부산대학교 도서관

Worldwide outbreaks of enterovirus D68 (EV-D68) in 2014 and 2016 have caused serious respiratory and neurological disease. We collected samples from several European countries during the 2018 outbreak and determined 53 near full-length genome ('whole genome') sequences. These sequences were combined with 718 whole genome and 1,987 VP1-gene publicly available sequences. In 2018, circulating strains clustered into multiple subgroups in the B3 and A2 subclades, with different phylogenetic origins. Clusters in subclade B3 emerged from strains circulating primarily in the US and Europe in 2016, though some had deeper roots linking to Asian strains, while clusters in A2 traced back to strains detected in East Asia in 2015-2016. In 2018, all sequences from the USA formed a distinct subgroup, containing only three non-US samples. Alongside the varied origins of seasonal strains, we found that diversification of these variants begins up to 18 months prior to the first diagnostic detection during a EV-D68 season. EV-D68 displays strong signs of continuous antigenic evolution and all 2018 A2 strains had novel patterns in the putative neutralizing epitopes in the BC- and DE-loops. The pattern in the BC-loop of the USA B3 subgroup had not been detected on that continent before. Patients with EV-D68 in subclade A2 were significantly older than patients with a B3 subclade virus. In contrast to other subclades, the age distribution of A2 is distinctly bimodal and was found primarily among children and in the elderly. We hypothesize that EV-D68's rapid evolution of surface proteins, extensive diversity, and high rate of geographic mixing could be explained by substantial reinfection of adults. Better understanding of evolution and immunity across diverse viral pathogens, including EV-D68 and SARS-CoV-2, is critical to pandemic preparedness in the future. Author summary: Enterovirus D68 (EV-D68) has caused punctuated, global outbreaks of respiratory illness and neurological disease, including being implicated as the cause of acute flaccid myelitis (AFM). Serology studies and surveillance data suggests almost everyone is infected during early childhood. The majority of sequences collected are from young children, while adults retain high antibody titers against strains that circulated when they were young. However, little is known about how outbreaks are connected and how the virus evolves and spreads around the globe. Despite EV-D68's apparent reliance on young, naive hosts, EV-D68 antibody binding sites are reportedly evolving under antigenic pressure, and EV-D68 seems to spread rapidly during outbreaks. In this multi-center European collaboration, we confirm that subclade specific age differences are present in those infected. Further, we were able to quantify between- and within-country migration and the 'hidden' diversification that indicates unsampled circulation between outbreaks. We conclude that the evolution of EV-D68 may be driven by substantial re-infection of adults, explaining the rapid geographic mixing and continuous antigenic evolution. The presence of largely unsampled circulation prior to outbreaks suggests there are gaps in current surveillance practices which could be addressed by expanding genetic surveillance. [ABSTRACT FROM AUTHOR]