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

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.

SARS-CoV-2 Spike Protein Interacts with Multiple Innate Immune Receptors

“…Densely glycosylated with multiple Asn-linked (N-glycans) and a few Ser/Thr-linked (O-glycans) 4 , 5 , the S protein of SARS-CoV-2 potentially presents ligands for a variety of innate immune receptors, including C-type lectin receptors (CLRs), that are known to bind specific glycans mostly in a Ca 2+ -dependent manner 6 , 7 . CLRs such as DC-SIGN/CD209, L-SIGN/CD209L/CLEC4M, mannose receptor/MR/MRC1/CD206, MGL/CLEC10A/CD301, and Dectin-2/CLEC6A, are highly expressed within the human immune system including monocytes, dendritic cells, and macrophages, functioning as the first-line of defense against invading viruses and pathogens 8 , 9 . As known pattern-recognition receptors, CLRs, especially DC-SIGN, can direct host immune responses against numerous pathogens in a glycan-specific manner by modulating Toll-like receptor-induced activation 10 .…”

Castanospermine reduces Zika virus infection-associated seizure by inhibiting both the viral load and inflammation in mouse models

“…However, glycosylated moieties are important for host viral interaction too. Host cell surface glycans correlated strongly with the glycomic features of ZIKV E protein indicating ZIKV uses glycosylation of its E protein to interact with host cell receptors to facilitate entry ( Routhu et al, 2019 ). High-throughput fitness profiling of ZIKV E protein reveals different roles for glycosylation during infection of mammalian and mosquito cells ( Gong et al, 2018 ).…”

Anti-Tick-Borne Encephalitis Virus Activity of Novel Uridine Glycoconjugates Containing Amide or/and 1,2,3-Triazole Moiety in the Linker Structure

“…Glycosylated E protein of flaviviruses may interact with cell surface lectins during the attachment step. The interaction of C-type lectin dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) and DC-SIGN-related protein (DC-SIGNR) with E glycoprotein of many flaviviruses: ZIKV, WNV, DENV and Japanese encephalitis virus (JEV) was reported [ 38 , 39 , 40 , 41 , 42 ]. The interaction with DC-SIGN and DC-SIGNR depends on the virus, presence of the glycan as well as on the complexity of the glycan chain.…”