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Poliovirus host range is determined by a short amino acid sequence in neutralization antigenic site I
M G Murray1, J Bradley, X F Yang
1Department of Microbiology, School of Medicine, State University of New York, Stony Brook 11794.
Abstract:
The mouse-adapted strain of poliovirus type 2 (Lansing) induces fatal poliomyelitis in mice after intracerebral inoculation, whereas mice inoculated with poliovirus type 1 (Mahoney) show no signs of disease. Previous work indicated that the adaptation to mouse virulence is associated with the viral capsid proteins and that mutations in neutralization antigenic site I of poliovirus reduce neurovirulence of the Lansing strain in mice. The role of antigenic site I in mouse neurovirulence was further explored by constructing an antigenic hybrid virus. Six amino acids in antigenic site I of the Mahoney strain were replaced with a sequence specific for the Lansing strain by using a mutagenesis cartridge. The hybrid virus was neutralized by polyclonal antisera elicited by the type 1 and type 2 strains of poliovirus and by neutralizing monoclonal antibodies directed against antigenic site I of type 2 virus. The hybrid virus induced paralytic disease in mice, an observation demonstrating that a short sequence of amino acids in antigenic site I is an important determinant of poliovirus host range. Antigenic site I may be involved in attachment of poliovirus to cells of the mouse central nervous system.
Insights
Poliovirus type 2 (Lansing) causes fatal disease in mice, unlike poliovirus type 1 (Mahoney). A specific amino acid sequence in antigenic site I is crucial for poliovirus host range and mouse neurovirulence.
Area of Science:
- Virology
- Molecular Biology
- Immunology
Background:
- Poliovirus type 2 (Lansing strain) is neurovirulent in mice, while type 1 (Mahoney strain) is not.
- Previous studies linked viral capsid proteins and mutations in antigenic site I to reduced Lansing strain neurovirulence.
Purpose of the Study:
- To investigate the role of poliovirus antigenic site I in mouse neurovirulence.
- To construct and analyze an antigenic hybrid virus to understand host range determinants.
Main Methods:
- Site-directed mutagenesis was used to replace six amino acids in antigenic site I of the Mahoney strain with the Lansing strain sequence.
- The resulting hybrid virus was tested for neutralization by type-specific antisera and monoclonal antibodies.
- The neurovirulence of the hybrid virus was assessed in mice following intracerebral inoculation.
Main Results:
- The hybrid virus was neutralized by antibodies against both poliovirus type 1 and type 2.
- The hybrid virus induced paralytic disease in mice, similar to the Lansing strain.
- A short amino acid sequence in antigenic site I was identified as a key determinant of poliovirus host range.
Conclusions:
- Antigenic site I plays a critical role in determining poliovirus host range and mouse neurovirulence.
- This specific amino acid sequence may be involved in poliovirus attachment to mouse central nervous system cells.