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Limited inter- and intra-patient sequence diversity of the genetic lineage A human metapneumovirus fusion gene

Winther, Thilde Nordmann; Madsen, Chris D LU ; Pedersen, Anders G; von Linstow, Marie-Louise; Eugen-Olsen, Jesper and Hogh, Birthe (2005) In Virus Genes 31(1). p.89-97
Abstract

Human metapneumovirus (hMPV) is associated with respiratory tract illness especially in young children. Two hMPV genetic lineages, A and B, and four sublineages A1, A2 and B1, B2 have been defined. Infection with hMPV occurs through membrane fusion mediated by the hMPV fusion (F) protein. In this study, the inter- and intra-patient genetic diversity of the lineage A hMPV F gene was investigated. Ten isolates were collected from 10 hMPV infected children. Viral RNA was isolated and amplified, and approximately 10 clones from each isolate were sequenced. Altogether 108 clones were successfully sequenced. The average interpatient sequence diversity was 1.68% and 1.64% at nucleotide and amino acid levels, respectively. The samples were... (More)

Human metapneumovirus (hMPV) is associated with respiratory tract illness especially in young children. Two hMPV genetic lineages, A and B, and four sublineages A1, A2 and B1, B2 have been defined. Infection with hMPV occurs through membrane fusion mediated by the hMPV fusion (F) protein. In this study, the inter- and intra-patient genetic diversity of the lineage A hMPV F gene was investigated. Ten isolates were collected from 10 hMPV infected children. Viral RNA was isolated and amplified, and approximately 10 clones from each isolate were sequenced. Altogether 108 clones were successfully sequenced. The average interpatient sequence diversity was 1.68% and 1.64% at nucleotide and amino acid levels, respectively. The samples were divisible into two groups on the basis of intrapatient sequence diversity. In group 1 (4 children) the intra-patient sequence diversity was low (nt: 0.26-0.39%, aa: 0.51-0.94%) whereas group 2 (6 children) had a higher intra-patient sequence diversity (nt: 0.85-1.98%, aa: 1.08-2.22%). Phylogenetic analyses showed that the group 1 children harboured sublineage Al only, but interestingly group 2 children harboured both sublineages Al and A2, indicating they had been infected with at least two viruses. Several independent viruses contained premature stop codons in exactly identical positions resulting in truncated fusion proteins. Possibly this is a mechanism for immune system evasion. The F protein is a major antigenic determinant, and the limited sequence diversity observed lay emphasis on the hMPV F gene as a putative target for future vaccine development.

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published
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keywords
Amino Acid Sequence, Base Sequence, Child, Child, Preschool, Female, Genetic Variation, Humans, Infant, Male, Metapneumovirus, Molecular Sequence Data, Paramyxoviridae Infections, Phylogeny, Sequence Alignment, Viral Fusion Proteins, Journal Article, Research Support, Non-U.S. Gov't
in
Virus Genes
volume
31
issue
1
pages
89 - 97
publisher
Springer Netherlands
external identifiers
  • scopus:21244443121
ISSN
0920-8569
DOI
10.1007/s11262-005-2204-0
language
English
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no
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058576df-372e-4e17-a294-c7ab948b33f6
date added to LUP
2016-12-06 10:19:40
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2017-06-19 12:35:48
@article{058576df-372e-4e17-a294-c7ab948b33f6,
  abstract     = {<p>Human metapneumovirus (hMPV) is associated with respiratory tract illness especially in young children. Two hMPV genetic lineages, A and B, and four sublineages A1, A2 and B1, B2 have been defined. Infection with hMPV occurs through membrane fusion mediated by the hMPV fusion (F) protein. In this study, the inter- and intra-patient genetic diversity of the lineage A hMPV F gene was investigated. Ten isolates were collected from 10 hMPV infected children. Viral RNA was isolated and amplified, and approximately 10 clones from each isolate were sequenced. Altogether 108 clones were successfully sequenced. The average interpatient sequence diversity was 1.68% and 1.64% at nucleotide and amino acid levels, respectively. The samples were divisible into two groups on the basis of intrapatient sequence diversity. In group 1 (4 children) the intra-patient sequence diversity was low (nt: 0.26-0.39%, aa: 0.51-0.94%) whereas group 2 (6 children) had a higher intra-patient sequence diversity (nt: 0.85-1.98%, aa: 1.08-2.22%). Phylogenetic analyses showed that the group 1 children harboured sublineage Al only, but interestingly group 2 children harboured both sublineages Al and A2, indicating they had been infected with at least two viruses. Several independent viruses contained premature stop codons in exactly identical positions resulting in truncated fusion proteins. Possibly this is a mechanism for immune system evasion. The F protein is a major antigenic determinant, and the limited sequence diversity observed lay emphasis on the hMPV F gene as a putative target for future vaccine development.</p>},
  author       = {Winther, Thilde Nordmann and Madsen, Chris D and Pedersen, Anders G and von Linstow, Marie-Louise and Eugen-Olsen, Jesper and Hogh, Birthe},
  issn         = {0920-8569},
  keyword      = {Amino Acid Sequence,Base Sequence,Child,Child, Preschool,Female,Genetic Variation,Humans,Infant,Male,Metapneumovirus,Molecular Sequence Data,Paramyxoviridae Infections,Phylogeny,Sequence Alignment,Viral Fusion Proteins,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  number       = {1},
  pages        = {89--97},
  publisher    = {Springer Netherlands},
  series       = {Virus Genes},
  title        = {Limited inter- and intra-patient sequence diversity of the genetic lineage A human metapneumovirus fusion gene},
  url          = {http://dx.doi.org/10.1007/s11262-005-2204-0},
  volume       = {31},
  year         = {2005},
}