title: Novel phylogenetic algorithm to monitor human tropism in Egyptian H5N1-HPAIV reveals evolution toward efficient human-to-human transmission.
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.
authors: Center for Multidisciplinary Research, Institute of Nuclear Sciences Vinca, University of Belgrade, Belgrade, Serbia.
authors: Vladimir R
authors: VR
authors: Perovic
authors: Claude P
authors: CP
authors: Muller
authors: Henry L
authors: HL
authors: Niman
authors: Nevena
authors: N
authors: Veljkovic
authors: Ursula
authors: U
authors: Dietrich
authors: Dusan D
authors: DD
authors: Tosic
authors: Sanja
authors: S
authors: Glisic
authors: Veljko
authors: V
authors: Veljkovic
mesh_terms: D000465:Algorithms; D000818:Animals; D002645:Chickens; D004534:Egypt / Q000453:epidemiology; D062665:Epidemiological Monitoring; D019143:Evolution, Molecular; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000145:classification / Q000235:genetics*; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000145:classification / Q000235:genetics* / Q000472:pathogenicity*; D005585:Influenza in Birds / Q000453:epidemiology / Q000635:transmission / Q000821:virology; D007251:Influenza, Human / Q000453:epidemiology / Q000635:transmission* / Q000821:virology; D009154:Mutation; D058873:Pandemics / Q000517:prevention & control*; D010802:Phylogeny; D011991:Receptors, Virus / Q000378:metabolism; D056189:Viral Tropism / Q000235:genetics*; D014774:Virulence
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D011991:Receptors, Virus
references: Virology. 2012 Jan 5;422(1):105-13
references: 22056389
references: PLoS One. 2009 Nov 20;4(11):e7918
references: 19936250
references: BMC Struct Biol. 2009 Sep 28;9:62
references: 19785758
references: Biometrics. 1999 Mar;55(1):1-12
references: 11318142
references: Arch Virol. 2011 Oct;156(10):1803-12
references: 21744000
references: PLoS One. 2011 Mar 21;6(3):e17730
references: 21445292
references: Science. 1967 Jan 20;155(3760):279-84
references: 5334057
references: IEEE Trans Biomed Eng. 1985 May;32(5):337-41
references: 2581884
references: J Mol Evol. 1980 Dec;16(2):111-20
references: 7463489
references: Virol J. 2011 Jun 08;8:283
references: 21651796
references: PLoS Pathog. 2011 May;7(5):e1002068
references: 21637809
references: Avian Dis. 2008 Jun;52(2):269-77
references: 18646456
references: J Gen Virol. 2008 Aug;89(Pt 8):1805-1810
references: 18632950
references: Curr Opin Virol. 2012 Apr;2(2):160-7
references: 22445963
references: J Virol. 2009 Oct;83(19):9901-10
references: 19625397
references: Mol Biol Evol. 1987 Jul;4(4):406-25
references: 3447015
references: PLoS One. 2012;7(5):e38126
references: 22662275
references: J Virol Methods. 2009 Aug;159(2):244-50
references: 19406157
references: Virology. 2011 Apr 25;413(1):139-47
references: 21397290
references: J Virol. 2012 Mar;86(6):2978-89
references: 22238297
references: Arch Virol. 2008;153(12):2253-61
references: 19020946
references: Curr Protein Pept Sci. 2008 Oct;9(5):493-506
references: 18855700
references: Avian Dis. 2010 Mar;54(1 Suppl):345-9
references: 20521657
references: PLoS One. 2009;4(3):e4842
references: 19290041
references: BMC Struct Biol. 2009 Apr 07;9:21
references: 19351406
references: Emerg Infect Dis. 2007 Jul;13(7):1120-1
references: 18214200
references: J Virol. 2010 Jul;84(13):6825-33
references: 20392847
references: J Infect Dis. 2012 Jan 1;205(1):4-6
references: 22080097
references: Curr Med Chem. 2007;14(4):441-53
references: 17305545
references: Methods Enzymol. 1996;266:368-82
references: 8743694
references: Nature. 2006 Nov 16;444(7117):378-82
references: 17108965