Identification and characteristics of the newly emerged subclades of enterovirus D68 associated with severe respiratory/central nervous system infections in Hong Kong (#117)
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.
- Yip CCY, Lo JYC, Sridhar S, Lung DC, Luk S, Chan KH, Chan JFW, Cheng VCC, Woo PCY, Yuen KY, Lau SKP. First Report of a Fatal Case Associated with EV-D68 Infection in Hong Kong and Emergence of an Interclade Recombinant in China Revealed by Genome Analysis. Int J Mol Sci. 2017 May 16;18(5).
- Lau SK, Yip CC, Zhao PS, Chow WN, To KK, Wu AK, Yuen KY, Woo PC. Enterovirus D68 Infections Associated with Severe Respiratory Illness in Elderly Patients and Emergence of a Novel Clade in Hong Kong. Sci Rep. 2016 Apr 28;6:25147. doi: 10.1038/srep25147.
- Wang G, Zhuge J, Huang W, Nolan SM, Gilrane VL, Yin C, Dimitrova N, Fallon JT. Enterovirus D68 Subclade B3 Strain Circulating and Causing an Outbreak in the United States in 2016. Sci Rep. 2017 Apr 28;7(1):1242. doi: 10.1038/s41598-017-01349-4.
- Dyrdak R, Grabbe M, Hammas B, Ekwall J, Hansson KE, Luthander J, Naucler P, Reinius H, Rotzén-Östlund M, Albert J. Outbreak of enterovirus D68 of the new B3 lineage in Stockholm, Sweden, August to September 2016. Euro Surveill. 2016 Nov 17;21(46). pii: 30403. doi: 10.2807/1560-7917.ES.2016.21.46.30403. Erratum in: Euro Surveill. 2016 Nov 24;21(47):.
- Giombini E, Rueca M, Barberi W, Iori AP, Castilletti C, Scognamiglio P, Vairo F, Ippolito G, Capobianchi MR, Valli MB. Enterovirus D68-Associated Acute Flaccid Myelitis in Immunocompromised Woman, Italy. Emerg Infect Dis. 2017 Oct;23(10):1690-1693. doi: 10.3201/eid2310.170792.