Reduced mouse neurovirulence of poliovirus type 2 Lansing antigenic variants selected with monoclonal antibodies.
The Lansing strain of poliovirus type 2 is a mouse-adapted virus that induces a fatal paralytic disease in mice after intracerebral inoculation. Our previous results indicated that the mouse-adapted phenotype maps to the Lansing viral capsid. To further define regions of the capsid that are specifically involved in the infection of mice, antigenic variants resistant to neutralization with monoclonal antibodies were selected, and their mouse neurovirulence was studied. The monoclonal antibodies used were directed against antigenic site 1, an immunodominant loop of capsid polypeptide VP1 located on the virion surface. Ten of twenty-two variants selected had lower intracerebral neurovirulence in mice when compared to the parental virus. Four of the ten antigenic variants with reduced neurovirulence were temperature sensitive (ts) for replication in HeLa cells, while the remaining six variants replicated in HeLa cells as well as the parent virus. Two ts+ variants that were studied had a reduced ability to replicate in the mouse brain. There was no difference in the histopathology and pattern of involvement in the central nervous system of one variant compared to the parent virus. In three variants, reduction of neurovirulence correlated with specific amino acid substitutions at positions 100 and 101 of VP1, located within antigenic site 1. The ts phenotype in three variants was associated with a single amino acid deletion at position 105. Virus recovered from the brain of paralyzed mice that had been inoculated with the antigenic variants was characterized to identify the virus causing disease. In most cases, brain isolates resembled the inoculated virus in neurovirulence and amino acid sequence at the antigenic site. Virus recovered from brains of paralyzed mice that had been inoculated with the ts variants was either ts+ or cold sensitive, and had become more neurovirulent. These results suggest that specific amino acid changes within an antigenic site on the virion surface may result in reduction of mouse neurovirulence without affecting viral replication in cultured cells.
La Monica
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N
Department of Microbiology, Columbia University of Physicians & Surgeons, New York, New York 10032.
Kupsky
W J
WJ
Racaniello
V R
VR
D000818:Animals; D000911:Antibodies, Monoclonal; D000940:Antigenic Variation; D000956:Antigens, Viral / Q000032:analysis; D001483:Base Sequence; D006367:HeLa Cells; D051379:Mice; D009420:Nervous System / Q000382:microbiology*; D009500:Neutralization Tests; D017955:Poliovirus / Q000276:immunology / Q000472:pathogenicity*; D013696:Temperature; D014779:Virus Replication
D000911:Antibodies, Monoclonal; D000956:Antigens, Viral