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Molecular evolution of a type 1 wild-vaccine poliovirus recombinant during widespread circulation in China
H M Liu1, D P Zheng, L B Zhang
1Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA. hdl1@cdc.gov
Abstract:
Type 1 wild-vaccine recombinant polioviruses were isolated from poliomyelitis patients in China from 1991 to 1993. We compared the sequences of 34 recombinant isolates over the 1,353-nucleotide (nt) genomic interval (nt 2480 to 3832) encoding the major capsid protein, VP1, and the protease, 2A. All recombinants had a 367-nt block of sequence (nt 3271 to 3637) derived from the Sabin 1 oral poliovirus vaccine strain spanning the 3'-terminal sequences of VP1 (115 nt) and the 5' half of 2A (252 nt). The remaining VP1 sequences were closely (up to 99.5%) related to those of a major genotype of wild type 1 poliovirus endemic to China up to 1994. In contrast, the non-vaccine-derived sequences at the 3' half of 2A were more distantly related (<90% nucleotide sequence match) to those of other contemporary wild polioviruses from China. The vaccine-derived sequences of the earliest (April 1991) isolates completely matched those of Sabin 1. Later isolates diverged from the early isolates primarily by accumulation of synonymous base substitutions (at a rate of approximately 3.7 x 10(-2) substitutions per synonymous site per year) over the entire VP1-2A interval. Distinct evolutionary lineages were found in different Chinese provinces. From the combined epidemiologic and evolutionary analyses, we propose that the recombinant virus arose during mixed infection of a single individual in northern China in early 1991 and that its progeny spread by multiple independent chains of transmission into some of the most populous areas of China within a year of the initiating infection.
Insights
Type 1 wild-vaccine recombinant polioviruses emerged in China, combining vaccine and wild virus genetic material. These viruses evolved rapidly, spreading across provinces within a year.
Area of Science:
- Virology
- Molecular Epidemiology
- Evolutionary Biology
Background:
- Poliomyelitis outbreaks in China (1991-1993) involved Type 1 wild-vaccine recombinant polioviruses.
- Understanding the genetic origins and evolution of these recombinants is crucial for public health.
Purpose of the Study:
- To analyze the genetic sequences of Type 1 wild-vaccine recombinant polioviruses isolated in China.
- To investigate the origins, evolutionary dynamics, and transmission patterns of these recombinant strains.
Main Methods:
- Comparative sequence analysis of the VP1 and 2A genomic regions (1,353 nucleotides) from 34 recombinant poliovirus isolates.
- Phylogenetic analysis to determine genetic relatedness to vaccine (Sabin 1) and wild poliovirus strains.
- Epidemiologic data integration to map transmission routes and timelines.
Main Results:
- All recombinants contained a 367-nucleotide segment from the Sabin 1 oral poliovirus vaccine strain.
- VP1 sequences were highly similar to endemic wild Type 1 poliovirus, while 3' 2A sequences showed distant relation to other wild strains.
- Accumulation of synonymous base substitutions indicated rapid evolution (3.7 x 10^-2 per site per year) and distinct provincial lineages.
Conclusions:
- The recombinant virus likely originated from a mixed infection in northern China in early 1991.
- Rapid spread occurred through multiple transmission chains, reaching populous areas within a year.
- The findings highlight the potential for rapid evolution and dissemination of poliovirus recombinants.