The glycosylation site in the envelope protein of West Nile virus (Sarafend) plays an important role in replication and maturation processes

Li, J.; Bhuvanakantham, Raghavan; Howe, J.; Ng, Mah-Lee

doi:10.1099/vir.0.81320-0

Cited by 41 publications

(45 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Investigations utilizing ectopic expression of WNV and TBEV prM and E proteins have ascertained that glycosylation of the E protein leads to a more rapid and efficient secretion of prM/E particles (Goto et al, 2005;Hanna et al, 2005). This enhanced secretion is observed with live DENV (Bryant et al, 2007;Lee et al, 2010) and WNV (Beasley et al, 2005;Li et al, 2006;Scherret et al, 2001) and has recently been demonstrated by our group using non-infectious C-deleted WNV replicons (Roby et al, 2013). However, an investigation utilizing live TBEV failed to demonstrate a difference in the degree of E secretion between glycosylation-mutant and WT viruses in both mammalian and tick cells (Yoshii et al, 2013).…”

Section: Glycan Modificationmentioning

confidence: 91%

“…E protein glycosylation has been linked to increased virulence in mammalian and avian models of infection (Beasley et al, 2005;Brault et al, 2011;Kariwa et al, 2013;Murata et al, 2010;Shirato et al, 2004b;Totani et al, 2011) and efficient transmission by mosquitoes (Moudy et al, 2009). Glycosylation at the E protein is proposed to potentiate these virulence phenotypes by facilitating receptor-mediated virus entry (Davis et al, 2006a, b;Martina et al, 2008;Mondotte et al, 2007;Pokidysheva et al, 2006;Tassaneetrithep et al, 2003), a greater efficiency of particle assembly and egress (Goto et al, 2005;Hanna et al, 2005;Lee et al, 2010;Li et al, 2006;Scherret et al, 2001), increased pH stability (Beasley et al, 2005;Guirakhoo et al, 1993;Lee et al, 1997) and possibly the concealment of immunogenic epitopes (Zhang et al, 2011).…”

Section: Glycan Modificationmentioning

confidence: 99%

“…Flaviviruses secrete three discrete glycoproteins from infected cells: prM (Calvert et al, 2012;Goto et al, 2005;Kim et al, 2008), E (Beasley et al, 2005;Goto et al, 2005;Hanna et al, 2005;Lee et al, 2010;Li et al, 2006;Mondotte et al, 2007;Scherret et al, 2001;Setoh et al, 2012;Winkler et al, 1987) and NS1 (Muller & Young, 2012;Muylaert et al, 1996;Somnuke et al, 2011). Asnlinked carbohydrate modifications are always present and are relatively conserved in prM and NS1 with one to three modifications in the pr portion of prM (believed to be important in protecting the fusion peptide in E during virion egress) (Goto et al, 2005;Hanna et al, 2005;Kim et al, 2008;Li et al, 2008;Mandl et al, 1988;von Lindern et al, 2006), and modification at two to three residues in NS1 (important for multimerization of soluble NS1) (Muller & Young, 2012;Muylaert et al, 1996;Somnuke et al, 2011).…”

Section: Glycan Modificationmentioning

confidence: 99%

“…Trans-membrane domains and membrane-associated helices are represented as cylinders. pH environments and the infectivity of mature virus particles (Beasley et al, 2005; Goto et al, 2005;Guirakhoo et al, 1993;Hanna et al, 2005;Lee et al, 1997Lee et al, , 2010Li et al, 2006;Mondotte et al, 2007;Scherret et al, 2001). Exploitation of these post-translational control measures has facilitated the continuing development of novel vaccines and therapeutics for use against flavivirus infections (Goto et al, 2005; Keelapang et al, 2013;Ohtaki et al, 2010;Pang et al, 2014;Roby et al, 2011Roby et al, , 2013Roby et al, , 2014Zhang et al, 2011).…”

Section: Flavivirusesmentioning

confidence: 99%

See 3 more Smart Citations

Post-translational regulation and modifications of flavivirus structural proteins

