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

T.N. Winther, C.D. Madsen, Anders Gorm Pedersen, M.L. Von Linstow, J. Eugen-Olsen, B. Hogh

    Research output: Contribution to journalJournal articleResearchpeer-review

    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 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 A1 only, but interestingly group 2 children harboured both sublineages A1 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.
    Original languageEnglish
    JournalVirus Genes
    Volume31
    Issue number1
    Pages (from-to)89-97
    ISSN0920-8569
    Publication statusPublished - 2005

    Keywords

    • hMPV
    • fusion gene
    • phylogenetic analysis
    • sequencing

    Fingerprint Dive into the research topics of 'Limited inter- and intra-patient sequence diversity of the genetic lineage a human metapneumovirus fusion gene'. Together they form a unique fingerprint.

    Cite this