Charged amino acid variability related to N-glyco -sylation and epitopes in A/H3N2 influenza: Hem -agglutinin and neuraminidase

PLoS One. 2017 Jul 14;12(7):e0178231. doi: 10.1371/journal.pone.0178231. eCollection 2017.

Abstract

Background: The A/H3N2 influenza viruses circulated in humans have been shown to undergo antigenic drift, a process in which amino acid mutations result from nucleotide substitutions. There are few reports regarding the charged amino acid mutations. The purpose of this paper is to explore the relations between charged amino acids, N-glycosylation and epitopes in hemagglutinin (HA) and neuraminidase (NA).

Methods: A total of 700 HA genes (691 NA genes) of A/H3N2 viruses were chronologically analyzed for the mutational variants in amino acid features, N-glycosylation sites and epitopes since its emergence in 1968.

Results: It was found that both the number of HA N-glycosylation sites and the electric charge of HA increased gradually up to 2016. The charges of HA and HA1 increased respectively 1.54-fold (+7.0 /+17.8) and 1.08-fold (+8.0/+16.6) and the number of NGS in nearly doubled (7/12). As great diversities occurred in 1990s, involving Epitope A, B and D mutations, the charged amino acids in Epitopes A, B, C and D in HA1 mutated at a high frequency in global circulating strains last decade. The charged amino acid mutations in Epitopes A (T135K) has shown high mutability in strains near years, resulting in a decrease of NGT135-135. Both K158N and K160T not only involved mutations charged in epitope B, but also caused a gain of NYT158-160. Epitope B and its adjacent N-glycosylation site NYT158-160 mutated more frequently, which might be under greater immune pressure than the rest.

Conclusions: The charged amino acid mutations in A/H3N2 Influenza play a significant role in virus evolution, which might cause an important public health issue. Variability related to both the epitopes (A and B) and N-glycosylation is beneficial for understanding the evolutionary mechanisms, disease pathogenesis and vaccine research.

MeSH terms

  • Amino Acids / metabolism
  • Antigens, Viral / chemistry
  • Antigens, Viral / immunology
  • Antigens, Viral / metabolism
  • Epitopes / chemistry
  • Epitopes / immunology
  • Epitopes / metabolism*
  • Evolution, Molecular
  • Genetic Variation
  • Glycosylation
  • Hemagglutinin Glycoproteins, Influenza Virus / chemistry
  • Hemagglutinin Glycoproteins, Influenza Virus / classification
  • Hemagglutinin Glycoproteins, Influenza Virus / metabolism*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Influenza A Virus, H3N2 Subtype / metabolism*
  • Influenza, Human / pathology
  • Influenza, Human / virology
  • Mutation
  • Neuraminidase / chemistry
  • Neuraminidase / classification
  • Neuraminidase / metabolism*
  • Phylogeny
  • Protein Structure, Tertiary
  • RNA, Viral / chemistry
  • RNA, Viral / isolation & purification
  • RNA, Viral / metabolism
  • Sequence Analysis, RNA

Substances

  • Amino Acids
  • Antigens, Viral
  • Epitopes
  • Hemagglutinin Glycoproteins, Influenza Virus
  • RNA, Viral
  • Neuraminidase

Grants and funding

The Natural Science Foundation of Guangdong Province (2016A030313775), URL:http://www.gdstc.gov.cn/; The Guangzhou Science and Technology Program planning projects (2014J4100084), URL:http://www.gzsi.gov.cn/; The National Natural Science Foundation of China (30972757), URL:http://www.nsfc.gov.cn/; The National Transfer Payments Funding for the 2015 Influenza Survey. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.