tetano
Editor, Senior Moderator
Virology. 2019 Aug 6;536:78-90. doi: 10.1016/j.virol.2019.08.005. [Epub ahead of print]
[h=1]A conserved histidine in Group-1 influenza subtype hemagglutinin proteins is essential for membrane fusion activity.[/h] Trost JF[SUP]1[/SUP], Wang W[SUP]2[/SUP], Liang B[SUP]3[/SUP], Galloway SE[SUP]2[/SUP], Agbogu E[SUP]1[/SUP], Byrd-Leotis L[SUP]4[/SUP], Steinhauer DA[SUP]5[/SUP].
[h=3]Author information[/h] 1 Department of Microbiology and Immunology, Rollins Research Center, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA, 30322, USA; Emory-UGA Center of Excellence of Influenza Research and Surveillance (CEIRS), Atlanta, GA, (NIAID Centers of Excellence for Influenza Research and Surveillance, CEIRS), USA. 2 Department of Microbiology and Immunology, Rollins Research Center, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA, 30322, USA. 3 Department of Biochemistry, Rollins Research Center, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA, 30322, USA. 4 Department of Microbiology and Immunology, Rollins Research Center, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA, 30322, USA; Emory-UGA Center of Excellence of Influenza Research and Surveillance (CEIRS), Atlanta, GA, (NIAID Centers of Excellence for Influenza Research and Surveillance, CEIRS), USA. Electronic address: labyrd@emory.edu. 5 Department of Microbiology and Immunology, Rollins Research Center, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA, 30322, USA; Emory-UGA Center of Excellence of Influenza Research and Surveillance (CEIRS), Atlanta, GA, (NIAID Centers of Excellence for Influenza Research and Surveillance, CEIRS), USA. Electronic address: dsteinh@emory.edu.
[h=3]Abstract[/h] Influenza A viruses enter host cells through the endocytic pathway, where acidification triggers conformational changes of the viral hemagglutinin (HA) to drive membrane fusion. During this process, the HA fusion peptide is extruded from its buried position in the neutral pH structure and targeted to the endosomal membrane. Conserved ionizable residues near the fusion peptide may play a role in initiating these structural rearrangements. We targeted highly conserved histidine residues in this region, at HA1 position 17 of Group-2 HA subtypes and HA2 position 111 of Group-1 HA subtypes, to determine their role in fusion activity. WT and mutant HA proteins representing several subtypes were expressed and characterized, revealing that His 111 is essential for HA functional activity of Group-1 subtypes, supporting continued efforts to target this region of the HA structure for vaccination strategies and the design of antiviral compounds.
Copyright ? 2019 Elsevier Inc. All rights reserved.
[h=4]KEYWORDS:[/h] Fusion; Hemagglutinin; Influenza; Virus entry
PMID: 31401467 DOI: 10.1016/j.virol.2019.08.005
[h=1]A conserved histidine in Group-1 influenza subtype hemagglutinin proteins is essential for membrane fusion activity.[/h] Trost JF[SUP]1[/SUP], Wang W[SUP]2[/SUP], Liang B[SUP]3[/SUP], Galloway SE[SUP]2[/SUP], Agbogu E[SUP]1[/SUP], Byrd-Leotis L[SUP]4[/SUP], Steinhauer DA[SUP]5[/SUP].
[h=3]Author information[/h] 1 Department of Microbiology and Immunology, Rollins Research Center, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA, 30322, USA; Emory-UGA Center of Excellence of Influenza Research and Surveillance (CEIRS), Atlanta, GA, (NIAID Centers of Excellence for Influenza Research and Surveillance, CEIRS), USA. 2 Department of Microbiology and Immunology, Rollins Research Center, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA, 30322, USA. 3 Department of Biochemistry, Rollins Research Center, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA, 30322, USA. 4 Department of Microbiology and Immunology, Rollins Research Center, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA, 30322, USA; Emory-UGA Center of Excellence of Influenza Research and Surveillance (CEIRS), Atlanta, GA, (NIAID Centers of Excellence for Influenza Research and Surveillance, CEIRS), USA. Electronic address: labyrd@emory.edu. 5 Department of Microbiology and Immunology, Rollins Research Center, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA, 30322, USA; Emory-UGA Center of Excellence of Influenza Research and Surveillance (CEIRS), Atlanta, GA, (NIAID Centers of Excellence for Influenza Research and Surveillance, CEIRS), USA. Electronic address: dsteinh@emory.edu.
[h=3]Abstract[/h] Influenza A viruses enter host cells through the endocytic pathway, where acidification triggers conformational changes of the viral hemagglutinin (HA) to drive membrane fusion. During this process, the HA fusion peptide is extruded from its buried position in the neutral pH structure and targeted to the endosomal membrane. Conserved ionizable residues near the fusion peptide may play a role in initiating these structural rearrangements. We targeted highly conserved histidine residues in this region, at HA1 position 17 of Group-2 HA subtypes and HA2 position 111 of Group-1 HA subtypes, to determine their role in fusion activity. WT and mutant HA proteins representing several subtypes were expressed and characterized, revealing that His 111 is essential for HA functional activity of Group-1 subtypes, supporting continued efforts to target this region of the HA structure for vaccination strategies and the design of antiviral compounds.
Copyright ? 2019 Elsevier Inc. All rights reserved.
[h=4]KEYWORDS:[/h] Fusion; Hemagglutinin; Influenza; Virus entry
PMID: 31401467 DOI: 10.1016/j.virol.2019.08.005