Identification And Characteristics Of The Newly Emerged Subclades Of Enterovirus D68 Associated With Severe Respiratory/central Nervous System Infections In Hong Kong

Abstract

Enterovirus D68 (EV-D68) caused a large outbreak in the United States in 2014. But the circulating features of EV-D68 were largely unknown. To better understand the disease impact and evolutionary dynamics of EV-D68, we studied the clinical characteristics of patients and analysed the genetic characteristics of VP1, 2C, 3D genes and the genomes. Total 10,400 nasopharyngeal aspirates (NPAs) from hospitalized patients (2010-2017) were subjected to RT-PCR to detect EV-D68. VP1, 2C and 3D genes of the positive samples were sequenced and subjected to phylogenetic analyses. Recombination Detection Program (RDP4) and Simplot version 3.5.1 were employed to predict potential recombination events. EV-D68 was detected in 56 (0.54%) NPAs from 39 children and 17 adults/elderlies. Phylogenetic analysis identified two strains of EV-D68 clade A, 12 of subclade B1, 19 of subclade B3 (including a 10-year-old boy presented with severe central nervous system syndromes, cardiac arrest and finally death), and 22 of clade D (including all HK strains from adult/elderly patients). Seventeen patients had pneumonia, including 6 elderly patients. A deletion of 12 nucleotides in the 5’ untranslated region and distinct patterns in BC and DE loops were found in strains in clade B. We reported the first fatal case in Hong Kong caused by the newly emerged subclade B3 of EV-D68. All HK strains from adult/elderly patients were belonged to the clade D, indicating an emerging trend in the elderly population. The subclade B3 was the cause of outbreaks in the USA, Sweden, and a fatal case in Italy recently, indicating its potential trend to prevail worldwide. The changes of amino acid residues in the BC and DE loops between different subclades might lead to changes of antigenic episodes, tissue tropism, susceptible populations, and even cause more severe diseases.