Distinguish vaccine strain and wild type strain of yellow fever virus imported to China using high-throughput sequencing technology

Abstract

Objective To identify whether the three imported yellow fever cases in China in March 2016 were infections by wild type strain of yellow fever virus in Angola in 2016, vaccine-associated disease or co-infection of both. Methods Sequences of three yellow fever virus strains were obtained by high-throughput sequencing with IonTorrent PGM platform from blood or urine samples of three yellow fever cases, and their genomic characteristics were analyzed. Then the regions with relatively great difference between the wild type strain and 17D vaccine strain were identified, and then served as the reference sequences when mapping the reads obtained by high-throughput sequencing. Results Partial yellow fever virus genomes were obtained from three samples of yellow fever patients, among them a full length coding region sequence was gained in sample 2. Comparing the genome sequences, the three newly obtained strains of yellow fever virus were highly similar to strain CNYF01R / 2016 which was isolated from the first imported yellow fever case to China in 2016 and strain Angola 71 from Angola in 1971, and they all belonged to Angola genotype of yellow fever virus. In this study, we found five regions in yellow fever virus genomes with great diversity between the vaccine strain and the wild type strain. In these five regions, a number of short reads obtained by high-throughput sequencing of the three samples were mapped to the sequence of wild type virus, while no short reads matched the vaccine strain. Conclusions There were no viral nucleic acid of 17D vaccine strain in the blood or urine samples of these three cases of yellow fever. They are all infected by wild type strains of Angola in 2016. Key words: Yellow fever virus; High-throughput sequencing