Abstract
In many infectious diseases caused by either viruses or bacteria, pathogen glycoproteins play important roles during the infection cycle, ranging from entry to successful intracellular replication and host immune evasion. Dengue is no exception. Dengue virus glycoproteins, envelope protein (E) and non-structural protein 1 (NS1) are two popular sub-unit vaccine candidates. E protein on the virion surface is the major target of neutralizing antibodies. NS1 which is secreted during DENV infection has been shown to induce a variety of host responses through its binding to several host factors. However, despite their critical role in disease and protection, the glycosylated variants of these two proteins and their biological importance have remained understudied. In this review, we seek to provide a comprehensive summary of the current knowledge on protein glycosylation in DENV, and its role in virus biogenesis, host cell receptor interaction and disease pathogenesis.
Highlights
Glycosylation can be involved in receptor binding. This is exemplified by Human immunodeficiency virus (HIV) and Dengue virus (DENV) which rely on high mannose type glycosylation to bind to their mannose receptor (MR) or dendritic cell (DC)-SIGN that are present on host immune cells (Cambi and Figdor, 2003; Cambi et al, 2004)
The presence and number of NxT/S motifs vary among serotypes. ∗DENV 1 strain Nauru/West Pac/1974 (Accession no:U88535) or strain 45AZ5 (Accession no: NC_001477), DENV 2 strain SG/D2Y98P-PP1/2009 (Accession no: JF327392), DENV 3 strain GZ/10476/2012 (Accession no: KC261634) and DENV 4 isolate GZ30 (Accession no: JQ822247) are aligned against protein entries from Conserved Domain Database (CDD) or UniProt using BLAST (Basic Local Alignment Search Tool). ±The N-glycosylation site is located at residue 64 to 69 depending on the serotype
N153 deglycosylated (N153−) DENV mutant displayed reduced infectivity (10-fold lower) in both mammalian and mosquito cells compared to wild type (WT), possibly due to impaired virus entry process (Lee et al, 1997; Hacker et al, 2009), whereby loss of the N153-glycan affected the conformational stability of E proteins and led to premature exposure of the fusion peptide (Yoshii et al, 2013)
Summary
Most DENV infections are asymptomatic or remain as mild febrile illness. A classical DEN fever is diagnosed when the patient shows self-limiting high fever, headache, and muscle/joint pain 3–14 days after a mosquito bite. Ligation of Fc receptor stimulates production of Interleukin (IL) which in turn suppresses the cellular anti-viral response (Suhrbier and La Linn, 2003) These events lead to increased viral loads which are believed to correlate with disease severity (Vaughn et al, 2000). WHO recommendations have limited the use of the CYD-TDV vaccine in geographical settings with high DEN burden and in age group 9–45 years old (WHO, 2017). While this first-in-human tetravalent DEN vaccine will certainly provide a wealth of knowledge and improve our understanding of immune correlates of protection, a better vaccine is needed to protect the 3.9 billion people that are at risk of DEN infection.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
