A Novel Recombinant Enterovirus Type EV-A89 with Low Epidemic Strength in Xinjiang, China

Abstract

Enterovirus A89 (EV-A89) is a novel member of the EV-A species. To date, only one full-length genome sequence (the prototype strain) has been published. Here, we report the molecular identification and genomic characterization of a Chinese EV-A89 strain, KSYPH-TRMH22F/XJ/CHN/2011, isolated in 2011 from a contact of an acute flaccid paralysis (AFP) patient during AFP case surveillance in Xinjiang China. This was the first report of EV-A89 in China. The VP1 coding sequence of this strain demonstrated 93.2% nucleotide and 99.3% amino acid identity with the EV-A89 prototype strain. In the P2 and P3 regions, the Chinese EV-A89 strain demonstrated markedly higher identity than the prototype strains of EV-A76, EV-A90, and EV-A91, indicating that one or more recombination events between EV-A89 and these EV-A types might have occurred. Long-term evolution of these EV types originated from the same ancestor provides the spatial and temporal circumstances for recombination to occur. An antibody seroprevalence survey against EV-A89 in two Xinjiang prefectures demonstrated low positive rates and low titres of EV-A89 neutralization antibody, suggesting limited range of transmission and exposure to the population. This study provides a solid foundation for further studies on the biological and pathogenic properties of EV-A89.Human enterovirus (EV) infections are usually asymptomatic or bring about only mild disease, such as the common cold or minor undifferentiated febrile illnesses. However, EVs are associated with outbreaks of more serious disease such as acute flaccid paralysis (AFP), acute haemorrhagic conjunctivitis, aseptic meningitis, encephalitis, myocarditis, and hand, foot, and mouth disease (HFMD) [1][2][3][4] , which result in considerable morbidity and occasionally in mortality.EVs belong to the picornaviridae family and fall within the new order Picornavirales, which represents small non-enveloped RNA viruses with a single stranded positive-sense genome of approximately 7500 nucleotides 5 . The EV genome consists of a single open reading frame (ORF) flanked by 5′ and 3′ untranslated regions (UTRs). The ORF is translated into a single, large polyprotein of 2200 amino acids (aa), which is subsequently cleaved by viral proteases into one capsid protein region (P1) and two non-structural regions (P2 and P3). The P1 region encodes four viral capsid proteins: viral protein 1-4 (VP1-VP4), and the P2 and P3 regions encode seven non-structural proteins 2A-2C and 3A-3D, respectively 6 . The 5′ -UTR is about 740 nucleotides long and has an internal ribosome entry site (IRES) that is indispensable for translation initiation 7,8 . The approximately 100 nucleotide 3′ -UTR, located between the ORF and the poly (A) stretch, forms highly conserved secondary and tertiary structures that are involved in RNA replication 9 . Currently, more than 100 human EV serotypes have been described. They are currently classified into four species, EV-A, EV-B, EV-C, and EV-D, according to their genomic characteristics 5,10,11 . The classificatio...

Circulation of multiple serotypes of highly divergent enterovirus C in the Xinjiang Uighur Autonomous Region of China

“…The circulation of EV-C strains should be carefully monitored, because several outbreaks of poliomyelitis caused by cVDPVs containing sequences in the non-structural protein coding region from unidentified sources that are considered to be a result of recombination with EV-C have been documented 21 22 24 . Moreover, many recent studies have shown that such enterovirus species exist as a worldwide reservoir of genetic material, comprising a limited quantity of coding region sets defining a finite number of serotypes and a range of non-structural genes that recombine frequently to produce new virus variants 28 36 40 41 . Recombination between a slightly pathogenic vaccine poliovirus mutant and an EV-C strain may result in a recombinant that is more pathogenic, replicates to higher titers, and is maintained in circulation 23 36 42 .…”

Isolation and Characterization of a Highly Mutated Chinese Isolate of Enterovirus B84 from a Patient with Acute Flaccid Paralysis

“…Molecular serotyping methods based on sequence variation in the VP1 region correlate with the classification based on antigenic properties 21 26 , and have recently replaced the neutralization test as the gold standard for enterovirus serotyping. Since the invention and application of molecular serotyping methods, a considerable number of new EV serotypes have been identified in many Chinese provinces, especially in Shandong 13 27 , Yunnan 14 , Xinjiang 28 29 , Tibet 3 15 30 , and Guangdong 31 . In this study, we report the full-length genome sequence of a recently identified novel serotype, EV-B84, which was also obtained from AFP case surveillance.…”

Phylogenetic characteristics and molecular epidemiological analysis of novel enterovirus EV-B83 isolated from Tibet, China

“…The emergence of molecular typing technology has greatly changed the current situation and accelerated the discovery of novel enteroviruses, which have been increasingly reported 9,[22][23][24] . Currently, there are only two EV-B83 full-length genomic sequences and twelve in the VP1 region with lengths over 600 bp available in GenBank.…”