The haemagglutinin protein is an important determinant of measles virus tropism for dendritic cells in vitro

Ohgimoto, Shinji; Ohgimoto, Kaori; Niewiesk, Stefan; Klagge, Ingo M.; Pfeuffer, Joanna; Johnston, Ian; Schneider‐Schaulies, Jürgen; Weidmann, Armin; Meulen, Volker ter; Schneider‐Schaulies, Sibylle

doi:10.1099/0022-1317-82-8-1835

Cited by 56 publications

(64 citation statements)

References 41 publications

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“…Inhibition by MxA is cell-type-specific (24,25,34), and IFN has a limited ability to interfere with MV replication in PBMCs (31,35). Little infectious MV is produced during the first 1-3 d of DC infection, but, with maturation and T cell activation syncytia-formation, virus production and cell death are reported (10,13,36).…”

Section: Discussionmentioning

confidence: 99%

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Gene expression patterns in dendritic cells infected with measles virus compared with other pathogens

Zilliox

Parmigiani

Griffin

2006

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

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Gene expression patterns supply insight into complex biological networks that provide the organization in which viruses and host cells interact. Measles virus (MV) is an important human pathogen that induces transient immunosuppression followed by life-long immunity in infected individuals. Dendritic cells (DCs) are potent antigen-presenting cells that initiate the immune response to pathogens and are postulated to play a role in MV-induced immunosuppression. To better understand the interaction of MV with DCs, we examined the gene expression changes that occur over the first 24 h after infection and compared these changes to those induced by other viral, bacterial, and fungal pathogens. There were 1,553 significantly regulated genes with nearly 60% of them down-regulated. MV-infected DCs up-regulated a core of genes associated with maturation of antigen-presenting function and migration to lymph nodes but also included genes for IFN-regulatory factors 1 and 7, 2 5 oligoadenylate synthetase, Mx, and TNF superfamily proteins 2, 7, 9, and 10 (TNF-related apoptosisinducing ligand). MV induced genes for IFNs, ILs, chemokines, antiviral proteins, histones, and metallothioneins, many of which were also induced by influenza virus, whereas genes for protein synthesis and oxidative phosphorylation were down-regulated. Unique to MV were the induction of genes for a broad array of IFN-␣s and the failure to up-regulate dsRNA-dependent protein kinase. These results provide a modular view of common and unique DC responses after infection and suggest mechanisms by which MV may modulate the immune response.immunosuppression ͉ IFN ͉ microarray ͉ dsRNA-dependent protein kinase

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Section: Discussionmentioning

confidence: 99%

“…The H glycoprotein is a determinant of MV infection of DCs (36) and can bind to Toll-like receptor-2 on macrophages (44) and to the MV receptors CD46 and SLAM (45). DCs express CD46 and increasing amounts of SLAM with differentiation (45), and the Chicago-1 strain of MV can use both receptors.…”

Section: Discussionmentioning

confidence: 99%

Gene expression patterns in dendritic cells infected with measles virus compared with other pathogens

Zilliox

Parmigiani

Griffin

2006

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

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“…Various evidence has been accumulated indicating that subtle differences in the envelope proteins of MV can play a role in altering the tropism, virus uptake, cell-to-cell fusion and pathogenicity (Bartz et al, 1996;Bieback et al, 2002;Hsu et al, 1998;Johnston et al, 1999;Lecouturier et al, 1996;Moeller et al, 2001;Moll et al, 2001;Ohgimoto et al, 2001;Plemper et al, 2002;Shibahara et al, 1994;Takeuchi et al, 2002). To investigate the molecular basis for the differential spread of MV wild-types in cultures of HUVECs, we will further analyse the sequences of the envelope genes of the MV wildtypes and intend functional studies with corresponding recombinant viruses.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, the signalling lymphocytic activation molecule (SLAM, CD150) has been identified as a common receptor interacting with MV vaccine as well as wild-type strains (Erlenhoefer et al, 2001(Erlenhoefer et al, , 2002Hsu et al, 2001; Ono et al, 2001a, b;Tatsuo et al, 2000). SLAM is expressed on human B cell lines, primary activated B and T cells, memory cells and activated monocytes and monocyte-derived dendritic cells (Cocks et al, 1995;Minagawa et al, 2001;Ohgimoto et al, 2001;Polacino et al, 1996;Punnonen et al, 1997), and its usage as a receptor can explain the tropism of wild-type MV for such cells, but not for epithelial, endothelial and neural cells, such as neurons, oligodendrocytes and astrocytes, which do not express SLAM (McQuaid & Cosby, 2002). On monocytes, the expression of SLAM is induced after infection with MV or treatment with UV-inactivated MV (Minagawa et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

CD46- and CD150-independent endothelial cell infection with wild-type measles viruses

