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Multiple isoforms of CD46 (membrane cofactor protein) serve as receptors for measles virus
M Manchester1, M K Liszewski, J P Atkinson
1Department of Neuropharmacology, Scripps Research Institute, La Jolla, CA 92037.
Abstract:
Measles virus (MV) causes a productive infection in humans and certain simian hosts. Rodent cells such as Chinese hamster ovary (CHO) and murine cell lines normally resist MV infection. Human CD46, or membrane cofactor protein, a complement regulatory protein, recently has been reported as the cellular receptor for MV. Multiple isoforms of the CD46 protein exist; four of these isoforms are commonly expressed on human cells. Expression of each of the four isoforms in CHO cells followed by exposure to MV led to the appearance of viral proteins within the cells and on the cell surface as detected by immunofluorescence. Syncytium formation also was observed in the cultures. CHO cells expressing any of the four isoforms and exposed to MV formed infectious centers when plated on Vero cell monolayers, indicating that the cells can transmit virus to uninfected cells. The murine cell line MC57 expressing the BC1 isoform of CD46 also stained positively for MV antigens and was positive in the infectious center assay after exposure to MV. Treatment of CD46-expressing cells with antibody to human CD46 inhibited MV binding in a dose-dependent manner. These observations indicate that any of the four primary isoforms of CD46 are able to serve as a receptor for MV.
Insights
Measles virus (MV) can infect rodent cells if they express human CD46. All four common CD46 isoforms enable MV infection and transmission, demonstrating their role as cellular receptors.
Area of Science:
- Virology
- Cell Biology
- Immunology
Background:
- Measles virus (MV) infects humans and primates but typically not rodents.
- Human CD46 (membrane cofactor protein) is a known cellular receptor for MV.
- Rodent cells like CHO and murine lines resist MV infection.
Purpose of the Study:
- To investigate if different human CD46 isoforms can mediate MV infection in resistant rodent cells.
- To confirm the role of CD46 isoforms as functional receptors for MV.
Main Methods:
- Transfected Chinese hamster ovary (CHO) and murine MC57 cells with human CD46 isoforms.
- Exposed engineered cells to MV and assessed viral protein expression via immunofluorescence.
- Evaluated syncytium formation and infectious center formation.
- Tested the effect of anti-CD46 antibodies on MV binding.
Main Results:
- CHO cells expressing any of the four common CD46 isoforms supported MV infection, showing viral proteins intracellularly and on the cell surface.
- Engineered cells formed syncytia and infectious centers, indicating viral transmission capability.
- Murine MC57 cells expressing CD46 isoform BC1 also supported MV infection and transmission.
- Antibody treatment inhibited MV binding to CD46-expressing cells in a dose-dependent manner.
Conclusions:
- All four common human CD46 isoforms can function as cellular receptors for Measles virus.
- CD46 expression confers susceptibility to MV infection in normally resistant rodent cell lines.
- These findings highlight the crucial role of CD46 in mediating MV cellular entry and spread.