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Mouse adaptation of a sub-genogroup B5 strain of human enterovirus 71 is associated with a novel lysine to glutamic acid substitution at position 244 in protein VP1.
- Source :
-
Virus research [Virus Res] 2012 Jul; Vol. 167 (1), pp. 86-96. Date of Electronic Publication: 2012 Apr 30. - Publication Year :
- 2012
-
Abstract
- Most human enterovirus 71 (HEV71) strains infect only primates and are unable to cause clinically apparent infection in mice. Here we describe a mouse-adapted HEV71 strain that belongs to sub-genogroup B5 with increased virulence in newborn BALB/c mice. The mouse-virulent strain was initially selected by serial passage of a HEV71 clinical isolate (HEV71-B5) in Chinese hamster ovary (CHO) cells (CHO-B5), followed by serial passage in newborn mice. Virus from the fifth mouse passage was cultured twice on Vero cells and designated as MP-B5. MP-B5 induces severe disease of high mortality in newborn mice in a dose-dependent manner. Skeletal muscle is the primary site of virus replication and results in severe myositis. CHO-B5 harbours a single amino acid substitution (K(149) → I) in the VP2 capsid protein. Five additional nucleotide sequence changes were identified in MP-B5, two of which are located in the 5' UTR and the three within the open reading frame (ORF). Two of the ORF mutations resulted in deduced amino acid changes in the capsid protein VP1: S(241) → L and K(244) → E; the third ORF mutation was a synonymous C → T change at nucleotide position 6072 within the 3D polymerase gene. Infectious cDNA clone-derived mutant virus populations of HEV71 belonging to sub-genogroup B3 (CHO-26 M) that contain the VP1 mutations identified in MP-B5 were generated in order to determine the mutation(s) responsible for mouse virulence. Only viruses expressing the VP1 (K(244) → E) mutation were virulent in 5-day-old BALB/c mice, indicating that the VP1 (K(244) → E) change is the critical genetic determinant of mouse adaptation and virulence in this model.<br /> (Copyright © 2012 Elsevier B.V. All rights reserved.)
- Subjects :
- 5' Untranslated Regions
Adaptation, Physiological
Amino Acid Motifs
Amino Acid Sequence
Animals
CHO Cells
Capsid Proteins metabolism
Cell Line
Cricetinae
Enterovirus A, Human classification
Enterovirus A, Human pathogenicity
Enterovirus A, Human physiology
Enterovirus Infections physiopathology
Glutamic Acid metabolism
Humans
Lysine metabolism
Mice
Mice, Inbred BALB C
Molecular Sequence Data
Mutation, Missense
Open Reading Frames
Virulence
Amino Acid Substitution
Capsid Proteins chemistry
Capsid Proteins genetics
Enterovirus A, Human genetics
Enterovirus Infections virology
Glutamic Acid genetics
Lysine genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1872-7492
- Volume :
- 167
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Virus research
- Publication Type :
- Academic Journal
- Accession number :
- 22575826
- Full Text :
- https://doi.org/10.1016/j.virusres.2012.04.009