Abstract
An outbreak of echovirus 5 (ECV 5) occurred in Korea in 2006, marking the first time this virus had been identified in the country since enterovirus surveillance began in 1993. Using a sample isolated from a young male patient with aseptic meningitis, we performed sequencing of the Korean ECV 5 strain and compared it with a prototype strain (Noyce). At the nucleotide level, the P1 region (85.3%) had the highest identity value; at the amino acid level, the P3 region (98.0%) had the highest identity value. The two strains shared all cleavage sites, with the exception of the VP1/2A site, which was TY/GA in the Noyce strain but TR/GA in the Korean ECV 5 isolate. In Vero cells infected with the Korean ECV 5 isolate, no cytotoxicity was observed in the presence of azidothymidine, acyclovir, amantadine, lamivudine, or ribavirin, when the drugs were administered at a CC50 value >100 μg/mL. Of the five drugs, only amantadine (IC50: 1 ± 0.42 μg/mL, TI: 100) and ribavirin (IC50: 22 ± 1.36 μg/mL, TI: 4.55) had any antiviral activity against the Korean ECV 5 isolate.
1. Introduction
Human enteroviruses (HEV) are RNA viruses from the Picornaviridae family. The 80 immunologically-distinct serotypes that are known to cause infections in humans can be grouped as follows: polioviruses (PV), echoviruses (ECV), coxsackieviruses A (CVA), coxsackieviruses B (CVB), and enterovirus (EV) types 68-71. These viruses are also classified genetically into five species (HEV-A to HEV-D and PVs). HEV-B group containing ECV 5 are CBV 1 to 6, CVA9, ECV 1 to ECV 7, ECV 9, ECV 11 to ECV 21, ECV 24 to ECV 27, ECV 29 to 33, EV 69, EV 73.
ECV cause the same types of infections in humans as the CVB group, but are given a distinct classification primarily because they lack pathogenicity in newborn mice. There are, however, strains of ECV that are pathogenic in mice. ECV 5 infections have been associated with a wide variety of neurological and exanthematic diseases. The prototype strain of ECV 5 was isolated from a patient with aseptic meningitis and was later grouped as the fifth enterovirus serotype. An outbreak of aseptic meningitis caused by ECV 5 occurred in Korea in 2006, marking the first time that ECV 5 had been identified in the country since enterovirus surveillance began in 1993.
The ECV 5 genome contains approximately 7,500 nucleotide-long single-stranded RNA molecules with polarity and carries a small viral peptide (VPg) covalently attached to its 5′ end. The 5′ untranslated region (UTR) of the RNA is approximately 700 nt in length and is unusually long compared with the homologous region of cellular mRNA. The internal ribosomal entry site (IRES) was discovered in the 5′ UTR of the HEVs. In these viruses, the IRES can fold to be a functional secondary RNA structure and drive translation initiation [10]. The coding region encompasses a single open reading frame that encodes a polyprotein divided into three sub-regions, P1, P2, and P3. The P1 region encodes the genetic information of four structural proteins, VP4, VP2, VP3, and VP1. The non-structural proteins are encoded in the P2 (2A-2C) and P3 (3A-3D) regions. A short 3′ UTR of approximately 100 nt separates the coding region from the poly (A) tail.