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Cotton rat (Sigmodon hispidus) signaling lymphocyte activation molecule (CD150) is an entry receptor for measles
Thomas Carsillo1, Devra Huey1, Amy Levinsky1
1Department of Veterinary Biosciences and Center for Microbial Interface Biology, The Ohio State University, Columbus, Ohio, United States of America.
Abstract:
Cotton rats (Sigmodon hispidus) replicate measles virus (MV) after intranasal infection in the respiratory tract and lymphoid tissue. We have cloned the cotton rat signaling lymphocytic activation molecule (CD150, SLAM) in order to investigate its role as a potential receptor for MV. Cotton rat CD150 displays 58% and 78% amino acid homology with human and mouse CD150, respectively. By staining with a newly generated cotton rat CD150 specific monoclonal antibody expression of CD150 was confirmed in cotton rat lymphoid cells and in tissues with a pattern of expression similar to mouse and humans. Previously, binding of MV hemagglutinin has been shown to be dependent on amino acids 60, 61 and 63 in the V region of CD150. The human molecule contains isoleucine, histidine and valine at these positions and binds to MV-H whereas the mouse molecule contains valine, arginine and leucine and does not function as a receptor for MV. In the cotton rat molecule, amino acids 61 and 63 are identical with the mouse molecule and amino acid 60 with the human molecule. After transfection with cotton rat CD150 HEK 293 T cells became susceptible to infection with single cycle VSV pseudotype virus expressing wild type MV glycoproteins and with a MV wildtype virus. After infection, cells expressing cotton rat CD150 replicated virus to lower levels than cells expressing the human molecule and formed smaller plaques. These data might explain why the cotton rat is a semipermissive model for measles virus infection.
Insights
Cotton rats replicate measles virus (MV) due to their CD150 protein, a potential MV receptor. Variations in cotton rat CD150 amino acids explain its semipermissive role in MV infection models.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Cotton rats (Sigmodon hispidus) are a model for measles virus (MV) replication in respiratory and lymphoid tissues.
- The signaling lymphocytic activation molecule (CD150, SLAM) is a known receptor for MV.
- Understanding the role of cotton rat CD150 in MV infection is crucial for this animal model.
Purpose of the Study:
- To clone and characterize cotton rat CD150.
- To investigate cotton rat CD150's function as a potential measles virus receptor.
- To elucidate the molecular basis for cotton rat semi-permissiveness to MV.
Main Methods:
- Cloning of cotton rat CD150 (SLAM).
- Expression analysis using a specific monoclonal antibody.
- Functional assays involving HEK 293 T cell transfection and MV infection.
- Comparison of amino acid sequences between human, mouse, and cotton rat CD150.
Main Results:
- Cotton rat CD150 shares significant homology with human and mouse CD150.
- CD150 expression was confirmed in cotton rat lymphoid cells and tissues.
- Transfected cells expressing cotton rat CD150 supported MV infection, albeit at lower levels than human CD150.
- Specific amino acid residues at positions 60, 61, and 63 in cotton rat CD150 differ from mouse and human CD150.
Conclusions:
- Cotton rat CD150 functions as a measles virus receptor.
- Amino acid differences in cotton rat CD150 contribute to its semi-permissive role in MV infection.
- These findings provide molecular insights into the cotton rat as an MV model.
