Role of CD46 in Measles Virus Infection in CD46 Transgenic Mice

Blixenkrone-Møller, Merete; Bernard, Arlette; Bencsik, Anna; Sixt, Nathalie; Le, Diamond; Js, Logan; Tf, Wild

doi:10.1006/viro.1998.9301

Cited by 56 publications

(30 citation statements)

References 35 publications

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“…We then performed a comparative examination of MCP (CD46) expression in the three independently derived strains. This comparison did not include a fourth strain generated using a 80-kb genomic fragment [38]. We found that MCP (CD46) was expressed on all cells and tissues analysed.…”

Section: Discussionmentioning

confidence: 96%

Membrane cofactor protein (MCP; CD46) expression in transgenic mice

Kemper

Leung

Stephensen

et al. 2001

Clinical and Experimental Immunology

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SUMMARYHuman membrane cofactor protein (MCP; CD46) is a widely distributed complement regulator. In the mouse, expression of MCP is largely restricted to the testis while a related, widely expressed protein (Crry) appears to perform MCP's (CD46) regulatory activity. We have developed two mouse strains transgenic for human MCP (CD46) utilizing an , 400 kb YAC clone carrying the complete gene. A third mouse strain was generated using an overlapping YAC clone isolated from a second library. The expression of human MCP (CD46) in these mouse strains was characterized by immunohistochemistry, FACS, Western blotting and RT-PCR. No differences were detected in the isoform pattern or distribution among the three strains, although the expression level varied according to how many copies of the gene were integrated. The expression profile closely mimicked that observed in humans, including the same pattern of isoform expression as the donor. In addition, tissue-specific isoform expression in the kidney, salivary gland and brain paralleled that observed in man. The transgenic mice expressed low levels of MCP (CD46) on their E, in contrast to humans but in line with most other primates. These mice should be a useful tool to analyse tissue-specific expression, to establish animal models of infections and to characterize the role of MCP (CD46) in reproduction.

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Section: Discussionmentioning

confidence: 96%

Membrane cofactor protein (MCP; CD46) expression in transgenic mice

Kemper

Leung

Stephensen

et al. 2001

Clinical and Experimental Immunology

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“…It should also have applications in the development of recombinant MV vaccines (19,20,31) and studying the oncolytic properties of this virus (21,22,32). Other groups have generated mice that express human CD46, which is the receptor used by vaccine and laboratory adapted strains of MV for virus entry (2)(3)(4)(5)(6)33). These labs reported transient MV infections in these mice with limited virus production due to the induction of innate immune responses.…”

Section: Discussionmentioning

confidence: 99%

Measles virus replication in lymphatic cells and organs of CD150 (SLAM) transgenic mice

Welstead

Iorio

Draker

et al. 2005

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

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A transgenic mouse containing the complete human SLAM (hSLAM͞CD150) gene, including its endogenous promoter for transcription, was generated by using human genomic DNA cloned into a bacterial artificial chromosome. hSLAM, the primary receptor for measles viruses (MV), was expressed on activated B, T, and dendritic cells with an expression profile equivalent to that of humans. We demonstrated that hSLAM ؉ cells obtained from the transgenic mouse, including activated B, T, and dendritic cells, were susceptible to MV infection in a receptor-dependent manner. Evidence was provided for transient infection in the nasal lymph nodes of hSLAM ؉ mice after intranasal inoculation. Virus was rapidly cleared without signs of secondary replication. To improve the efficiency of MV production, the hSLAM ؉ mice were bred with mice having a Stat1-deficient background. These mice were more susceptible to MV infection and produced more virus particles. After intranasal and intraperitoneal inoculation of these mice with MV, infections of the thymus, spleen, nasal, mesenteric, and leg lymph nodes were detected. Upon necropsy, enlarged lymph nodes and spleen were apparent. Flow cytometric analysis showed that abnormally large numbers of mature neutrophils and natural killer cells caused the splenomegaly. The hSLAM transgenic mouse constitutes an improved rodent model for studying the interaction of MV with immune cells that more accurately reflects the infection pattern found in humans.activated lymphocytes ͉ transgenic mouse ͉ dendritic cells M easles viruses (MV) is one of the most contagious diseases known to man and is a major killer of children in the developing countries of Africa and South America. The high mortality rate associated with MV infection results from increased susceptibility to opportunistic infections. Although MV has been studied extensively, the mechanism for the immunosuppressive effects observed during MV infection remains unclear (1).The development of a mouse model may lead to a better understanding of the immune suppression induced by MV. This was previously attempted by expressing CD46, one of the two receptors for MV, in mice (2-6). However, CD46 receptor, a ubiquitously expressed glycoprotein, is only used by vaccine or laboratory adapted strains of MV. Recently, a second receptor for MV was discovered: CD150 or signaling lymphocytic activation molecule (SLAM) (7-9). SLAM is a host cell receptor for both vaccine and WT MV strains of MV. It is a 70-kDa, type