Andrés¹,

Obojes²,

Kim

et al. 2003

Journal of General Virology

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Measles virus (MV) infects endothelial cells of the skin, the brain and other organs during acute or persistent infections. Endothelial cells are supposed to play an important role in virus spread from the blood stream to surrounding tissues. CD46 and CD150 (signalling lymphocytic activation molecule, SLAM) have been described as cellular receptors for certain MV strains. We found that human umbilical vein and brain microvascular endothelial cells (HUVECs and HBMECs) were CD46-positive, but did not express SLAM. Wild-type MV strains, which do not use CD46 as a receptor at the surface of transfected Chinese hamster ovary cells, infected HUVECs and HBMECs to varying extents in a strain-dependent way. This infection was not inhibited by antibodies to CD46. These data suggest the presence of an additional unidentified receptor for MV uptake and spread in human endothelial cells. INTRODUCTIONAfter acute infection of the upper respiratory tract, measles virus (MV) is rapidly transported to draining lymph nodes forming giant cells in the reticulo-endothelial system. MV then establishes a systemic infection and spreads to different organs, including the skin. In these organs, virus replicates primarily in endothelial cells (ECs), epithelial cells and monocytes/macrophages (Griffin & Bellini, 1996). ECs of dermal capillaries (Kimura et al., 1975) and small vessels throughout the body show clear evidence of MV infection. This appears to play a central role in pathogenesis, leading to changes in the skin, conjunctivae, mucous membranes and the brain (Cosby & Brankin, 1995), accompanied by vascular dilatation, increased vascular permeability, mononuclear cell infiltration and infection of surrounding tissues. In rare cases, the EC infection may extend to a severe haemorrhagic infection with confluent haemorrhagic skin eruptions and intravascular coagulopathy, so-called haemorrhagic or black measles. Brain ECs and capillary endothelium of lymph nodes and the thymus have been found to be infected in fatal cases of acute measles (Esolen et al., 1995; Moench et al., 1988). In subacute sclerosing panencephalitis (SSPE) patients, brain ECs appear to be infected in addition to various neural cells (Allen et al., 1996;Isaacson et al., 1996;Kirk et al., 1991).Following the identification of CD46 as a receptor for MV vaccine and laboratory strains (Dörig et al., 1993;Naniche et al., 1993a), evidence has accumulated that many wildtype isolates do not use CD46 as a receptor. Recently, the signalling lymphocytic activation molecule (SLAM, CD150) has been identified as a common receptor interacting with MV vaccine as well as wild-type strains (Erlenhoefer et al., 2001(Erlenhoefer et al., , 2002Hsu et al., 2001; Ono et al., 2001a, b;Tatsuo et al., 2000). SLAM is expressed on human B cell lines, primary activated B and T cells, memory cells and activated monocytes and monocyte-derived dendritic cells (Cocks et al., 1995;Minagawa et al., 2001;Ohgimoto et al., 2001;Polacino et al., 1996;Punnonen et al., 1997), and its usage as a receptor c...

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“…Immature DCs express high levels of both DC-SIGN and CD46 and low levels of CD150 (Fig. 5A) (27,31). The interactions of different MV strains with immature DCs were investigated using blocking antibodies against the different receptors to determine their contributions.…”

Section: Dc-sign Interacts With MV Glycoproteins F and Hmentioning

confidence: 99%

Measles Virus Targets DC-SIGN To Enhance Dendritic Cell Infection

Witte

Abt

Schneider‐Schaulies

et al. 2006

J Virol

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134

119

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Measles virus (MV) is a highly contagious human pathogen and remains a leading cause of childhood mortality in developing countries (28). The high mortality rate is associated with transient immune suppression during and after acute MV infection (5, 7). Dendritic cells (DCs) are thought to play a pivotal role in the pathogenesis of MV infection and to be involved in the immunosuppressive effects during and after acute MV infection (35, 39). Different mechanisms for MV interference with DC function have been described. In transgenic mice, MV infection inhibits DC development and expansion through type I interferon/ STAT2-specific signaling (20). In vitro, MV inhibits CD40 liganddependent DC maturation (38), and MV-infected DCs fail to stimulate proliferation and actively suppress T-cell proliferation (13,19,21,36,40). MV infection of plasmacytoid DCs interferes with Toll-like receptor-dependent IFN production (33). Moreover, MV infection of DC-T-cell cocultures induces Fas-mediated DC apoptosis (37).DCs are abundantly present in the tracheal epithelium, where MV enters the body, and therefore can be responsible for the transport of MV to lymphoid organs and subsequent transmission to T cells (13), similar to the role of DCs in human immunodeficiency virus type 1 (HIV-1) transmission (6). Since the interaction of MV with DCs can be important for both viral dissemination and modulation of T-cell responses, it is important to identify the different MV-specific receptors on DCs, their viral ligands, and the relative contributions of these interactions to MV uptake and spread.The known receptors for the MV hemagglutinin (H) protein are the complement receptor CD46 and the signaling lymphocyte activation molecule (SLAM/CD150). CD46 is present on all human nucleated cells; however, it is almost exclusively used by attenuated MV strains (2,10,24,29). CD150 is expressed by thymocytes, activated B cells, T cells, monocytes, and DCs and mediates the entry of all MV strains (12,42). Recent studies have demonstrated that several pathogens target the DC-specific Ctype lectin DC-SIGN for their dissemination or to modulate DC functions to facilitate their survival (15). DC-SIGN has a high affinity for mannose-containing carbohydrates expressed by viral glycoproteins (25). DC-SIGN binds various viruses, including the HIV envelope glycoprotein gp120, and can thereby enhance HIV-1 infection of T cells in trans (17). Here we have identified DC-SIGN as a novel receptor for MV. Immature DCs interact strongly with MV through both DC-SIGN and CD150. Both viral attachment and infection of immature DCs with MV strongly depend on DC-SIGN. However, DC-SIGN is not an entry receptor, since it does not mediate the entry of MV in DC-SIGNtransfected cell lines. Our data demonstrate that MV uses a twostep mechanism to infect immature DCs: MV targets DC-SIGN to interact with the MV receptors on immature DCs, which mediate the direct infection of DCs. Thus, DC-SIGN functions as an attachment receptor for MV, which is crucial for DC infection. MATER...

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The haemagglutinin protein is an important determinant of measles virus tropism for dendritic cells in vitro

Cited by 56 publications

References 41 publications

Gene expression patterns in dendritic cells infected with measles virus compared with other pathogens

Gene expression patterns in dendritic cells infected with measles virus compared with other pathogens

CD46- and CD150-independent endothelial cell infection with wild-type measles viruses

Measles Virus Targets DC-SIGN To Enhance Dendritic Cell Infection

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