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Evidence for differing evolutionary dynamics of A/H5N1 viruses among countries applying or not applying avian influenza vaccination in poultry

Giovanni Cattolia, Corresponding Author Contact Information, E-mail The Corresponding Author, Alice Fusaroa, Isabella Monnea, Fethyie Covenb, Tony Joannisc, Hatem S. Abd El-Hamidd, Aly Ahmed Husseine, Claire Corneliusf, Nadim Mukhles Amaring, Marzia Mancina, Edward C. Holmesh, i, Ilaria Capuaa

a Istituto Zooprofilattico Sperimentale delle Venezie, Research & Development Department, OIE/FAO and National Reference Laboratory for Newcastle Disease and Avian Influenza, OIE Collaborating Centre for Diseases at the Human–Animal Interface, Viale dell’Università 10, 35020, Legnaro, Padova, Italy
b Bornova Veterinary Control and Research Institute, İzmir, Turkey
c National Veterinary Research Institute, P.M.B. 01 VOM, Plateau State, Nigeria
d Faculty Veterinary Medicine Damanhour University, Egypt
e Faculty Veterinary Medicine, Cairo University, Giza, Egypt
f US Naval Medical Research Unit No. 3, Cairo, Egypt
g Boehringer Ingelheim, Regional Technical Manager, Dubai, United Arab Emirates
h Center for Infectious Disease Dynamics, Department of Biology, The Pennsylvania State University, Mueller Laboratory, University Park, PA 16802, USA
i Fogarty International Center, National Institutes of Health, Bethesda, MD 20892, USA

Received 27 April 2011; revised 26 September 2011; Accepted 30 September 2011. Available online 12 October 2011.

Highly pathogenic avian influenza (HPAI) H5N1 (clade 2.2) was introduced into Egypt in early 2006. Despite the control measures taken, including mass vaccination of poultry, the virus rapidly spread among commercial and backyard flocks. Since the initial outbreaks, the virus in Egypt has evolved into a third order clade (clade 2.2.1) and diverged into antigenically and genetically distinct subclades. To better understand the dynamics of HPAI H5N1 evolution in countries that differ in vaccination policy, we undertook an in-depth analysis of those virus strains circulating in Egypt between 2006 and 2010, and compared countries where vaccination was adopted (Egypt and Indonesia) to those where it was not (Nigeria, Turkey and Thailand). This study incorporated 751 sequences (Egypt n = 309, Indonesia n = 149, Nigeria n = 106, Turkey n = 87, Thailand n = 100) of the complete haemagglutinin (HA) open reading frame, the major antigenic determinant of influenza A virus. Our analysis revealed that two main Egyptian subclades (termed A and B) have co-circulated in domestic poultry since late 2007 and exhibit different profiles of positively selected codons and rates of nucleotide substitution. The mean evolutionary rate of subclade A H5N1 viruses was 4.07 × 10−3 nucleotide substitutions per site, per year (HPD 95%, 3.23–4.91), whereas subclade B possessed a markedly higher substitution rate (8.87 × 10−3; 95% HPD 7.0–10.72 × 10−3) and a stronger signature of positive selection. Although the direct association between H5N1 vaccination and virus evolution is difficult to establish, we found evidence for a difference in the evolutionary dynamics of H5N1 viruses among countries where vaccination was or was not adopted. In particular, both evolutionary rates and the number of positively selected sites were higher in virus populations circulating in countries applying avian influenza vaccination for H5N1, compared to viruses circulating in countries which had never used vaccination. We therefore urge a greater consideration of the potential consequences of inadequate vaccination on viral evolution.

► Phylogenetic and evolutionary analysis of Egyptian H5N1 viruses was undertaken. ► Evolution of H5N1 in countries applying or not vaccination was compared. ► Distinct Egyptian H5N1 subclades have co-circulated in poultry since late 2007. ► Evolutionary rates were different among countries applying or not vaccination.