.2003 To 2007, The Chinese Mainland Rubella Virus Molecular Epidemiological Studies

Rubella is an acute respiratory infectious disease caused by Rubella viruses,and it is a "C" class infectious disease in China.The clinical symptom of Rubella was usually mild and with few complications,but if pregnant women without immunity to rubella attacked by Rubella viruses,it can cause abortion,dead fetus and Congenital Rubella Syndrome(CRS) with multi organs severe injury,this is the most serious compromise.There is only one serotype but several genotypes of Rubella viruses,2 Clades and 13 genotypes were classified with Rubella viruses prevalent in the world by World Health Organization(WHO),and the diversity in nucleotide acids level between these 2 Clades is 8～10%.In this research,viral isolation was performed from throat swab specimens collected from rubella outbreak and sporadic patients in 10 provinces of China during 2003 to 2007 using Vero cell line or Vero/SLAM cell line.57 rubella viral strains were isolated and identified using Indirect lmmunofluoreseent Assay(IFA), Immunochromatography Assay(ICA) and short fragment Reverse Transcription -Polymerase Chain Reaction(RT-PCR) methods.739 fragment of E1 gene (nt8731～nt9469) for molecular epidemiological research were obtained by RT-PCR method.After sequencing and analyisis,the results showed that 55 Chinese rubella virus strains belong to a distinguish branch of 1E genotype,comparing 1E genotype rubella strains from other countries,and other 2 Chinese rubella virus strains belong to 2B genotype.The homology of nucleotide acids among 55 1E genotype Rubella viruses based on 739 nucleotides was 97.8%～100%,and 98.3%～100%was on amino acids level;The homology of nucleotide acids and amino acids between 2 2B genotype Rubella viruses were all 100%;The homology of nucleotide acids between 1E genotype and 2B genotype Rubella viruses was 89.1%～90.1%,and 98.3%～100%was on amino acids level.The within group genetic distance of 55 1E genotype Rubella viruses was 0.014,and the without group genetic distance were 0.013 and 0.026 comparing with 1E genotype Rubella viruses of WHO reference strains(Chinese reference strain T14-CH-02 and M1-MAL-01strain),and was 0.019 comparing with of 1E genotype Rubella viruses of other countries'.From the analysis in terms of vertical time dimension,no obvious changes occurred among Rubella viruses in same period during 2003 to 2007,and it showed that there were several Rubella virus chains continually circulating in China.Most mutations of 57 rubella viruses were silent mutations,and highly conserved among amino acid sequences.Except for only 1 amino acid(Thr²¹²â†'Ser²¹²) of 2 1E rubella viruses at the hemagglutination inhibition and neutralization epitopes,the other important antigenic epitope sites have no changes;there were shared mutation (Leu³³⁸â†'Phe³³⁸) in E1 protein of all Chinese 1E genotype Rubella viruses,while this mutation was not found in 1E genotype Rubella viruses which isolated from other countries.The Phe³³⁸ was the specific mutation consistent with Chinese 1E genotype Rubella viruses.1E genotype Rubella viruses were isolated from all of 10 provinces of China from 2003 to 2007,while 2B genotype Rubella viruses,which seemed imported from Vietnam,were only isolated in Sichuan province in 2006,it showed that 1E genotype was the predominant genotype in this period time,and rubella circulations in recent years were mainly caused by 1E genotype Rubella viruses with multi-transmission routes.1A,2A and 2B genotype Rubella viruses circulated during 1979～1984 and 1F, 2A genotype Rubella viruses circulated during 1999～2002 in China were not isolated in this period,showed that genotype substitutions occurred in this period.Rubella vaccine was arranged into National immunization plan in 2007,and it provides us good opportunities to control rubella in China.At present,integration of Measles and Rubella laboratories network was priority in China,also we should strengthen research of molecular epidemiology of Rubella viruses,to understand the distribution of genotype of Rubella virus in China,to identify the resource and transmission routes,to provide methods for evaluation the effect of rubella control in order to interrupt the transmission of Rubella viruses,these also had important significance to rubella control and elimination in the world.