title: The matrix gene of influenza A H5N1 in Egypt, 2006-2016: molecular insights and distribution of amantadine-resistant variants.
abstract: Large-scale sequence analysis of Matrix (M) gene and its coding proteins M1 and M2 was performed for 274 highly pathogenic avian influenza viruses H5N1 circulated in Egypt from 2006 to 2016. The aim is to study the amantadine-resistant markers distribution and to estimate the evolutionary rate. 246 viruses were obtained from the Global Initiative on Sharing All Influenza Data base, and 28 additional viruses were sequenced. Maximum clade credibility (MCC) phylogenetic tree revealed that the M gene has evolved into two different lineages. Estimated Evolutionary analysis showed that the M2 protein possessed higher evolutionary rates (3.45 × 10-3) than the M1 protein (2.73 × 10-3). M gene encoding proteins revealed significant markers described to be associated with host tropism and increase in virulence: V15I, N30D, and T121A in M1 and L55F in M2 protein. Site analysis focusing attention on the temporal and host distribution of the amantadine-resistant markers was carried out and showed that vast majority of the M2 amantadine-resistant variants of clade 2.2.1.1 (n = 90) is N31 marker, in addition to G27 (n = 7), A27 (n = 5), I27 (n = 1), and S30 (n = 1). In 2010-2011, amantadine resistant frequency increased considerably resembling more than half of the resistant variants. Notably, all viruses of clade 2.2.1.1 possessed amantadine-resistant marker. However, almost all current circulating viruses in Egypt of clade 2.2.1.2 from 2014 to 2016 did not carry any amantadine-resistant markers.
authors.affiliation: Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, 17493, Greifswald Insel-Riems, Germany. mahmoud.naguib@fli.bund.de.|National Laboratory for Veterinary Quality Control on Poultry Production, Animal Health Research Institute, Giza, 12618, Egypt. mahmoud.naguib@fli.bund.de.
authors.forename: Mahmoud M
authors.identifier: http://orcid.org/0000-0001-6876-8903
authors.initials: MM
authors.lastname: Naguib
authors.affiliation: National Laboratory for Veterinary Quality Control on Poultry Production, Animal Health Research Institute, Giza, 12618, Egypt.
authors.forename: Naglaa
authors.initials: N
authors.lastname: Hagag
authors.affiliation: Department of Virology, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt.
authors.forename: Ahmed A
authors.initials: AA
authors.lastname: El-Sanousi
authors.affiliation: Department of Virology, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt.
authors.forename: Hussein Ali
authors.initials: HA
authors.lastname: Hussein
authors.affiliation: National Laboratory for Veterinary Quality Control on Poultry Production, Animal Health Research Institute, Giza, 12618, Egypt.
authors.forename: Abdel-Satar
authors.initials: AS
authors.lastname: Arafa
mesh_terms: D000547:Amantadine / Q000494:pharmacology*; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002645:Chickens; D024882:Drug Resistance, Viral; D004534:Egypt / Q000453:epidemiology; D005838:Genotype; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000187:drug effects* / Q000235:genetics*; D005585:Influenza in Birds / Q000453:epidemiology / Q000821:virology; D007251:Influenza, Human / Q000453:epidemiology* / Q000266:history / Q000821:virology*; D008958:Models, Molecular; D010802:Phylogeny; D011487:Protein Conformation; D014763:Viral Matrix Proteins / Q000737:chemistry / Q000235:genetics*
chemical_list: D000998:Antiviral Agents; C488936:M1 protein, Influenza A virus; D014763:Viral Matrix Proteins; D000547:Amantadine
keywords: Amantadine resistance; Avian influenza H5N1; M1 protein; M2 protein; Matrix gene