High Pathogenicity of Wild-Type Measles Virus Infection in CD150 (SLAM) Transgenic Mice

Sellin, Caroline I.; Davoust, Nathalie; Guillaume, Vanessa; Baas, Dominique; Belin, Marie‐Françoise; Buckland, Robin; Wild, T. F.; Horvat, Branka

doi:10.1128/jvi.00209-06

Cited by 38 publications

(56 citation statements)

References 53 publications

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“…CD46 transgenic mice (7, 20, 33, 39, 44), however, may not be suitable for the analysis of MV pathogenesis because CD46 acts as a receptor only for MV vaccine strains and not for most viruses in measles patients (40). Two groups produced SLAM transgenic mice using human SLAM cDNA driven by nonauthentic promoters and showed that MV could infect these mice (16,17,46). However, the expression profiles of SLAM are not natural in these mice.…”

Section: Discussionmentioning

confidence: 99%

Measles Virus Infection of SLAM (CD150) Knockin Mice Reproduces Tropism and Immunosuppression in Human Infection

Ohno¹,

Ono²,

Seki³

et al. 2007

J Virol

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The human signaling lymphocyte activation molecule (SLAM, also called CD150), a regulator of antigendriven T-cell responses and macrophage functions, acts as a cellular receptor for measles virus (MV), and its V domain is necessary and sufficient for receptor function. We report here the generation of SLAM knockin mice in which the V domain of mouse SLAM was replaced by that of human SLAM. The chimeric SLAM had an expected distribution and normal function in the knockin mice. Splenocytes from the SLAM knockin mice permitted the in vitro growth of a virulent MV strain but not that of the Edmonston vaccine strain. Unlike in vitro infection, MV could grow only in SLAM knockin mice that also lacked the type I interferon receptor (IFNAR). After intraperitoneal or intranasal inoculation, MV was detected in the spleen and lymph nodes throughout the body but not in the thymus. Notably, the virus appeared first in the mediastinal lymph node after intranasal inoculation. Splenocytes from MV-infected IFNAR ؊/؊ SLAM knockin mice showed suppression of proliferative responses to concanavalin A. Thus, MV infection of SLAM knockin mice reproduces lymphotropism and immunosuppression in human infection, serving as a useful small animal model for measles.

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Section: Discussionmentioning

confidence: 99%

Measles Virus Infection of SLAM (CD150) Knockin Mice Reproduces Tropism and Immunosuppression in Human Infection

Ohno¹,

Ono²,

Seki³

et al. 2007

J Virol

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“…The constructs for SLAM and nectin 4 were commercially acquired. Anti-MV hemagglutinin cl.55 neutralizing antibody, which blocks interaction between H and CD150, has been previously described (43)(44)(45).…”

Section: Plasmids and Reagentsmentioning

confidence: 99%

“…Sera were taken from infected mice at the end of the protocol by intracardiac puncture in EDTA Vacutainer tubes and tested for anti-MV antibodies by ELISA as previously described (45). Briefly, MV nucleoprotein obtained from baculovirus-infected insect cells and purified was coated onto 96-well ELISA plates overnight (1 g/well).…”

Section: Plasmids and Reagentsmentioning

confidence: 99%

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Prevention of Measles Virus Infection by Intranasal Delivery of Fusion Inhibitor Peptides

