title: Functional mutations in spike glycoprotein of Zaire ebolavirus associated with an increase in infection efficiency.
abstract: Ebola virus (EBOV) is extremely virulent, and its glycoprotein is necessary for viral entry. EBOV may adapt to its new host humans during outbreaks by acquiring mutations especially in glycoprotein, which allows EBOV to spread more efficiently. To identify these evolutionary selected mutations and examine their effects on viral infectivity, we used experimental-phylogenetic-structural interdisciplinary approaches. In evolutionary analysis of all available Zaire ebolavirus glycoprotein sequences, we detected two codon sites under positive selection, which are located near/within the region critical for the host-viral membrane fusion, namely alanine-to-valine and threonine-to-isoleucine mutations at 82 (A82V) and 544 (T544I), respectively. The fine-scale transmission dynamics of EBOV Makona variants that caused the 2014-2015 outbreak showed that A82V mutant was fixed in the population, whereas T544I was not. Furthermore, pseudotype assays for the Makona glycoprotein showed that the A82V mutation caused a small increase in viral infectivity compared with the T544I mutation. These findings suggest that mutation fixation in EBOV glycoprotein may be associated with their increased infectivity levels; the mutant with a moderate increase in infectivity will fix. Our findings showed that a driving force for Ebola virus evolution via glycoprotein may be a balance between costs and benefits of its virulence.
authors.affiliation: Micro/Nano Technology Center, Tokai University, 411 Kitakaname, Hiratsuka, Kanagawa, 259-1193, Japan.
authors.forename: Mahoko Takahashi
authors.initials: MT
authors.lastname: Ueda
authors.affiliation: Department of Emerging Infectious Diseases, Institute of Tropical Medicine (NEKKEN), Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Kurosaki
authors.affiliation: Laboratory of Systems Virology, Institute for Frontier Life and Medical Sciences, Kyoto University, 53 Shogoinkawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.|CREST, Japan Science and Technology Agency, Saitama, 322-0012, Japan.
authors.forename: Taisuke
authors.initials: T
authors.lastname: Izumi
authors.affiliation: Laboratory of Systems Virology, Institute for Frontier Life and Medical Sciences, Kyoto University, 53 Shogoinkawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakano
authors.affiliation: Department of Emerging Infectious Diseases, Institute of Tropical Medicine (NEKKEN), Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan.|Graduate School of Biomedical Sciences and Program for Nurturing Global Leaders in Tropical and Emerging Communicable Diseases, Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan.
authors.forename: Olamide K
authors.initials: OK
authors.lastname: Oloniniyi
authors.affiliation: Department of Emerging Infectious Diseases, Institute of Tropical Medicine (NEKKEN), Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan.|Graduate School of Biomedical Sciences and Program for Nurturing Global Leaders in Tropical and Emerging Communicable Diseases, Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan.
authors.forename: Jiro
authors.initials: J
authors.lastname: Yasuda
authors.affiliation: Laboratory of Systems Virology, Institute for Frontier Life and Medical Sciences, Kyoto University, 53 Shogoinkawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Koyanagi
authors.affiliation: Laboratory of Systems Virology, Institute for Frontier Life and Medical Sciences, Kyoto University, 53 Shogoinkawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.|CREST, Japan Science and Technology Agency, Saitama, 322-0012, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Sato
authors.affiliation: Micro/Nano Technology Center, Tokai University, 411 Kitakaname, Hiratsuka, Kanagawa, 259-1193, Japan.|Department of Molecular Life Science, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan.
authors.forename: So
authors.initials: S
authors.lastname: Nakagawa
mesh_terms: D000072283:A549 Cells; D029043:Ebolavirus / Q000235:genetics* / Q000378:metabolism; D019143:Evolution, Molecular; D057809:HEK293 Cells; D006367:HeLa Cells; D019142:Hemorrhagic Fever, Ebola / Q000821:virology; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008958:Models, Molecular; D009154:Mutation; D017422:Sequence Analysis, DNA / Q000379:methods; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D014759:Viral Envelope Proteins; C113189:envelope glycoprotein, Ebola virus