Novel phylogenetic algorithm to monitor human tropism in Egyptian H5N1-HPAIV reveals evolution toward efficient human-to-human transmission

PLoS One. 2013 Apr 26;8(4):e61572. doi: 10.1371/journal.pone.0061572. Print 2013.

Abstract

Years of endemic infections with highly pathogenic avian influenza (HPAI) A subtype H5N1 virus in poultry and high numbers of infections in humans provide ample opportunity in Egypt for H5N1-HPAIV to develop pandemic potential. In an effort to better understand the viral determinants that facilitate human infections of the Egyptian H5N1-HPAIVvirus, we developed a new phylogenetic algorithm based on a new distance measure derived from the informational spectrum method (ISM). This new approach, which describes functional aspects of the evolution of the hemagglutinin subunit 1 (HA1), revealed a growing group G2 of H5N1-HPAIV in Egypt after 2009 that acquired new informational spectrum (IS) properties suggestive of an increased human tropism and pandemic potential. While in 2006 all viruses in Egypt belonged to the G1 group, by 2011 these viruses were virtually replaced by G2 viruses. All of the G2 viruses displayed four characteristic mutations (D43N, S120(D,N), (S,L)129Δ and I151T), three of which were previously reported to increase binding to the human receptor. Already in 2006-2008 G2 viruses were significantly (p<0.02) more often found in humans than expected from their overall prevalence and this further increased in 2009-2011 (p<0.007). Our approach also identified viruses that acquired additional mutations that we predict to further enhance their human tropism. The extensive evolution of Egyptian H5N1-HPAIV towards a preferential human tropism underlines an urgent need to closely monitor these viruses with respect to molecular determinants of virulence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms*
  • Animals
  • Chickens
  • Egypt / epidemiology
  • Epidemiological Monitoring
  • Evolution, Molecular
  • Hemagglutinin Glycoproteins, Influenza Virus / classification
  • Hemagglutinin Glycoproteins, Influenza Virus / genetics*
  • Humans
  • Influenza A Virus, H5N1 Subtype / classification
  • Influenza A Virus, H5N1 Subtype / genetics*
  • Influenza A Virus, H5N1 Subtype / pathogenicity*
  • Influenza in Birds / epidemiology
  • Influenza in Birds / transmission
  • Influenza in Birds / virology
  • Influenza, Human / epidemiology
  • Influenza, Human / transmission*
  • Influenza, Human / virology
  • Mutation
  • Pandemics / prevention & control*
  • Phylogeny*
  • Receptors, Virus / metabolism
  • Viral Tropism / genetics*
  • Virulence

Substances

  • Hemagglutinin Glycoproteins, Influenza Virus
  • Receptors, Virus

Grant support

This work was supported by the Ministry of Science and Technological Development of the Republic of Serbia (Grant no. 173001, www.mpn.gov.rs) and the Ministry of Foreign Affairs, Luxembourg. They had no role in study design, data collection and analysis, decision to publish, preparation of the manuscript.