Evolution of H5-Type Avian Influenza A Virus Towards Mammalian Tropism in Egypt, 2014 to 2015

Highly pathogenic avian influenza viruses (HPAIV) of the H5-subtype have circulated continuously in Egypt since 2006, resulting in numerous poultry outbreaks and considerable sporadic human infections. The extensive circulation and wide spread of these viruses in domestic poultry have resulted in va...

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Main Authors: Sara Hussein Mahmoud, Ahmed Mostafa, Rabeh El-Shesheny, Mohamed Zakaraia Seddik, Galal Khalafalla, Mahmoud Shehata, Ahmed Kandeil, Stephan Pleschka, Ghazi Kayali, Richard Webby, Veljko Veljkovic, Mohamed Ahmed Ali
Format: Article
Language:English
Published: MDPI AG 2019-11-01
Series:Pathogens
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Online Access:https://www.mdpi.com/2076-0817/8/4/224
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author Sara Hussein Mahmoud
Ahmed Mostafa
Rabeh El-Shesheny
Mohamed Zakaraia Seddik
Galal Khalafalla
Mahmoud Shehata
Ahmed Kandeil
Stephan Pleschka
Ghazi Kayali
Richard Webby
Veljko Veljkovic
Mohamed Ahmed Ali
author_facet Sara Hussein Mahmoud
Ahmed Mostafa
Rabeh El-Shesheny
Mohamed Zakaraia Seddik
Galal Khalafalla
Mahmoud Shehata
Ahmed Kandeil
Stephan Pleschka
Ghazi Kayali
Richard Webby
Veljko Veljkovic
Mohamed Ahmed Ali
author_sort Sara Hussein Mahmoud
collection DOAJ
description Highly pathogenic avian influenza viruses (HPAIV) of the H5-subtype have circulated continuously in Egypt since 2006, resulting in numerous poultry outbreaks and considerable sporadic human infections. The extensive circulation and wide spread of these viruses in domestic poultry have resulted in various evolutionary changes with a dramatic impact on viral transmission ability to contact mammals including humans. The transmitted viruses are either (1) adapted well enough in their avian hosts to readily infect mammals, or (2) adapted in the new mammalian hosts to improve their fitness. In both cases, avian influenza viruses (AIVs) acquire various host-specific adaptations. These adaptive variations are not all well-known or thoroughly characterized. In this study, a phylogenetic algorithm based on the informational spectrum method, designated hereafter as ISM, was applied to analyze the affinity of H5-type HA proteins of Egyptian AIV isolates (2006−2015) towards human-type cell receptors. To characterize AIV H5-HA proteins displaying high ISM values reflecting an increased tendency of the HA towards human-type receptors, recombinant IV expressing monobasic, low pathogenic (LP) H5-HA versions in the background of the human influenza virus A/PR/8/1934(H1N1) (LP 7+1), were generated. These viruses were compared with a LP 7+1 expressing a monobasic H5-HA from a human origin virus isolate (human LP-7271), for their receptor binding specificity (ISM), in vitro replication efficiency and in vivo pathogenicity in mammals. Interestingly, using ISM analysis, we identified a LP 7+1 virus (LP-S10739C) expressing the monobasic H5-HA of AIV A/Chicken/Egypt/S10739C/2015(H5N1) that showed high affinity towards human-type receptors. This in silico prediction was reflected by a higher in vitro replication efficiency in mammalian cell cultures and a higher virulence in mice as compared with LP-7271. Sequence comparison between the LP-S10739C and the LP-7271 H5-HA, revealed distinct amino acid changes. Their contribution to the increased mammalian receptor propensity of LP-S10739C demands further investigation to better deduce the molecular determinant behind the reported high morbidity of 2014 to 2015 HPAI H5N1 virus in humans in Egypt. This study provides insights into the evolution of Egyptian H5 HPAIVs and highlights the need to identify the viral evolution in order to recognize emerging AIV with the potential to threaten human and animal populations.
