In this study, we analyzed the phylodynamic of N gene of measles virus H1a genotype circulating in Jiangsu province from 2005 to 2017. Our results showed that the change of gene distance of N gene over year is similarly to the change of effective population size of measles virus and incidence of measles cases with year (Figure 1, 2 and 4). H1a genotype measles virus present the pattern of multiple origins in phylogenetic tree, and the virus of multiple origins gradually disappear over time. For example, most of multiple origins of measles virus prevailed in Jiangsu province in 2005 disappeared in 2017. Especially, one of two cluster of H1a genotype circulating in Jiangsu province disappeared in 2016. In recent years, the incidence of measles in Jiangsu province has been maintaining about 1.2 per million population which approaching the elimination goal of measles (the incidence of indigenous measles is less than 1 per million population) (Figure 1). The change pattern of both gene distance of N gene and effective population size are in accordance with the change of the incidence of measles in Jiangsu province. The loss of multiple origins’ measles virus in phylogenetic tree also provide the evidence of measles virus approaching elimination in this region. Moreover, the change in molecular level of N gene of measles virus are prior to that of classic epidemiology surveillance. This implies the priority of molecular epidemiology in measles surveillance and its foreseeability for upcoming epidemic.
Based on the sequence analysis of H and N genes, not only genotype of measles virus was identified[16-18], but also the source of wild types measles viruses associated with outbreaks was inferred[9, 19-21]. For example, the new genotype of measles emerged in a given region was associated with the imported virus by travelers between various countries[22, 23]. Moreover, for a given genotype, the molecular diversity was observed between measles viruses with different geographic origins. Jennifer et al confirmed that resurgence of measles virus in 1994 was more closely related to wild type viruses previously circulating in Europe, Africa, and Japan than the indigenous virus circulating in USA[9]. The indigenous virus was interrupted after the 1989-1922 epidemic in USA. It suggests that to monitor molecular feature of measles virus can provide more helpful information on for classic epidemiology as well as our finding herein.
Measles virus has the ability of higher mutation and replication rates. This variation is modulated by two processes: the host’s immune response to infection and the bottleneck at transmission. The former is elicited by primary infection in pre-vaccine era while by vaccine immunization in vaccine era. The latter includes incubation time, infectious periods, seasonality, population density, and so on. For measles virus, overwhelming immune pressure limits the chance of an adaptive response in vivo. It will lead the appearance of different phylodynamic in various vaccine immunization era. In pre-vaccine era, it shows that many strains coexist in phylogenetics[7]. Nowadays, more than 95% vaccine coverage has reached in many regions. Subsequently, immune pressure become the predominant drivers, and it will make partial epidemic strains die out, and the number of extinct strains will increase with the time of persistent high immune pressure. As described in this study, the cluster 1 disappeared in 2016 and only a small part of strains in cluster 2 survived in 2017.