Affiliation:
1. Department of Microbiology, College of Physicians & Surgeons, Columbia University, New York, New York 10032.
Abstract
The poliovirus P2/P712 strain is an attenuated virus that is closely related to the type 2 Sabin vaccine strain. By using a mouse model for poliomyelitis, sequences responsible for attenuation of the P2/P712 strain were previously mapped to the 5' noncoding region of the genome and a central region encoding VP1, 2Apro, 2B, and part of 2C. To identify specific determinants that attenuate the P2/P712 strain, recombinants between this virus and the mouse-adapted P2/Lansing were constructed and their neurovirulence in mice was determined. By using this approach, the attenuation determinant in the central region was mapped to capsid protein VP1. Candidate attenuating sequences in VP1 and the 5' noncoding region were identified by comparing the P2/P712 sequence with that of vaccine-associated isolate P2/P117, and the P2/117 sequences were introduced into the P2/Lansing-P2/P712 recombinants by site-directed mutagenesis. Results of neurovirulence assays in mice indicate that an A at nucleotide 481 in the 5' noncoding region and isoleucine (Ile) at position 143 of capsid protein VP1 are the major determinants of attenuation of P2/P712. These determinants also attenuated neurovirulence in transgenic mice expressing human poliovirus receptors, a new model for poliomyelitis in which virulent viruses are not host restricted. These results demonstrate that A-481 and Ile-143 are general determinants of attenuation.
Publisher
American Society for Microbiology
Subject
Virology,Insect Science,Immunology,Microbiology
Reference32 articles.
1. Agol V. 1990. Current approaches to the problem of poliovirus attenuation p. 311-318. In M. A. Brinton and F. X. Heinz (ed.) New aspects of positive-strand RNA viruses. American Society for Microbiology Washington D.C.
2. The attenuation of poliovirus neurovirulence. Annu;Almond J. W.;Rev. Microbiol.,1987
3. New poliovirus vaccines: a molecular approach;Almond J. W.;Vaccine,1984
4. Ausubel F. M. R. Brent R. E. Kingston D. D. Moore J. A. Smith J. G. Seidman and K. Struhl. 1987. Current protocols in molecular biology. John Wiley & Sons Inc. New York.
5. .Bouchard M. and V. R. Racaniello. Unpublished observations.
Cited by
160 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献