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spelling doaj.art-75ed70f7c58342dfaf2185d614d825252022-12-22T02:10:02ZengMDPI AGPathogens2076-08172019-11-018422410.3390/pathogens8040224pathogens8040224Evolution of H5-Type Avian Influenza A Virus Towards Mammalian Tropism in Egypt, 2014 to 2015Sara Hussein Mahmoud0Ahmed Mostafa1Rabeh El-Shesheny2Mohamed Zakaraia Seddik3Galal Khalafalla4Mahmoud Shehata5Ahmed Kandeil6Stephan Pleschka7Ghazi Kayali8Richard Webby9Veljko Veljkovic10Mohamed Ahmed Ali11Center of Scientific Excellence for Influenza Viruses, National Research Centre (NRC), Dokki, Giza 12622, EgyptCenter of Scientific Excellence for Influenza Viruses, National Research Centre (NRC), Dokki, Giza 12622, EgyptCenter of Scientific Excellence for Influenza Viruses, National Research Centre (NRC), Dokki, Giza 12622, EgyptMicrobiology Department, Faculty of Agriculture, Cairo University, Giza 12613, EgyptMicrobiology Department, Faculty of Agriculture, Cairo University, Giza 12613, EgyptCenter of Scientific Excellence for Influenza Viruses, National Research Centre (NRC), Dokki, Giza 12622, EgyptCenter of Scientific Excellence for Influenza Viruses, National Research Centre (NRC), Dokki, Giza 12622, EgyptInstitute of Medical Virology, Justus Liebig University (JLU) Giessen, Schubertstrasse 81, 35392 Giessen, GermanyDepartment of Epidemiology, Human Genetics, and Environmental Sciences, University of Texas, Houston, TX 77030, USADepartment of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN 38105, USABiomed Protection, Galveston, TX 77550, USACenter of Scientific Excellence for Influenza Viruses, National Research Centre (NRC), Dokki, Giza 12622, EgyptHighly pathogenic avian influenza viruses (HPAIV) of the H5-subtype have circulated continuously in Egypt since 2006, resulting in numerous poultry outbreaks and considerable sporadic human infections. The extensive circulation and wide spread of these viruses in domestic poultry have resulted in various evolutionary changes with a dramatic impact on viral transmission ability to contact mammals including humans. The transmitted viruses are either (1) adapted well enough in their avian hosts to readily infect mammals, or (2) adapted in the new mammalian hosts to improve their fitness. In both cases, avian influenza viruses (AIVs) acquire various host-specific adaptations. These adaptive variations are not all well-known or thoroughly characterized. In this study, a phylogenetic algorithm based on the informational spectrum method, designated hereafter as ISM, was applied to analyze the affinity of H5-type HA proteins of Egyptian AIV isolates (2006−2015) towards human-type cell receptors. To characterize AIV H5-HA proteins displaying high ISM values reflecting an increased tendency of the HA towards human-type receptors, recombinant IV expressing monobasic, low pathogenic (LP) H5-HA versions in the background of the human influenza virus A/PR/8/1934(H1N1) (LP 7+1), were generated. These viruses were compared with a LP 7+1 expressing a monobasic H5-HA from a human origin virus isolate (human LP-7271), for their receptor binding specificity (ISM), in vitro replication efficiency and in vivo pathogenicity in mammals. Interestingly, using ISM analysis, we identified a LP 7+1 virus (LP-S10739C) expressing the monobasic H5-HA of AIV A/Chicken/Egypt/S10739C/2015(H5N1) that showed high affinity towards human-type receptors. This in silico prediction was reflected by a higher in vitro replication efficiency in mammalian cell cultures and a higher virulence in mice as compared with LP-7271. Sequence comparison between the LP-S10739C and the LP-7271 H5-HA, revealed distinct amino acid changes. Their contribution to the increased mammalian receptor propensity of LP-S10739C demands further investigation to better deduce the molecular determinant behind the reported high morbidity of 2014 to 2015 HPAI H5N1 virus in humans in Egypt. This study provides insights into the evolution of Egyptian H5 HPAIVs and highlights the need to identify the viral evolution in order to recognize emerging AIV with the potential to threaten human and animal populations.https://www.mdpi.com/2076-0817/8/4/224ism analysisevolutionhuman-type receptor
spellingShingle Sara Hussein Mahmoud
Ahmed Mostafa
Rabeh El-Shesheny
Mohamed Zakaraia Seddik
Galal Khalafalla
Mahmoud Shehata
Ahmed Kandeil
Stephan Pleschka
Ghazi Kayali
Richard Webby
Veljko Veljkovic
Mohamed Ahmed Ali
Evolution of H5-Type Avian Influenza A Virus Towards Mammalian Tropism in Egypt, 2014 to 2015
Pathogens
ism analysis
evolution
human-type receptor
title Evolution of H5-Type Avian Influenza A Virus Towards Mammalian Tropism in Egypt, 2014 to 2015
title_full Evolution of H5-Type Avian Influenza A Virus Towards Mammalian Tropism in Egypt, 2014 to 2015
title_fullStr Evolution of H5-Type Avian Influenza A Virus Towards Mammalian Tropism in Egypt, 2014 to 2015
title_full_unstemmed Evolution of H5-Type Avian Influenza A Virus Towards Mammalian Tropism in Egypt, 2014 to 2015
title_short Evolution of H5-Type Avian Influenza A Virus Towards Mammalian Tropism in Egypt, 2014 to 2015
title_sort evolution of h5 type avian influenza a virus towards mammalian tropism in egypt 2014 to 2015
topic ism analysis
evolution
human-type receptor
url https://www.mdpi.com/2076-0817/8/4/224
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