Glycosylation of Zika Virus is Important in Host-Virus Interaction and Pathogenic Potential

• Authors: Nanda Kishore Routhu, Emory University; Sylvain D Lehoux, Beth Israel Deaconess Medical Center; Emily A Rouse, Beth Israel Deaconess Medical Center Glycomics Core; Mehdi RM Bidokhti, University of Nebraska Medical Center; Leila B Giron, The Wistar Institute, Philadelphia; Alitzel Anzurez, The Wistar Institute, Philadelphia; St Patrick Reid, University of Nebraska Medical Center; Mohamed Abdel-Mohsen, The Wistar Institute, Philadelphia; Richard Cummings, Emory University; Siddappa Byrareddy, Emory University
• Journal Title: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
• Volume: Volume 20, Number 20
• Publisher: MDPI | 2019-10-02
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.3390/ijms20205206
• Subjects: Health Sciences, Pharmacology; Biology, Cell; Biology, Anatomy
• Keywords: Science & Technology; Life Sciences & Biomedicine; Physical Sciences; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry; host-virus interactions; Zika virus; envelope (E) protein; glycoprotein; N-linked glycans; mass spectrometry; lectin array; host cell surface glycans; N-LINKED GLYCANS; DC-SIGN; LECTIN MICROARRAY; ENVELOPE PROTEIN; STRUCTURAL BASIS; INFECTION; ARRAYS; TRANSMISSION; ASSOCIATION; EXPRESSION

Abstract

Zika virus (ZIKV) is a global public health issue due to its association with severe developmental disorders in infants and neurological disorders in adults. ZIKV uses glycosylation of its envelope (E) protein to interact with host cell receptors to facilitate entry; these interactions could also be important for designing therapeutics and vaccines. Due to a lack of proper information about Asn-linked (N-glycans) on ZIKV E, we analyzed ZIKV E of various strains derived from different cells. We found ZIKV E proteins being extensively modified with oligomannose, hybrid and complex N-glycans of a highly heterogeneous nature. Host cell surface glycans correlated strongly with the glycomic features of ZIKV E. Mechanistically, we observed that ZIKV N-glycans might play a role in viral pathogenesis, as mannose-specific C-type lectins DC-SIGN and L-SIGN mediate host cell entry of ZIKV. Our findings represent the first detailed mapping of N-glycans on ZIKV E of various strains and their functional significance.