Importation and circulation of rubella virus lineages 1E-L2 and 2B-L2c between 2018 and 2021 in China: Virus evolution and spatial-temporal transmission characteristics

To better understand the importation and circulation patterns of rubella virus lineages 1E-L2 and 2B-L2c circulating in China since 2018, 3,312 viral strains collected from 27 out of 31 provinces in China between 2018 and 2021 were sequenced and analyzed with the representative international strains of lineages 1E-L2 and 2B-L2c based on genotyping region. Time-scale phylogenetic analysis revealed that the global lineages 1E-L2 and 2B-L2c presented distinct evolutionary patterns. Lineage 1E-L2 circulated in relatively limited geographical areas (mainly Asia) and showed geographical and temporal clustering, while lineage 2B-L2c strains circulated widely throughout the world and exhibited a complicated topology with several independently evolved branches. Furthermore, both lineages showed extensive international transmission activities, and phylogeographic inference provided evidence that lineage 1E-L2 strains circulating in China possibly originated from Japan, while the source of lineage 2B-L2c isolated since 2018 is still unclear. After importation into China in 2018, the spread of lineage 1E-L2 presented a three-stage transmission pattern from southern to northern China, whereas lineage 2B-L2c spread from a single point in western China to all the other four regions. These two transmission patterns allowed both imported lineages to spread rapidly across China during the 2018-9 rubella epidemic and eventually established endemic circulations. This study provides critical scientific data for rubella control and elimination in China and worldwide.