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Published on: May 4, 2015
Genetic variability of the G glycoprotein gene of human metapneumovirus
Nathalie Bastien1, Li Liu, Diane Ward
1National Microbiology Laboratory, Canadian Science Center for Human and Animal Health, 1015 Arlington St., Winnipeg, Manitoba, Canada R3E 3R2.
Abstract:
Human metapneumovirus (hMPV) has been associated with respiratory illnesses like those caused by human respiratory syncytial virus (HRSV) infection. Similar to other pneumoviruses, genetic diversity has been reported for hMPV. Little information is currently available on the genetic variability of the G glycoprotein (G), which is the most variable gene in RSV and avian pneumovirus. The complete nucleotide sequences of the G open reading frame (ORF) of 24 Canadian hMPV isolates were determined. Phylogenetic analysis showed the existence of two major groups or clusters (1 and 2). All but one of the hMPV isolates that we examined belonged to cluster 1. Additional genetic variability was observed in cluster 1, which separated into two genetic subclusters. Within cluster 1 the nucleotide sequence identity for the G ORF was 74.2 to 100%, and the identity for the predicted amino acid sequence was 61.4 to 100%. The G genes of cluster 1 isolates were more divergent from the cluster 2 isolates, with 45.6 to 50.5% and 34.2 to 37.2% identity levels for the nucleotide and amino acid sequences, respectively. Sequence analysis also revealed changes in stop codon usage, resulting in G proteins of different lengths (217, 219, 228, and 236 residues). Western blot analysis with the use of hMPV-specific polyclonal antisera to each hMPV cluster showed significant antigenic divergence between the G proteins of clusters 1 and 2. These results suggest that the G protein of hMPV is continuously evolving and that the genetic diversity observed for the hMPV genes is reflected in the antigenic variability, similar to HRSV.
Insights
Human metapneumovirus (hMPV) G protein shows significant genetic and antigenic diversity, evolving continuously. This variability, particularly within cluster 1, impacts viral evolution and immune response, similar to human respiratory syncytial virus (HRSV).
Area of Science:
- Virology
- Molecular Biology
- Immunology
Background:
- Human metapneumovirus (hMPV) causes respiratory illnesses, similar to human respiratory syncytial virus (HRSV).
- Genetic diversity exists in hMPV, but the variability of its G glycoprotein (G) is poorly understood.
- The G protein is known for high variability in related pneumoviruses like RSV and avian pneumovirus.
Purpose of the Study:
- To investigate the genetic variability of the hMPV G glycoprotein (G) gene.
- To analyze the phylogenetic relationships and antigenic properties of different hMPV G protein variants.
- To compare the genetic diversity of hMPV G protein with that of HRSV.
Main Methods:
- Sequencing of the G open reading frame (ORF) from 24 Canadian hMPV isolates.
- Phylogenetic analysis to determine genetic clusters and subclusters.
- Western blot analysis using hMPV-specific polyclonal antisera to assess antigenic divergence.
Main Results:
- Phylogenetic analysis revealed two major hMPV clusters (1 and 2), with most isolates in cluster 1.
- Cluster 1 further divided into two genetic subclusters, showing nucleotide sequence identity from 74.2% to 100% and amino acid identity from 61.4% to 100%.
- Significant nucleotide (45.6–50.5%) and amino acid (34.2–37.2%) divergence was observed between cluster 1 and cluster 2 isolates.
- Stop codon variations resulted in G proteins of varying lengths (217–236 residues).
- Western blot analysis confirmed significant antigenic divergence between cluster 1 and cluster 2 G proteins.
Conclusions:
- The hMPV G protein exhibits continuous evolution and significant genetic diversity.
- Genetic variability in the hMPV G gene correlates with antigenic variability, mirroring patterns seen in HRSV.
- Understanding hMPV G protein diversity is crucial for vaccine development and disease control strategies.
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