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Clinical isolates of measles virus use CD46 as a cellular receptor
M Manchester1, D S Eto, A Valsamakis
1Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037, USA. marim@scripps.edu
Abstract:
Laboratory strains of measles viruses (MV), such as Edmonston and Halle, use the complement regulatory protein CD46 as a cell surface receptor. The receptor usage of clinical isolates of MV, however, remains unclear. Receptor usage by primary patient isolates of MV was compared to isolates that had been passaged on a variety of tissue culture cell lines. All of the isolates could infect cells in a CD46-dependent manner, but their tropism was restricted according to cell type (e.g., lymphocytes versus fibroblasts). The results indicate that patient isolates that have not been adapted to tissue culture cell lines use CD46 as a receptor. In addition, passaging primary MV patient isolates in B95-8 cells selected variants that had alternate receptor usage compared to the original isolate. Thus, changes in receptor usage by MV are dependent upon the cell type used for isolation. Furthermore, our results confirm the relevance of the CD46 receptor to natural measles infection.
Insights
Measles virus (MV) clinical isolates primarily use CD46 as a receptor, though cell type influences tropism. Adaptation to cell culture can alter MV receptor usage, highlighting CD46
Area of Science:
- Virology
- Immunology
Background:
- Laboratory measles virus (MV) strains utilize CD46 as a cellular receptor.
- Receptor usage by clinical MV isolates is not well-understood.
Purpose of the Study:
- To investigate the cell surface receptor usage of primary measles virus patient isolates.
- To compare receptor usage between MV isolates adapted to cell culture and those directly from patients.
Main Methods:
- Primary MV patient isolates were analyzed for receptor usage.
- Isolates were passaged on various tissue culture cell lines to assess adaptation.
- Tropism was evaluated across different cell types, including lymphocytes and fibroblasts.
Main Results:
- All MV isolates demonstrated CD46-dependent infection.
- Cell type significantly restricted MV tropism.
- Unadapted patient isolates consistently used CD46.
- Passaging in B95-8 cells selected for altered receptor usage.
Conclusions:
- Primary measles virus isolates utilize CD46 as their cellular receptor.
- Measles virus tropism is cell-type dependent and influenced by adaptation to cell culture.
- CD46 is confirmed as a relevant receptor for natural measles virus infection.