Binding

Role of DC‐SIGN in the activation of dendritic cells by HPV‐16 L1 virus‐like particle vaccine

Hepatitis C virus interacts with human platelet glycoprotein VI

Contact Info

Product

Resources

About