Lectin Switching During Dengue Virus Infection

Dejnirattisai, Wanwisa; Webb, Andrew I.; Chan, Vera; Jumnainsong, Amonrat; Davidson, Andrew; Mongkolsapaya, Juthathip; Screaton, Gavin

The dengue E protein has 2 potential N-linked glycosylation sites at positions 67 and 153. Cryo-electron microscopy reconstructions of dengue virus complexed to soluble DC-SIGN show interaction with the glycan at position 67 [33] . There have been several reports on the N-linked glycosylation of dengue envelope. Some reports suggest the use of both sites, whereas others suggest that only one is used [23, [34] [35] [36] . We show that in C6/36, Vero cells, and DCs either one or both sites are used for the dengue 2 serotype 16681. Although both glycosylation sites can play important roles in infectivity and viral replication, functional studies have confirmed the importance of Asn-67 for infection of DC-SIGN-expressing cells [33] . WNV E protein contains a single N-linked glycosylation site at position 154 that is absent from some virus strains [37] . Both dengue and WNV contain a single N-linked site in prM, and although prM is cleaved by furin during viral maturation, a substantial fraction of uncleaved prM is found on some dengue viruses, particularly that produced in insect cells, and such partially cleaved viruses can still be infectious. For WNV the N-linked site on prM can also mediate interaction with L-SIGN, and in common with glycan at position 154 this also showed differential specificity for L-SIGN when expressed in mammalian cell lines, perhaps mediated by the presence of N-acetylglucosamine-terminated structures [29] .