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Published on: November 1, 2011
CD46 expression does not overcome the intracellular block of measles virus replication in transgenic rats
S Niewiesk1, J Schneider-Schaulies, H Ohnimus
1Institut für Virologie und Immunbiologie, Universität Würzburg, Germany.
Abstract:
The study of measles pathogenesis and the testing of improved vaccine candidates is hampered by the lack of a small animal model which is susceptible to infection by the intranasal route. With the identification of CD46 as a measles virus (MV) receptor, it was feasible to generate transgenic rats to overcome this problem. Although there was widespread expression of CD46 in the transgenic Sprague-Dawley rats, no measles-like disease could be induced after various routes of infection. The expressed transgenic protein was functionally intact since it mediated MV fusion and was downregulated by contact with MV hemagglutinin. In vitro studies revealed that CD46-expressing rat fibroblasts take up MV but do not allow viral replication, which explains the nonpermissiveness of the transgenic rats for in vivo infection.
Insights
Researchers developed transgenic rats expressing the measles virus (MV) receptor CD46 to model measles pathogenesis. However, these rats did not develop measles-like disease, limiting their use for vaccine testing.
Area of Science:
- Virology
- Immunology
- Genetics
Background:
- Studying measles pathogenesis and developing vaccines is challenging due to the absence of a suitable small animal model for intranasal infection.
- The identification of CD46 as a measles virus (MV) receptor provided a potential avenue for creating such a model.
Purpose of the Study:
- To generate and evaluate transgenic Sprague-Dawley rats expressing human CD46 as a model for measles virus infection.
- To assess the susceptibility of these rats to measles-like disease following various infection routes.
Main Methods:
- Generation of transgenic Sprague-Dawley rats expressing the CD46 measles virus receptor.
- Infection of transgenic rats via multiple routes to assess disease induction.
- In vitro studies using CD46-expressing rat fibroblasts to evaluate measles virus uptake and replication.
Main Results:
- Transgenic rats exhibited widespread CD46 expression, which was functionally intact and mediated MV fusion.
- Despite CD46 expression and interaction with MV hemagglutinin, no measles-like disease was observed in the infected transgenic rats.
- In vitro, CD46-expressing rat fibroblasts internalized MV but did not support viral replication.
Conclusions:
- Transgenic rats expressing CD46 are not permissive to measles virus infection in vivo, despite functional receptor expression.
- The lack of viral replication in CD46-expressing rat fibroblasts explains the non-permissiveness of the transgenic rat model.
- This model is unsuitable for studying measles pathogenesis or testing vaccine candidates via intranasal infection routes.
