Glycosylation of Zika Virus Is Important in Host-Virus Interaction and Pathogenesis

Routhu, Nanda Kishore; Lehoux, Sylvain D.; Rouse, Emily A.; Bidokhti, Mehdi R. M.; Giron, Leila B.; Anzurez, Alit; Reid, St Patrick; Abdel-Mohsen, Mohamed; Cummings, Richard D.; Byrareddy, Siddappa N.

Zika virus (ZIKV) is a global public health issue due to its association with severe developmental disorders in infants and neurological disorders in adults. Because 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 information about Asn-linked (N-glycans) on ZIKV E, we analyzed ZIKV E of various strains derived from different cells. ZIKV E proteins are 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 discovered that ZIKV N-glycans are important in viral pathogenesis, as mannose-specific C-type lectins DC-SIGN and L-SIGN mediate cell entry of ZIKV. Our findings represent the first detailed mapping of N-glycans on ZIKV E of various strains and their functional significance.