title: Re-emergence of amantadine-resistant variants among highly pathogenic avian influenza H5N1 viruses in Egypt.
abstract: Highly pathogenic avian influenza (HPAI) H5N1 virus continues to undergo substantial evolution. Emergence of antiviral resistance among H5N1 avian influenza viruses is a major challenge in the control of pandemic influenza. Numerous studies have focused on the genetic and evolutionary dynamics of the hemagglutinin and neuraminidase genes; however, studies on the susceptibility of HPAI H5N1 viruses to amantadine and genetic diversity of the matrix (M) gene are limited. Accordingly, we studied the amantadine susceptibility of the HPAI H5N1 viruses isolated in Egypt during 2006-2015 based on genotypic and phenotypic characteristics. We analyzed data on 253 virus sequences and constructed a phylogenetic tree to calculate selective pressures on sites in the M2 gene associated with amantadine-resistance among different clades. Selection pressure was identified in the transmembrane domain of M2 gene at positions 27 and 31. Amantadine-resistant variants emerged in 2007 but were not circulating between 2012 and 2014. By 2015, amantadine-resistant HPAI H5N1 viruses re-emerged. This may be associated with the uncontrolled prescription of amantadine for prophylaxis and control of avian influenza infections in the poultry farm sector in Egypt. More epidemiological research is required to verify this observation.
authors.affiliation: Center of Scientific Excellence for Influenza Viruses, National Research Centre, Giza, Egypt; Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: Rabeh
authors.initials: R
authors.lastname: El-Shesheny
authors.affiliation: Center of Scientific Excellence for Influenza Viruses, National Research Centre, Giza, Egypt.
authors.forename: Ola
authors.initials: O
authors.lastname: Bagato
authors.affiliation: Center of Scientific Excellence for Influenza Viruses, National Research Centre, Giza, Egypt.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Kandeil
authors.affiliation: Center of Scientific Excellence for Influenza Viruses, National Research Centre, Giza, Egypt.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Mostafa
authors.affiliation: Center of Scientific Excellence for Influenza Viruses, National Research Centre, Giza, Egypt.
authors.forename: Sara H
authors.initials: SH
authors.lastname: Mahmoud
authors.affiliation: Department of Chemistry, Faculty of Science, Cairo University, Cairo, Egypt.
authors.forename: Hamdi M
authors.initials: HM
authors.lastname: Hassanneen
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Webby
authors.affiliation: Center of Scientific Excellence for Influenza Viruses, National Research Centre, Giza, Egypt. Electronic address: mohamedahmedali2004@yahoo.com.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Ali
authors.affiliation: Department of Epidemiology, Human Genetics, and Environmental Sciences, University of Texas Health Sciences Center, Houston, TX, USA; Human Link, Hazmieh, Lebanon. Electronic address: ghazi@human-link.org.
authors.forename: Ghazi
authors.initials: G
authors.lastname: Kayali
mesh_terms: D000547:Amantadine / Q000494:pharmacology*; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D024882:Drug Resistance, Viral / Q000235:genetics*; D004534:Egypt / Q000453:epidemiology; D014644:Genetic Variation; D053124:Influenza A Virus, H5N1 Subtype / Q000145:classification / Q000187:drug effects / Q000235:genetics; D005585:Influenza in Birds / Q000453:epidemiology / Q000821:virology; D008826:Microbial Sensitivity Tests; D010802:Phylogeny; D011200:Poultry / Q000821:virology*; D015995:Prevalence; D012641:Selection, Genetic
chemical_list: D000998:Antiviral Agents; D000547:Amantadine
keywords: Amantadine-resistant; Egypt; H5N1 viruses