1. Academic Validation
  2. The Zika virus envelope protein glycan loop regulates virion antigenicity

The Zika virus envelope protein glycan loop regulates virion antigenicity

  • Virology. 2018 Feb:515:191-202. doi: 10.1016/j.virol.2017.12.032.
Leslie Goo 1 Christina R DeMaso 1 Rebecca S Pelc 1 Julie E Ledgerwood 2 Barney S Graham 2 Richard J Kuhn 3 Theodore C Pierson 4
Affiliations

Affiliations

  • 1 Viral Pathogenesis Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States of America.
  • 2 Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • 3 Markey Center for Structural Biology and Purdue Institute of Inflammation, Immunology and Infectious Disease, Purdue University, West Lafayette, IN, USA.
  • 4 Viral Pathogenesis Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States of America. Electronic address: piersontc@mail.nih.gov.
Abstract

Because antibodies are an important component of Flavivirus immunity, understanding the antigenic structure of flaviviruses is critical. Compared to Dengue Virus (DENV), the loop containing the single N-linked glycosylation site on Zika virus (ZIKV) envelope (E) proteins extends further towards the DII fusion loop (DII-FL) on neighboring E proteins within E dimers on mature viruses. Although ZIKV is poorly neutralized by DII-FL antibodies, we demonstrated significantly increased neutralization sensitivity of ZIKV particles incorporating the DENV glycan loop. Increased neutralization sensitivity was independent of E protein glycosylation: ZIKV lacking E protein glycans remained poorly neutralized, whereas ZIKV loop chimeras with or without an E protein glycan were potently neutralized. ZIKV particles lacking the E protein glycan were capable of infecting Raji cells expressing the lectin DC-SIGNR, suggesting the prM glycan of partially mature particles can facilitate entry. Our study provides insight into the determinants of ZIKV E protein function and antigenicity.

Keywords

Antibodies; Antigenicity; Fusion loop; Zika virus.

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