Summary auto-generated
This study investigated why measles virus (MV) replicates poorly in transgenic mice expressing the human CD46 receptor compared to human cells. Researchers compared MV infection in human T lymphocytes and murine T lymphocytes from three transgenic mouse lines expressing different CD46 levels. While MV binding and entry correlated with CD46 expression levels, with the highest-expressing transgenic line (MCP-B) showing similar entry efficiency to human cells, viral replication remained substantially lower in all mouse lymphocytes. Human cells produced approximately 10-fold more infectious virus particles than transgenic mouse cells, along with higher levels of viral mRNA and protein expression. These results suggest that CD46 expression alone is insufficient for efficient MV replication in murine lymphocytes, and that unidentified intracellular factors operating after viral entry—such as differences in interferon response, viral budding efficiency, or required host cell proteins—restrict MV replication in mouse cells. The findings have important implications for developing transgenic mouse models of measles pathogenesis.
Key findings
- MV binding and entry into murine lymphocytes correlate with CD46 receptor expression levels, matching human cells in the highest-expressing transgenic line (MCP-B)
- Despite similar early infection steps, MV replication is at least 10-fold lower in murine transgenic lymphocytes compared to human lymphocytes, indicating post-entry restrictions
- Viral mRNA and protein production are significantly reduced in murine cells relative to human cells, even when CD46 expression is equivalent
- Species-specific intracellular factors limit MV replication in murine lymphocytes independent of CD46 receptor availability
- High CD46 expression alone is insufficient for creating an adequate transgenic mouse model of measles pathogenesis
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Abstract
Analysis of measles virus (MV) pathogenesis requires the development of an adequate small animal model of MV infection. In this study, permissivity to MV infection was compared in human and transgenic murine T lymphocytes, expressing different levels of the human MV receptor, CD46. Whereas MV binding and entry correlated with CD46 expression, higher levels of MV replication were always observed in human T lymphocytes. This suggests the existence of intracellular factors, acting posterior to virus entry, that could limit MV replication in murine lymphocytes and should be considered when creating new animal models of MV infection.