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CD44 is not required for poliovirus replication
1Department of Microbiology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
Abstract:
The identification of a monoclonal antibody, AF3, which recognizes a single isoform of the cell surface protein CD44 and preferentially blocks binding of serotype 2 poliovirus to HeLa cells, suggested that CD44 might be an accessory molecule to Pvr, the cell receptor for poliovirus, and that it could play a role in the function of the poliovirus receptor site. We show here that only AF3 blocks binding of serotype 2 poliovirus to HeLa cells and, in contrast to a previously published report, that the anti-CD44 monoclonal antibodies A3D8 and IM7 are unable to block binding of poliovirus. To determine whether CD44 is involved in poliovirus infection, we analyzed the replication of all three serotypes of poliovirus in human neuroblastoma cells which lack or express CD44 and in mouse neuroblastoma cells which lack Pgp-1, the mouse homolog of human CD44, and which express Pvr. All three poliovirus serotypes replicate with normal kinetics and to normal levels in the absence or presence of CD44 or in the absence of Pgp-1. Furthermore, the binding affinity constants of all three poliovirus serotypes for Pvr are unaffected by the presence or absence of CD44 in the human neuroblastoma cell line. We conclude that CD44 and Pgp-1 are not required for poliovirus replication and are unlikely to be involved in poliovirus pathogenesis.
Insights
The cell surface protein CD44 and its mouse homolog Pgp-1 are not essential for poliovirus replication. This study found no evidence that CD44 plays a role in poliovirus infection or pathogenesis.
Area of Science:
- Virology
- Cell Biology
- Immunology
Background:
- The cell surface protein CD44 was hypothesized to be an accessory molecule for poliovirus receptor (Pvr) based on antibody binding studies.
- Previous research suggested CD44 might influence poliovirus binding to cells.
Purpose of the Study:
- To investigate the role of CD44 in poliovirus infection and replication.
- To determine if CD44 is necessary for poliovirus binding and pathogenesis.
Main Methods:
- Utilized monoclonal antibodies to assess poliovirus binding to cells expressing CD44.
- Analyzed poliovirus replication in human and mouse neuroblastoma cells with varying CD44 and Pgp-1 expression levels.
- Measured binding affinity of poliovirus serotypes to Pvr in the presence or absence of CD44.
Main Results:
- Only antibody AF3, not A3D8 or IM7, blocked serotype 2 poliovirus binding.
- All three poliovirus serotypes replicated normally in cells lacking or expressing CD44, and in cells lacking Pgp-1.
- The presence or absence of CD44 did not affect the binding affinity of poliovirus serotypes to Pvr.
Conclusions:
- CD44 and its mouse homolog Pgp-1 are not required for poliovirus replication.
- CD44 is unlikely to be involved in poliovirus pathogenesis or serve as a crucial co-receptor for Pvr.