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Role of CD46 in measles virus infection in CD46 transgenic mice
M Blixenkrone-Møller1, A Bernard, A Bencsik
1Immunité et Vaccination, Ex-Bâtiment Institut Pasteur de Lyon, Avenue Tony Garnier, Lyon Cedex 07, 69365, France. MBM@KVL.DK
Abstract:
The susceptibility of CD46 (human membrane cofactor protein) transgenic mice to measles virus (MV) infection was investigated. Cell cultures (lung and kidney) established from transgenic and control mice showed that although both could be infected only those from the CD46+ mice gave fusion. A complete round of replication with the release of infectious virus was detected exclusively in the transgenic cell cultures whose permissiveness to MV was markedly less than that of Vero cells. The ability of MV to replicate in vivo in mice was studied using both vaccine and laboratory-adapted wild-type strains of virus. After intraperitoneal and intranasal inoculations of transgenic mice, virus replication could not be detected. In contrast intracerebral inoculation induced infection in both transgenic and nontransgenic mice. Our results from in vitro infection studies support the hypothesis that CD46 is a major host cell factor involved in the MV-induced fusion process and MV entry. The studies further indicate that MV tropism is not governed solely by the expression of the CD46 gene and that the high efficiency of the replicative cycles characteristic of fully permissive host cells requires additional factors, which are lacking in both transgenic and nontransgenic mice.
Insights
Transgenic mice expressing human CD46 (membrane cofactor protein) showed limited measles virus (MV) replication in vitro and none in vivo, suggesting CD46 is crucial but insufficient for efficient MV infection.
Area of Science:
- Virology
- Immunology
- Genetics
Background:
- Measles virus (MV) causes significant global health issues.
- Understanding MV host-pathogen interactions is key to developing effective interventions.
- CD46 (membrane cofactor protein) is a known cellular receptor for MV.
Purpose of the Study:
- To investigate the role of CD46 in MV infection using transgenic mice.
- To determine if CD46 expression alone confers permissiveness to MV.
- To explore factors influencing MV tropism and replication efficiency.
Main Methods:
- Generation of CD46 transgenic mice.
- In vitro infection of lung and kidney cell cultures from transgenic and control mice with MV.
- In vivo infection studies using vaccine and wild-type MV strains via intraperitoneal, intranasal, and intracerebral routes.
Main Results:
- CD46 transgenic cells exhibited MV-induced fusion and limited replication, but less efficiently than Vero cells.
- In vivo, MV replication was not detected after peripheral inoculation of transgenic mice.
- Intracerebral inoculation led to infection in both transgenic and nontransgenic mice, indicating CD46 is not the sole determinant of susceptibility.
Conclusions:
- CD46 is a significant host factor for MV entry and fusion.
- MV tropism and efficient replication depend on additional host factors beyond CD46 expression.
- Murine models have limitations for studying MV pathogenesis due to a lack of fully permissive factors.