Octamerization Enables Soluble CD46 Receptor To Neutralize Measles Virus In Vitro and In Vivo

Christiansen, Dale; Devaux, Patricia; Réveil, Brigitte; Evlashev, Alexey; Horvat, Branka; Lamy, Jean; Rabourdin–Combe, Chantal; Cohen, Jacques H. M.; Gerlier, Denis

doi:10.1128/jvi.74.10.4672-4678.2000

Cited by 45 publications

(44 citation statements)

References 44 publications

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“…We also performed competition experiments using monomeric soluble CD46, but even at a high concentration, competition was not observed. This is in agreement with previous studies documenting that oligomerization of CD46 is necessary to sustain MV neutralization (43). The Y543A mutation strongly reduces H binding to nectin-4 and CD46 while leaving SLAM binding unaffected.…”

Section: Competition Between Nectin-4-and Cd46-dependent Entrysupporting

confidence: 82%

The Measles Virus Hemagglutinin β-Propeller Head β4-β5 Hydrophobic Groove Governs Functional Interactions with Nectin-4 and CD46 but Not Those with the Signaling Lymphocytic Activation Molecule

Mateo

Navaratnarajah

Syed

et al. 2013

J Virol

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Measles virus (MV), which belongs to the family Paramyxoviridae within the order Mononegavirales (1), may be the most contagious aerosol-transmitted virus circulating in human populations (2). In 2010, about 139,000 people died from secondary infections due to MV-induced immune suppression (3, 4). While a worldwide vaccination campaign aiming at eradication is ongoing (5), diminishing vaccine coverage in the United States and Europe has caused a rebound of measles cases in 2011, threatening the feasibility of eradication by 2020 (6).MV infection starts in alveolar macrophages and dendritic cells of the airways, which transport the virus to the lymphoid organs (7,8). MV then replicates rapidly and extensively in local lymph nodes and primary lymphatic organs. Infected immune cells circulate through the body and can transmit the infection to the respiratory epithelium, from where the virus is shed through coughing and sneezing (9-12).Wild-type MV sequentially infects immune cells through the signaling lymphocytic activation molecule (SLAM; CD150) (13) and epithelial cells through the adherens junction protein nectin-4, also known as poliovirus receptor-like 4 (PVRL4) (12,14,15). In addition, the MV vaccine strain uses the ubiquitous regulator of complement activation membrane cofactor protein (MCP; CD46) as a receptor (16,17). MV attachment to its three receptors occurs through hemagglutinin (H), a type II transmembrane glycoprotein (18). The H ectodomain is composed of a tetrameric membrane-proximal stalk topped by four six-bladed ␤-propeller globular heads (19). Receptor attachment to the H globular head can trigger refolding of the trimeric fusion (F) protein and cell entry.While H-to-F signal transmission is only beginning to be understood (20-24), the molecular basis of the interactions of the receptors with H is better characterized. Initial functional analyses identified different H residues important for the interactions with the three receptors (11,(25)(26)(27)(28)(29)(30)(31). These studies were recently complemented by crystal structures of H in complex with CD46, SLAM, and nectin-4 (32-34). The SLAM (32) and CD46 (33) costructures are based on slightly different vaccine lineage H proteins, while the nectin-4 costructure (34) is based on a wild-type H protein differing by more than 17 residues from the other two proteins. Comparative analyses of the three costructures (34) concluded that a hydrophobic pocket centered in the ␤4-␤5 groove is involved in binding of all receptors. On the other hand, previous functional analyses revealed differences between the interactions of H and individual receptors (11,(25)(26)(27)(28)(29)(30)(31). Based on the recent identification of nectin-4 as an epithelial receptor, based on the availability of new cell lines and specific reagents for all three receptors, and focusing on the overlap of the structural footprints of the receptors, we reexamined here the functional interactions of H with its three cellular partners. We used a vaccine lineage H protein, allowing direct...