Mathieu

Huey

Jurgens

et al. 2015

J Virol

100

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Measles virus (MV) infection is undergoing resurgence and remains one of the leading causes of death among young children worldwide despite the availability of an effective measles vaccine. MV infects its target cells by coordinated action of the MV H and the fusion (F) envelope glycoprotein; upon receptor engagement by H, the prefusion F undergoes a structural transition, extending and inserting into the target cell membrane and then refolding into a postfusion structure that fuses the viral and cell membranes. By interfering with this structural transition of F, peptides derived from the heptad-repeat (HR) regions of F can potently inhibit MV infection at the entry stage. We show here that specific features of H's interaction with its receptors modulate the susceptibility of MV F to peptide fusion inhibitors. A higher concentration of inhibitory peptides is required to inhibit F-mediated fusion when H is engaged to its nectin-4 receptor than when H is engaged to its CD150 receptor. Peptide inhibition of F may be subverted by continued engagement of receptor by H, a finding that highlights the ongoing role of H-receptor interaction after F has been activated and that helps guide the design of more potent inhibitory peptides. Intranasal administration of these peptides results in peptide accumulation in the airway epithelium with minimal systemic levels of peptide and efficiently prevents MV infection in vivo in animal models. The results suggest an antiviral strategy for prophylaxis in vulnerable and/or immunocompromised hosts. IMPORTANCE Measles virus (MV) infection causes an acute illness that may be associated with infection of the central nervous system (CNS)and severe neurological disease. No specific treatment is available. We have shown that parenterally delivered fusion-inhibitory peptides protect mice from lethal CNS MV disease. Here we show, using established small-animal models of MV infection, that fusion-inhibitory peptides delivered intranasally provide effective prophylaxis against MV infection. Since the fusion inhibitors are stable at room temperature, this intranasal strategy is feasible even outside health care settings, could be used to protect individuals and communities in case of MV outbreaks, and could complement global efforts to control measles.

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“…Several transgenic or knock-in mice expressing human SLAM or CD46 have been generated as small animal models for measles (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). To facilitate MV replication, these mice usually have to be made defective in IFN signaling (16,(18)(19)(20) or used when they are newly born (15,17). Similarly, when human SLAM or CD46 is expressed by transfection, rodent cells become susceptible to MV, but do not allow MV growth as efficiently as primate cells (14,26).…”

mentioning

confidence: 99%

Expression of the Sendai (murine parainfluenza) virus C protein alleviates restriction of measles virus growth in mouse cells

Iwasaki

Yanagi

2011

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

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Measles virus (MV), a human pathogen, uses the signaling lymphocyte activation molecule (SLAM) or CD46 as an entry receptor. Although several transgenic mice expressing these receptors have been generated as small animal models for measles, these mice usually have to be made defective in IFN-α/β signaling to facilitate MV replication. Similarly, when functional receptors are expressed by transfection, mouse cells do not allow MV growth as efficiently as primate cells. In this study, we demonstrate that MV efficiently grows in SLAM-expressing mouse cells in which the Sendai virus (SeV) C protein is transiently expressed. We developed a SLAM-expressing mouse cell line whose genome also encodes the SeV C protein downstream of the sequence flanked with loxP sequences. When this cell line was infected with the recombinant MV expressing the Cre recombinase, the SeV C protein was readily expressed. Importantly, the Cre recombinase-encoding MV grew in this cell line much more efficiently than it did in the parental cell. The minigenome assay demonstrated that the SeV C protein does not modulate MV RNA synthesis. Analyses using the mutant proteins with the defined functional defects revealed that the IFN-antagonist function, but not the budding-accelerating function, of the SeV C protein was critical for supporting efficient MV growth in mouse cells. Our results indicate that insufficient IFN antagonism can be an important determinant of the host range of viruses, and the system described here may be useful to overcome the species barrier of other human viruses.

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High Pathogenicity of Wild-Type Measles Virus Infection in CD150 (SLAM) Transgenic Mice

Abstract: Measles virus (MV) infection causes an acute childhood disease, associated in certain cases

Cited by 38 publications

References 53 publications

Measles Virus Infection of SLAM (CD150) Knockin Mice Reproduces Tropism and Immunosuppression in Human Infection

Measles Virus Infection of SLAM (CD150) Knockin Mice Reproduces Tropism and Immunosuppression in Human Infection

Prevention of Measles Virus Infection by Intranasal Delivery of Fusion Inhibitor Peptides

Expression of the Sendai (murine parainfluenza) virus C protein alleviates restriction of measles virus growth in mouse cells

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