Human Cytomegalovirus Binding to DC-SIGN Is Required for Dendritic Cell Infection and Target Cell trans-Infection

Halary, Franck; Amara, Ali; Lortat‐Jacob, Hugues; Messerle, Martin; Delaunay, Thierry; Houles, Corinne; Fieschi, Franck; Arenzana-Seisdedos, Fernando; Moreau, Jean François; Déchanet‐Merville, Julie

doi:10.1016/s1074-7613(02)00447-8

Cited by 329 publications

(329 citation statements)

References 43 publications

Supporting

Mentioning

321

Contrasting

Unclassified

Order By: Relevance

“…Although DC-SIGN is not a requisite receptor for HIV fusion, DC-SIGN expression increases the susceptibility of cells to HIV by reducing the threshold level of fusion receptor expression, thereby rendering otherwise impermissive cells susceptible to HIV infection (40). Similarly, DC-SIGN and L-SIGN confer permissivity to cells that are otherwise refractory to infection by Ebola and cytomegalovirus pseudoviruses (9,11).…”

Section: Discussionmentioning

confidence: 99%

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

Gardner

Durso

Arrigale

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

262

221

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

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

Gardner

Durso

Arrigale

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

262

221

View full text Add to dashboard Cite

“…The C type lectins, DC-SIGN (dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin; CD209) and L-SIGN (DC-SIGNR; liver and lymph node-specific; CD209L), function as capture receptors for several viruses, including HIV type 1 (HIV-1) (34), Ebola virus (35), cytomegalovirus (36), and dengue virus (37). Both L-SIGN and DC-SIGN have an extracellular C-terminal region that contains a calcium-dependent carbohydrate recognition domain (CRD) and a membrane-proximal heptad-repeat region important for oligomerization (38)(39)(40)(41).…”

Section: H Epatitis C Virus (Hcv) Is the Etiologic Agent Of Non-a Non-bmentioning

confidence: 99%

“…HCV capture by SIGN molecules depends on the presence of the CRD, indicating that recognition of high mannose oligosaccharides in the viral envelope glycoproteins is critical for binding. The specificity of this interaction is underscored by observations that (i) other C type lectins, such as langerin, CD23, and CLEC-1͞2, do not bind HCV E2 (45,46); (ii) glycosylated envelope proteins of several viruses show little or no avidity for SIGN molecules (36,47); and (iii) anti-L-SIGN and anti-DC-SIGN mAbs as well as mannan inhibit soluble E2 and HCV capture.…”

Section: H Epatitis C Virus (Hcv) Is the Etiologic Agent Of Non-a Non-bmentioning

confidence: 99%

L-SIGN (CD209L) and DC-SIGN (CD209) mediate transinfection of liver cells by hepatitis C virus

Cormier

Durso

Tsamis

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

187

163

View full text Add to dashboard Cite

Target cell tropism of enveloped viruses is regulated by interactions between viral and cellular factors during transmission, dissemination, and replication within the host. Binding of viral envelope glycoproteins to specific cell-surface receptors determines susceptibility to viral entry. However, a number of cell-surface molecules bind viral envelope glycoproteins without mediating entry. Instead, they serve as capture receptors that disseminate viral particles to target organs or susceptible cells. We and others recently demonstrated that the C type lectins L-SIGN and DC-SIGN capture hepatitis C virus (HCV) by specific binding to envelope glycoprotein E2. In this study, we use an entry assay to demonstrate that HCV pseudoviruses captured by L-SIGN؉ or DC-SIGN؉ cells efficiently transinfect adjacent human liver cells. Virus capture and transinfection require internalization of the SIGN-HCV pseudovirus complex. In vivo, L-SIGN is largely expressed on endothelial cells in liver sinusoids, whereas DC-SIGN is expressed on dendritic cells. Capture of circulating HCV particles by these SIGN؉ cells may facilitate virus infection of proximal hepatocytes and lymphocyte subpopulations and may be essential for the establishment of persistent infection.H epatitis C virus (HCV) is the etiologic agent of non-A non-B hepatitis in humans (1, 2). Only Ϸ15% of infected individuals clear the virus, and Ϸ170 million people worldwide are persistently infected with HCV (3, 4). These individuals may remain asymptomatic or may develop chronic hepatitis or cirrhosis, the latter often leading to hepatocellular carcinoma (5). Hepatocytes are the primary target cells for HCV infection (6-8). Virus-like particles have been visualized in liver biopsies of HCVϩ individuals (9-11), and in vitro infection, albeit inefficient, of primary hepatocytes and hepatoma cells has been documented (12)(13)(14). The existence of extrahepatic reservoirs of HCV is suggested by the detection of viral RNA in serum and peripheral blood mononuclear cells of HCVϩ individuals (15)(16)(17). Both B and T lymphocytes appear to be infected in vivo, which is supported by in vitro infection of B and T cell lines (7,8,18). One study, however, shows that replicating forms of HCV RNA are restricted to hepatocytes, whereas only nonreplicating forms are present in B lymphocytes, and none are in T lymphocytes (6).HCV envelope glycoproteins E1 and E2 mediate entry into target cells. We and others recently demonstrated that unmodified E1E2 heterodimers reach the cell surface and are incorporated into retroviral pseudoparticles, which can infect primary hepatocytes and some hepatoma cell lines (19 -22). Use of the soluble E2 ectodomain as a surrogate model for studying HCV interactions with cell-surface molecules has identified several potential HCV entry receptors, including CD81, scavenger receptor class B type 1, low-density lipoprotein receptor, and glycosaminoglycans (22-24). Several groups, including ours, have shown that CD81 is necessary but not sufficient for HCV pseu...

show abstract

“…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].…”

Section: Introductionmentioning

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

Human Cytomegalovirus Binding to DC-SIGN Is Required for Dendritic Cell Infection and Target Cell trans-Infection

Cited by 329 publications

References 43 publications

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

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

L-SIGN (CD209L) and DC-SIGN (CD209) mediate transinfection of liver cells by hepatitis C virus

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

Contact Info

Product

Resources

About