Enterovirus 94, a proposed new serotype in human enterovirus species D

Abstract

The genus Enterovirus (family Picornaviridae) contains five species with strains isolated from humans: Human enterovirus A (HEV-A), HEV-B, HEV-C, HEV-D and Poliovirus. In this study, a proposed new serotype of HEV-D was characterized. Four virus strains were isolated from sewage in Egypt and one strain from acute flaccid paralysis cases in the Democratic Republic of the Congo. The complete genome of one environmental isolate, the complete coding sequence of one clinical isolate and complete VP1 regions from the other isolates were sequenced. These isolates had 66.6-69.4 % nucleotide similarity and 74.7-76.6 % amino acid sequence similarity in the VP1 region with the closest enterovirus serotype, enterovirus 70 (EV70), suggesting that the isolates form a new enterovirus type, tentatively designated enterovirus 94 (EV94). Phylogenetic analyses including sequences of the 59 UTR, VP1 and 3D regions demonstrated that EV94 isolates formed a monophyletic group within the species HEV-D. No evidence of recombination was found between EV94 and the other HEV-D serotypes, EV68 and EV70. Further biological characterization showed that EV94 was acid stable and had a wide cell tropism in vitro. Attempts to prevent replication with protective antibodies to known enterovirus receptors (poliovirus receptor, vitronectin a v b 3 receptor and decay accelerating factor) were not successful. Seroprevalence studies in the Finnish population revealed a high prevalence of this virus over the past two decades. INTRODUCTIONThe genus Enterovirus (family Picornaviridae) contains a large group of human pathogens. Although the majority of enterovirus infections are subclinical, enterovirus infection can lead to a variety of acute and chronic diseases including mild upper respiratory illness, febrile rash, aseptic meningitis, encephalitis, acute haemorrhagic conjunctivitis, pleurodynia, acute flaccid paralysis (AFP), diabetes, myocarditis and neonatal sepsis-like disease (Pallansch & Roos, 2001). The primary site of enterovirus infection is the mucosal tissue of the respiratory or gastrointestinal tract. After spreading through the lymphatic system and circulation, the virus can infect secondary target tissues. The secondary replication sites largely define the clinical manifestations of a given enterovirus strain. In the intestinal mucosa, virus replication can continue for several weeks, during which time progeny virus is shed into faeces.The enterovirus genome is a single-stranded RNA molecule of approximately 7500 nt consisting of a single open reading frame flanked by non-coding 59 and 39 regions. The 59 UTR contains an internal ribosome-binding site, which is essential for translation initiation (Pelletier & Sonenberg, 1988;Molla et al., 1992;Chen & Sarnow, 1995). The 39 UTR forms highly conserved secondary and tertiary structures that are thought to be important in replication initiation (Pilipenko et al., 1992(Pilipenko et al., , 1996Mirmomeni et al., 1997). The open reading frame is translated into a single, large polypeptide, which is...

Antigenic and Receptor Binding Properties of Enterovirus 68

“…In the species human enterovirus D (HEV-D), three serotypes, including EV68, EV70, and EV94 are known to causes illness in human (31,32). The VP1 sequences, the most variable genome region of enteroviruses, EV68 were shown to be closely related to those of EV70 and EV94 (26,32).…”

“…The VP1 sequences, the most variable genome region of enteroviruses, EV68 were shown to be closely related to those of EV70 and EV94 (26,32). It was previously reported that EV70 has affinity for ␣2-3 SAs (33).…”

Detection and Genetic Characterization of Enteroviruses Circulating among Wild Populations of Chimpanzees in Cameroon: Relationship with Human and Simian Enteroviruses

“…EV70 was indeed first discovered in Ghana in 1969 during an acute hemorrhagic conjunctivitis epidemic (15) and has subsequently caused two global human pandemics with over 30 million cases reported worldwide (14), consistent with a sub-Saharan origin for this virus. A putative African origin for EV94 in species D was suggested by its initial detection in acute flaccid paralysis patients in the DRC and its recovery from wastewater in Egypt as part of a poliovirus surveillance program (12,34). Furthermore, neutralizing antibodies against EV70 have been detected in the sera of African cattle, sheep, swine, chickens, goats, and dogs (16), implying a much wider host range than typically found in other enterovirus species and consistent with in vitro observations of its ability, along with EV94 to replicate in the cells derived from a wide range of mammalian species (33,34,37).…”

“…A putative African origin for EV94 in species D was suggested by its initial detection in acute flaccid paralysis patients in the DRC and its recovery from wastewater in Egypt as part of a poliovirus surveillance program (12,34). Furthermore, neutralizing antibodies against EV70 have been detected in the sera of African cattle, sheep, swine, chickens, goats, and dogs (16), implying a much wider host range than typically found in other enterovirus species and consistent with in vitro observations of its ability, along with EV94 to replicate in the cells derived from a wide range of mammalian species (33,34,37). The finding of a further species D enterovirus in chimpanzees is thus entirely consistent with widespread circulation in a range of mammalian species in sub-Saharan Africa.…”

Molecular Analysis of Enteroviruses

“…Recombination within the 5' UTR and the non-structural coding regions was also found among EV-A and EV-B members (within the same species) [129;134]. The frequency of recombination differs between EV species, being higher in EV-B species than in EV-A species [8] and very low in EV-D species [135,136].…”