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PMID: 12163611 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Molecular analysis of three Ljungan virus isolates reveals a new, close-to-root lineage of the Picornaviridae with a cluster of two unrelated 2A proteins.

Journal of virology ·Vol. 76 ·No. 17 ·2002-09-00 ·Pages 8920-30

Johansson S, Niklasson B, Maizel J, Gorbalenya AE, Lindberg AM

Abstract

Ljungan virus (LV) is a suspected human pathogen recently isolated from bank voles (Clethrionomys glareolus). In the present study, it is revealed through comparative sequence analysis that three newly determined Swedish LV genomes are closely related and possess a deviant picornavirus-like organization: 5' untranslated region-VP0-VP3-VP1-2A1-2A2-2B-2C-3A-3B-3C-3D-3' untranslated region. The LV genomes and the polyproteins encoded by them exhibit several exceptional features, such as the absence of a predicted maturation cleavage of VP0, a conserved sequence determinant in VP0 that is typically found in VP1 of other picornaviruses, and a cluster of two unrelated 2A proteins. The 2A1 protein is related to the 2A protein of cardio-, erbo-, tescho-, and aphthoviruses, and the 2A2 protein is related to the 2A protein of parechoviruses, kobuviruses, and avian encephalomyelitis virus. The unprecedented association of two structurally different 2A proteins is a feature never previously observed among picornaviruses and implies that their functions are not mutually exclusive. Secondary polyprotein processing of the LV polyprotein is mediated by proteinase 3C (3C(pro)) possessing canonical affinity to Glu and Gln at the P1 position and small amino acid residues at the P1' position. In addition, LV 3C(pro) appears to have unique substrate specificity to Asn, Gln, and Asp and to bulky hydrophobic residues at the P2 and P4 positions, respectively. Phylogenetic analysis suggests that LVs form a separate division, which, together with the Parechovirus genus, has branched off the picornavirus tree most closely to its root. The presence of two 2A proteins indicates that some contemporary picornaviruses with a single 2A may have evolved from the ancestral multi-2A picornavirus.

MeSH Terms
3' Untranslated Regions/chemistry,genetics 5' Untranslated Regions/chemistry,genetics Amino Acid Sequence Animals Base Sequence Computational Biology/methods Genome, Viral Humans Molecular Sequence Data Nucleic Acid Conformation Phylogeny Picornaviridae/classification,genetics Polyproteins/metabolism Sequence Alignment Sequence Analysis, DNA Viral Nonstructural Proteins/genetics,metabolism
Chemicals
3' Untranslated Regions 5' Untranslated Regions Polyproteins Viral Nonstructural Proteins
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Johansson Susanne
Department of Chemistry and Biomedical Sciences, University of Kalmar, S-391 82 Kalmar, Sweden.
Niklasson Bo
Maizel Jacob
Gorbalenya Alexander E
Lindberg A Michael
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/jvi.76.17.8920-8930.2002
Published
2002-09-00
Pages
8920-30
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC137002
Subset
IM
Grants
NCI NIH HHS · N01CO12400 · United States
NCI NIH HHS · N01-CO-12400 · United States
NCI NIH HHS · N01-CO-56000 · United States
Databases
GENBANK
AF327920, AF327921, AF327922
External Links
PubMed source DOI: 10.1128/jvi.76.17.8920-8930.2002 PMC Full Text View journal details
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