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Identification of Important N-Linked Glycosylation Sites in the Hemagglutinin Protein and Their Functional Impact on DC-SIGN Mediated Avian Influenza H5N1 Infection

  1. Author:
    Yang, Zih-Syuan
    Huang, Szu-Wei
    Wang, Wen-Hung
    Lin, Chih-Yen
    Wang, Chu-Feng
    Urbina, Aspiro Nayim
    Thitithanyanont, Arunee
    Tseng, Sung-Pin
    Lu, Po-Liang
    Chen, Yen-Hsu
    Wang, Sheng-Fan

  2. Author Address

    Kaohsiung Med Univ, Ctr Trop Med & Infect Dis, Kaohsiung 80708, Taiwan.Kaohsiung Med Univ, Dept Med Lab Sci & Biotechnol, Kaohsiung 80708, Taiwan.NCI, Model Dev Sect, Basic Res Lab, Ctr Canc Res, Frederick, MD 21702 USA.Kaohsiung Med Univ, Div Infect Dis, Dept Internal Med, Kaohsiung Med Univ Hosp, Kaohsiung 80708, Taiwan.Kaohsiung Med Univ, Clin Microbiol Lab, Dept Lab Med, Kaohsiung Med Univ Hosp, Kaohsiung 80708, Taiwan.Mahidol Univ, Dept Microbiol, Fac Sci, Bangkok 10400, Thailand.Kaohsiung Med Univ, Dept Med Res, Kaohsiung Med Univ Hosp, Kaohsiung 80708, Taiwan.
    1. Year: 2021
    2. Date: Jan
  2. Journal: International Journal of Molecular Sciences
  3. MDPI,
    1. 22
    2. 2
  5. Type of Article: Article
  6. Article Number: ARTN 743
  7. ISSN: 1422-0067
  1. Abstract:

    DC-SIGN, a C-type lectin mainly expressed in dendritic cells (DCs), has been reported to mediate several viral infections. We previously reported that DC-SIGN mediated H5N1 influenza A virus (AIVs) infection, however, the important DC-SIGN interaction with N-glycosylation sites remain unknown. This study aims to identify the optimal DC-SIGN interacting N-glycosylation sites in HA proteins of H5N1-AIVs. Results from NetNGlyc program analyzed the H5 hemagglutinin sequences of isolates during 2004-2020, revealing that seven and two conserved N-glycosylation sites were detected in HA1 and HA2 domain, respectively. A lentivirus pseudotyped A/Vietnam/1203/04 H5N1 envelope (H5N1-PVs) was generated which displayed an abundance of HA5 proteins on the virions via immuno-electron microscope observation. Further, H5N1-PVs or reverse-genetics (H5N1-RG) strains carrying a serial N-glycosylated mutation was generated by site-directed mutagenesis assay. Human recombinant DC-SIGN (rDC-SIGN) coated ELISA showed that H5N1-PVs bound to DC-SIGN, however, mutation on the N27Q, N39Q, and N181Q significantly reduced this binding (p < 0.05). Infectivity and capture assay demonstrated that N27Q and N39Q mutations significantly ameliorated DC-SIGN mediated H5N1 infection. Furthermore, combined mutations (N27Q&N39Q) significantly waned the interaction on either H5N1-PVs or -RG infection in cis and in trans (p < 0.01). This study concludes that N27 and N39 are two essential N-glycosylation contributing to DC-SIGN mediating H5N1 infection.

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External Sources

  1. View Full Text
  2. DOI: 10.3390/ijms22020743
  3. PMID: 33451024
  4. View record in Web of Science®
  5. WOS: 000611295800001

Library Notes

  1. Fiscal Year: FY2020-2021
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