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.

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.

Related Concept Videos

Respiratory Syncytial Virus Disease01:29

Respiratory Syncytial Virus Disease

Human respiratory syncytial virus (RSV) is a widespread pathogen that primarily targets infants and young children but also poses a serious health risk to elderly and immunocompromised individuals. Belonging to the Pneumoviridae family, RSV is a negative-sense, single-stranded RNA virus within the Pneumovirus genus. Its global health burden is significant, with millions of cases annually resulting in hospitalizations and mortality, particularly in resource-limited settings. Although most...
Single Nucleotide Polymorphisms-SNPs01:05

Single Nucleotide Polymorphisms-SNPs

A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
Viral Mutations00:36

Viral Mutations

A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material for adaptive...