Year: 2012
Type: dissertation
Abstract: Enteroviruses (genus Enterovirus, family Picornaviridae) are small single-stranded RNA viruses associated with a wide variety of acute and chronic dis-eases. The genus Enterovirus consists of ten species. Seven of the species, Human enterovirus A (HEV-A), HEV-B, HEV-C, HEV-D, Human rhinovirus A (HRV-A), HRV-B and HRV-C, cause infections in humans. The enterovirus species are further classified into serotypes (or types) by their antigenic properties and/or, more recently, their sequence similarities. In this thesis, the genetic evidence for the classification of three new enterovi-rus types, enterovirus 94 (EV-94), EV-96 and EV-97, was presented. Further characterisation of prevalence and cell tropism was conducted for one of the new types, EV-94. Sequence analysis methods were used to infer evolutionary relationships between the new and previously known EV types and possible mechanisms behind the emergence of new enterovirus clades. The enterovirus strains characterized in this thesis formed distinct mono-phyletic clades within the species HEV-B, HEV-C and HEV-D on the basis of their capsid-coding regions. These strains had less than 75% nucleotide (< 85% amino acid) sequence similarities with previously known enteroviruses in their VP1 protein coding sequences, suggesting that these strains represent previously unknown enterovirus types, designated as EV-94 (HEV-D), EV-96 (HEV-C) and EV-97 (HEV-B). The complete genome analysis of the EV-96 and EV-97 strains together with the previously characterised HEV-C and HEV-B strains suggested multiple inter-typic recombination events within non-coding and non-structural protein-coding regions of their genomes. No evidence of recombination was de-tected for EV-94 and other members of the HEV-D species. Furthermore, an apparently rare inter-species recombination event between the recently described HEV-A types (EV-90 and EV-91) and a member of the HEV-C/-D species was found at 5 untranslated region (5 UTR) of the genome. EV-94 had unusually wide cell type and host species tropism in vitro and, de-spite recent discovery, a high prevalence of antibodies against EV-94 was detected among the Finnish population during the past three decades. These results indicate that this virus is highly prevalent and capable of invading a wide variety of tissues. The sequence analysis presented in this thesis suggested different evolutionary patterns within enterovirus types (leading to intra-typic lineages) and evolution leading to larger scale (type-specific) differences. Intra-typic genetic change was dominated by silent mutations and amino acid polymorphism at immunogenic sites. Inter-typic comparisons, however, suggested type-specific fixation of amino acids and differences in the location of polymorphic amino acid sites between EV types. These changes were proposed to be accompanied by structural alterations in the capsid proteins, possibly as a result of adaptation to larger scale changes in the environment.
Source: Työväentutkimus Vuosikirja
Author: Teemu Smura
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W592641978