tetano
Editor, Senior Moderator
J Virol. 2017 May 10. pii: JVI.02511-16. doi: 10.1128/JVI.02511-16. [Epub ahead of print]
[h=1]Structural Definition of Duck MHC class I Molecules that might explain efficient CTL Immunity against Influenza A Virus.[/h] Wu Y[SUP]1[/SUP], Wang J[SUP]1[/SUP], Fan S[SUP]1[/SUP], Chen R[SUP]1[/SUP], Liu Y[SUP]1,[/SUP][SUP]2[/SUP], Zhang J[SUP]1[/SUP], Yuan H[SUP]1[/SUP], Liang R[SUP]1[/SUP], Zhang N[SUP]3[/SUP], Xia C[SUP]3,[/SUP][SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] A single dominantly expressed allele of the major histocompatibility complex class I (MHC I) may be responsible for the duck's high tolerance to the highly pathogenic (HP) influenza A virus (IAV) compared to the chicken's lower tolerance. In this study, the crystal structures of duck MHC I (Anpl-UAA*01) and duck β2m with two peptides from the H5N1 strains were determined, respectively. Two remarkable features were found to distinguish the Anpl-UAA*01 complex from other known MHC I structures. A disulfide bond formed by Cys[SUP]95[/SUP] and Cys[SUP]112[/SUP] and connecting the β5 and β6 sheets at the bottom of peptide binding groove (PBG) in Anpl-UAA*01 complex, which can enhance IAV peptides binding, was identified. Moreover, the interface area between duck MHC I and β2m was found to be larger than in other species. In addition, the two IAV peptides that display distinctive conformations in the PBG, B, and F pockets act as the primary anchor sites. 31 IAV peptides were used to verify the peptide binding motif of Anpl-UAA*01, and the results confirmed that the peptide binding motif is similar to HLA-A*0201. Basing on this motif, approximate 600 peptides from the IAV strains were partially verified as the candidate epitope-peptides for Anpl-UAA*01, which is a far greater number than that for chicken BF2*2101 and BF2*0401 molecules. Extensive IAV peptide binding should allow for ducks with this Anpl-UAA*01 haplotype to resist IAV infection.IMPORTANCE Ducks are natural reservoirs of the influenza A virus (IAV) and are more resistant to the IAV than chickens. Both ducks and chickens express only one dominant MHC I locus providing resistance to the virus. To investigate how MHC I provides IAV resistance, crystal structures of the dominantly expressed duck MHC class I (pAnpl-UAA*01) with two IAV peptides were determined. A disulfide bond was identified in the peptide binding groove that can facilitate Anpl-UAA*01 binding to IAV peptides. Anpl-UAA*01 has a much wider recognition spectrum of IAV epitope-peptides compared to chickens. The IAV peptides bound by Anpl-UAA*01 display distinctive conformations that can help induce an extensive cytotoxic T lymphocyte (CTL) response. In addition, the interface area between the duck MHC I and β2m is larger than in other species. These results indicate that HP-IAV resistance in ducks is due to extensive CTL responses induced by MHC I.
Copyright ? 2017 Wu et al.
PMID: 28490583 DOI: 10.1128/JVI.02511-16
Free full text
[h=1]Structural Definition of Duck MHC class I Molecules that might explain efficient CTL Immunity against Influenza A Virus.[/h] Wu Y[SUP]1[/SUP], Wang J[SUP]1[/SUP], Fan S[SUP]1[/SUP], Chen R[SUP]1[/SUP], Liu Y[SUP]1,[/SUP][SUP]2[/SUP], Zhang J[SUP]1[/SUP], Yuan H[SUP]1[/SUP], Liang R[SUP]1[/SUP], Zhang N[SUP]3[/SUP], Xia C[SUP]3,[/SUP][SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] A single dominantly expressed allele of the major histocompatibility complex class I (MHC I) may be responsible for the duck's high tolerance to the highly pathogenic (HP) influenza A virus (IAV) compared to the chicken's lower tolerance. In this study, the crystal structures of duck MHC I (Anpl-UAA*01) and duck β2m with two peptides from the H5N1 strains were determined, respectively. Two remarkable features were found to distinguish the Anpl-UAA*01 complex from other known MHC I structures. A disulfide bond formed by Cys[SUP]95[/SUP] and Cys[SUP]112[/SUP] and connecting the β5 and β6 sheets at the bottom of peptide binding groove (PBG) in Anpl-UAA*01 complex, which can enhance IAV peptides binding, was identified. Moreover, the interface area between duck MHC I and β2m was found to be larger than in other species. In addition, the two IAV peptides that display distinctive conformations in the PBG, B, and F pockets act as the primary anchor sites. 31 IAV peptides were used to verify the peptide binding motif of Anpl-UAA*01, and the results confirmed that the peptide binding motif is similar to HLA-A*0201. Basing on this motif, approximate 600 peptides from the IAV strains were partially verified as the candidate epitope-peptides for Anpl-UAA*01, which is a far greater number than that for chicken BF2*2101 and BF2*0401 molecules. Extensive IAV peptide binding should allow for ducks with this Anpl-UAA*01 haplotype to resist IAV infection.IMPORTANCE Ducks are natural reservoirs of the influenza A virus (IAV) and are more resistant to the IAV than chickens. Both ducks and chickens express only one dominant MHC I locus providing resistance to the virus. To investigate how MHC I provides IAV resistance, crystal structures of the dominantly expressed duck MHC class I (pAnpl-UAA*01) with two IAV peptides were determined. A disulfide bond was identified in the peptide binding groove that can facilitate Anpl-UAA*01 binding to IAV peptides. Anpl-UAA*01 has a much wider recognition spectrum of IAV epitope-peptides compared to chickens. The IAV peptides bound by Anpl-UAA*01 display distinctive conformations that can help induce an extensive cytotoxic T lymphocyte (CTL) response. In addition, the interface area between the duck MHC I and β2m is larger than in other species. These results indicate that HP-IAV resistance in ducks is due to extensive CTL responses induced by MHC I.
Copyright ? 2017 Wu et al.
PMID: 28490583 DOI: 10.1128/JVI.02511-16
Free full text