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“…MIBE is observed in immunosupressed patients, for example, in some of those with human immunodeficiency virus type 1 infection and those undergoing immunosuppressive therapy. It has become more prevalent in recent years and leads to the death of the individual within a few weeks.Two approaches have been used to study MV neurotropism in efforts to generate a small-animal model for CNS infection.First, following the identification of the complement cofactor CD46 as a receptor for the Edmonston strain of MV (11, 30) a number of groups have produced transgenic animals which express the receptor (6,16,28,29,32,34). The inflammatory response in the CNS of transgenic animals has been investigated.…”

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confidence: 99%

“…First, following the identification of the complement cofactor CD46 as a receptor for the Edmonston strain of MV (11,30) a number of groups have produced transgenic animals which express the receptor (6,16,28,29,32,34). The inflammatory response in the CNS of transgenic animals has been investigated.…”

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confidence: 99%

In Vitro and In Vivo Infection of Neural Cells by a Recombinant Measles Virus Expressing Enhanced Green Fluorescent Protein

Duprex

McQuaid

Roscic-Mrkic

et al. 2000

J Virol

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This study focused on the in vitro infection of mouse and human neuroblastoma cells and the in vivo infection of the murine central nervous system with a recombinant measles virus. An undifferentiated mouse neuroblastoma cell line (TMN) was infected with the vaccine strain of measles virus (MVeGFP), which expresses enhanced green fluorescent protein (EGFP). MVeGFP infected the cells, and cell-to-cell spread was studied by virtue of the resulting EGFP autofluorescence, using real-time confocal microscopy. Cells were differentiated to a neuronal phenotype, and extended processes, which interconnected the cells, were observed. It was also possible to infect the differentiated neuroblastoma cells (dTMN) with MVeGFP. Single autofluorescent EGFP-positive cells were selected at the earliest possible point in the infection, and the spread of EGFP autofluorescence was monitored. In this instance the virus used the interconnecting processes to spread from cell to cell. Human neuroblastoma cells (SH-SY-5Y) were also infected with MVeGFP. The virus infected these cells, and existing processes were used to initiate new foci of infection at distinct regions of the monolayer. Transgenic animals expressing CD46, a measles virus receptor, and lacking interferon type 1 receptor gene were infected intracerebrally with MVeGFP. A productive infection ensued, and the mice exhibited clinical signs of infection, such as ataxia and an awkward gait, identical to those previously observed for the parental virus (Edtag). Mice were sacrificed, and brain sections were examined for EGFP autofluorescence by confocal scanning laser microscopy over a period of 6 h. EGFP was detected in discrete focal regions of the brain and in processes, which extended deep into the parenchyma. Collectively, these results indicate (i) that MVeGFP can be used to monitor virus replication sensitively, in real time, in animal tissues, (ii) that infection of ependymal cells and neuroblasts provides a route by which measles virus can enter the central nervous system in mouse models of encephalitis, and (iii) that upon infection, the virus spreads transneuronally.Measles virus (MV) infects over 40 million individuals each year. Encephalomyelitis can occur as part of the acute infection, while subacute sclerosing panencephalitis (SSPE) and measles inclusion body encephalitis (MIBE) are two rare sequelae of central nervous system (CNS) infections (1, 42). SSPE is invariably fatal and occurs an average of 8 years after the acute infection. There is no evidence to suggest that a variant virus is involved in the primary infection, nor has any vaccine virus has been implicated in the establishment of SSPE. The virus appears to persist in the body at an unknown site (37). In SSPE, CNS infection develops in the presence of high titers of antiviral antibodies, and the isolated viruses are defective in budding (12). Mutations accumulate in the virus genome, especially in the fusion and matrix genes, and transcription of envelope genes is reduced by an altered transcription gra...

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Role of CD46 in Measles Virus Infection in CD46 Transgenic Mice

Cited by 56 publications

References 35 publications

Membrane cofactor protein (MCP; CD46) expression in transgenic mice

Membrane cofactor protein (MCP; CD46) expression in transgenic mice

Measles virus replication in lymphatic cells and organs of CD150 (SLAM) transgenic mice

In Vitro and In Vivo Infection of Neural Cells by a Recombinant Measles Virus Expressing Enhanced Green Fluorescent Protein

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