Molecular Characterization of Epitopes on the Measles Virus Hemagglutinin Protein

Hu, Aizhong; Sheshberadaran, Hooshmand; Norrby, Erling; Kövamees, Jan

doi:10.1006/viro.1993.1042

Cited by 54 publications

(69 citation statements)

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“…The complex-type sugars confer conformational and chemical variability on these sites, suppressing their potential antigenicity, and only unshielded side areas of MV-H are allowed to interact with antibodies. Epitopes of anti-MV-H antibodies (19)(20)(21) seem to be located in unshielded areas of MV-H (Fig. 2), supporting this notion.…”

Section: Resultssupporting

confidence: 60%

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Crystal structure of measles virus hemagglutinin provides insight into effective vaccines

Hanabusa¹,

Kajikawa

Maita

et al. 2007

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

225

260

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Measles still remains a major cause of childhood morbidity and mortality worldwide. Measles virus (MV) vaccines are highly successful, but the mechanism underlying their efficacy has been unclear. Here we report the crystal structure of the MV attachment protein, hemagglutinin, responsible for MV entry. The receptorbinding head domain exhibits a cubic-shaped ␤-propeller structure and forms a homodimer. N-linked sugars appear to mask the broad regions and cause the two molecules forming the dimer to tilt oppositely toward the horizontal plane. Accordingly, residues of the putative receptor-binding site, highly conserved among MV strains, are strategically positioned in the unshielded area of the protein. These conserved residues also serve as epitopes for neutralizing antibodies, ensuring the serological monotype, a basis for effective MV vaccines. Our findings suggest that sugar moieties in the MV hemagglutinin critically modulate virus-receptor interaction as well as antiviral antibody responses, differently from sugars of the HIV gp120, which allow for immune evasion.x-ray crystallography paramyxovirus ͉ morbillivirus ͉ SLAM ͉ infectious disease ͉ paramyxovirus

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Section: Resultssupporting

confidence: 60%

“…Importantly, the SLAMbinding site includes the reported epitopes of neutralizing antibodies. Escape mutants from mAb 55 that neutralizes the SLAM-dependent MV infection had an R533G substitution (23), whereas those from I-41 that blocks MV-H binding to SLAM had an F552V substitution (14,20) (Fig. 2).…”

Section: Resultsmentioning

confidence: 99%

Crystal structure of measles virus hemagglutinin provides insight into effective vaccines

Hanabusa¹,

Kajikawa

Maita

et al. 2007

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

225

260

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“…To identify residues in H protein required for EpR-dependent fusion support, we used an iterative mutagenesis protocol and assays measuring EpR-or SLAM-dependent fusion. Based on analyses of the H protein residues or epitopes available for interaction (16,(22)(23)(24), we focused mutagenesis on amino acids 382-617. We hypothesized that the EpR interaction is conserved within viruses of the Morbillivirus genus, as is the case for SLAM binding, and therefore mutated all the H protein amino acids conserved among the 3 morbilliviruses: MV, rinderpest virus (RV), and canine distemper virus (CDV) (Figure 2A).…”

Section: Infects Human Epithelial Cells Independently Of Slammentioning

confidence: 99%

Measles virus blind to its epithelial cell receptor remains virulent in rhesus monkeys but cannot cross the airway epithelium and is not shed

et al. 2008

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The current model of measles virus (MV) pathogenesis implies that apical infection of airway epithelial cells precedes systemic spread. An alternative model suggests that primarily infected lymphatic cells carry MV to the basolateral surface of epithelial cells, supporting MV shedding into the airway lumen and contagion. This model predicts that a mutant MV, unable to enter cells through the unidentified epithelial cell receptor (EpR), would remain virulent but not be shed. To test this model, we identified residues of the MV attachment protein sustaining EpR-mediated cell fusion. These nonpolar or uncharged polar residues defined an area located near the binding site of the signaling lymphocytic activation molecule (SLAM), the receptor for MV on lymphatic cells. We then generated an EpR-blind virus maintaining SLAM-dependent cell entry and inoculated rhesus monkeys intranasally. Hosts infected with the selectively EpR-blind MV developed rash and anorexia while averaging slightly lower viremia than hosts infected with wild-type MV but did not shed virus in the airways. The mechanism restricting shedding was characterized using primary well-differentiated human airway epithelial cells. Wild-type MV infected columnar epithelial cells bearing tight junctions only when applied basolaterally, while the EpR-blind virus did not infect these cells. Thus, EpR is probably a basolateral protein, and infection of the airway epithelium is not essential for systemic spread and virulence of MV.

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“…Cells were labeled 1 day posttransfection with 35 S-Met (75 Ci/ml) and 35 S-Cys (25 Ci/ml) in minimum essential medium and incubated at 37°C for 3 days. Supernatants were collected, clarified by centrifugation, and divided into identical aliquots for immunoprecipitation with purified monoclonal antibodies anti-HA or anti-MVH at 2 g/ml concentration and protein A-Sepharose (Amersham Biosciences).…”

Section: Immunoprecipitation Of Soluble Mvh Variantsmentioning

confidence: 99%

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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Molecular Characterization of Epitopes on the Measles Virus Hemagglutinin Protein

Cited by 54 publications

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Crystal structure of measles virus hemagglutinin provides insight into effective vaccines

Crystal structure of measles virus hemagglutinin provides insight into effective vaccines

Measles virus blind to its epithelial cell receptor remains virulent in rhesus monkeys but cannot cross the airway epithelium and is not shed

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

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