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Section: Competition Between Nectin-4-and Cd46-dependent Entrysupporting

confidence: 82%

The Measles Virus Hemagglutinin β-Propeller Head β4-β5 Hydrophobic Groove Governs Functional Interactions with Nectin-4 and CD46 but Not Those with the Signaling Lymphocytic Activation Molecule

Mateo

Navaratnarajah

Syed

et al. 2013

J Virol

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“…The affinities for CD46 binding to dimeric (MVH3) or monomeric (MVH4) proteins determined from either the kinetic constants (K D ) or the MVH-bound receptor at steady-state conditions (K D * ) were not significantly different. CD46 binding affinity was similar to that reported (120 nM) for monomeric receptor binding to membrane bound MVH (26). The kinetic association constants (k a ) for binding of both CD46 and SLAM to the MVH3 variant were slightly higher, although the k d rates were almost identical.…”

Section: Affinity and Kinetics For Binding Of Monomeric Solublesupporting

confidence: 56%

Distinct Kinetics for Binding of the CD46 and SLAM Receptors to Overlapping Sites in the Measles Virus Hemagglutinin Protein

Santiago¹,

Björling²,

Stehle³

et al. 2002

Journal of Biological Chemistry

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“…3), suggesting that cross-linked CD46ex-huFc mimics the multiple-interaction situation when the virus contacts the cell surface. Similarly, CD46 cross-linking by genetically fusing the CD46 ectodomain to the octamer oligomerization domain of C4b binding protein resulted in a 2-log-enhanced MV-neutralizing activity in vitro and in vivo due to enhanced virus binding (8). These data suggest that the receptor density is of key importance not only for interaction of CD46 with trimeric FK but also for the multivalent virus particle.…”

Section: Discussionmentioning

confidence: 64%

Avidity Binding of Human Adenovirus Serotypes 3 and 7 to the Membrane Cofactor CD46 Triggers Infection

Trinh

Lesage

Chennamparampil

et al. 2012

J Virol

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The species B human adenoviruses (HAdVs) infect cells upon attaching to CD46 or desmoglein 2 (DSG-2) by one or several of their 12 fiber knob trimers (FKs). To test whether DSG-2 and CD46 simultaneously serve as virus receptors for adenovirus type 3 (Ad3), we performed individual and combined CD46/DSG-2 loss-of-function studies in human lung A549 and 16HBE14o cells. Our results suggest that in these cells, DSG-2 functions as a major attachment receptor for Ad3, whereas CD46 exerts a minor contribution to virus attachment and uptake in the range of ϳ10%. However, in other cells the role of CD46 may be more pronounced depending on, e.g., the expression levels of the receptors. To test if avidity allows Ad3/7 to use CD46 as a receptor, we performed gain-of-function studies. The cell surface levels of ectopically expressed CD46 in CHO or human M010119 melanoma cells lacking DSG-2 positively correlated with Ad3/7 infections, while Ad11/35 infections depended on CD46 but less on CD46 levels. Antibody-cross-linked soluble CD46 blocked Ad3/7/11/35 infections, while soluble CD46 alone blocked Ad11/35 but not Ad3/7. Soluble Ad3/7-FKs poorly inhibited Ad3/7 infection of CHO-CD46 cells, illustrating that Ad3/7-FKs bind with low affinity to CD46. This was confirmed by Biacore studies. Ad3/7-FK binding to immobilized CD46 at low density was not detected, unlike that of Ad11/35-FK. At higher CD46 densities, however, Ad3/7-FK bound to CD46 with only 15-fold-higher dissociation constants than those of Ad11/35-FK. These data show that an avidity mechanism for Ad3/7 binding to CD46 leads to infection of CD46-positive cells.

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Octamerization Enables Soluble CD46 Receptor To Neutralize Measles Virus In Vitro and In Vivo

Cited by 45 publications

References 44 publications

The Measles Virus Hemagglutinin β-Propeller Head β4-β5 Hydrophobic Groove Governs Functional Interactions with Nectin-4 and CD46 but Not Those with the Signaling Lymphocytic Activation Molecule

The Measles Virus Hemagglutinin β-Propeller Head β4-β5 Hydrophobic Groove Governs Functional Interactions with Nectin-4 and CD46 but Not Those with the Signaling Lymphocytic Activation Molecule

Distinct Kinetics for Binding of the CD46 and SLAM Receptors to Overlapping Sites in the Measles Virus Hemagglutinin Protein

Avidity Binding of Human Adenovirus Serotypes 3 and 7 to the Membrane Cofactor CD46 Triggers Infection

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