Roby

Setoh

Hall

et al. 2015

Journal of General Virology

102

View full text Add to dashboard Cite

Flaviviruses are a group of single-stranded, positive-sense RNA viruses that generally circulate between arthropod vectors and susceptible vertebrate hosts, producing significant human and veterinary disease burdens. Intensive research efforts have broadened our scientific understanding of the replication cycles of these viruses and have revealed several elegant and tightly co-ordinated post-translational modifications that regulate the activity of viral proteins. The three structural proteins in particular -capsid (C), pre-membrane (prM) and envelope (E) -are subjected to strict regulatory modifications as they progress from translation through virus particle assembly and egress. The timing of proteolytic cleavage events at the C-prM junction directly influences the degree of genomic RNA packaging into nascent virions. Proteolytic maturation of prM by host furin during Golgi transit facilitates rearrangement of the E proteins at the virion surface, exposing the fusion loop and thus increasing particle infectivity. Specific interactions between the prM and E proteins are also important for particle assembly, as prM acts as a chaperone, facilitating correct conformational folding of E. It is only once prM/E heterodimers form that these proteins can be secreted efficiently. The addition of branched glycans to the prM and E proteins during virion transit also plays a key role in modulating the rate of secretion, pH sensitivity and infectivity of flavivirus particles. The insights gained from research into post-translational regulation of structural proteins are beginning to be applied in the rational design of improved flavivirus vaccine candidates and make attractive targets for the development of novel therapeutics. FlavivirusesThe genus Flavivirus in the family Flaviviridae comprises small, enveloped viruses with non-segmented genomes consisting of single-stranded, positive-sense RNA. These RNA genomes are flanked by 59 and 39 untranslated regions (UTRs) and encode a single polyprotein that is cleaved coand post-translationally to generate between 10 and 11 viral proteins. The 59 UTR contains a type 1 m 7 GpppNm cap structure and the 39 UTR lacks a polyadenylated tail. Structural elements within the UTRs regulate genome replication, translation and host immune responses. Viral proteins are divided between structural proteins, which form the virion, and non-structural proteins, which are involved in genomic replication and modulating host immunity (Fig. 1a) (Lindenbach et al., 2007;Roby et al., 2012).Flaviviruses are maintained predominantly in natural transmission cycles between vertebrate reservoir species (normally mammalian or avian) and haematophagous arthropod vectors (mosquitoes or ticks). Notable exceptions are the viruses that are maintained solely in mosquito hosts (insectspecific flaviviruses) and viruses with no known invertebrate vector (Cook et al., 2012;Mackenzie et al., 2004). As of 2013, the International Committee on Taxonomy of Viruses has classified 53 different viral species as belonging to ...

show abstract

Section: Glycan Modificationmentioning

confidence: 91%

Section: Glycan Modificationmentioning

confidence: 99%

Section: Glycan Modificationmentioning

confidence: 99%

Section: Flavivirusesmentioning

confidence: 99%

See 2 more Smart Citations

Post-translational regulation and modifications of flavivirus structural proteins

Roby

Setoh

Hall

et al. 2015

Journal of General Virology

102

View full text Add to dashboard Cite

show abstract

“…Mutations were performed using QuikChange site-directed mutagenesis kit (Stratagene) in pGEM-T Easy vector (Promega) containing the first 1.3 kb of virus genome. The fragment was then excised with BsiWI and MluI (New England Biolabs) and ligated into the full-length cDNA of WNV (pWNV) generated earlier (Li et al, 2006). The E/prM gene amplified from pWNV was cloned into pcDNA3.1/CT-GFP (Invitrogen) (pCT-E/-prM) with a stop codon.…”

Section: Methodsmentioning

confidence: 99%

Tyrosine 78 of premembrane protein is essential for assembly of West Nile virus

Tan

Bhuvanakantham

et al. 2009

Journal of General Virology

View full text Add to dashboard Cite

Flavivirus premembrane (prM) protein plays an important role in conformational folding of the envelope (E) protein and protects it against premature fusion in acidic vesicles of the Golgi network. Currently, molecular determinants on the prM protein ectodomain which mediate critical steps during the flavivirus assembly process are poorly characterized. In this study, bioinformatics analysis and alanine scanning mutagenesis showed that the amino acid triplet valine 76, tyrosine 78 and glycine 79 is absolutely conserved among flavivirus prM ectodomains. Triple mutations engineered at these residues in prM ectodomain of West Nile virus (WNV) completely abrogated virus infectivity. Site-directed mutagenesis of prM protein revealed that tyrosine 78 of the amino acid triplet was required for virus infectivity and secretion. The mutation did not affect folding, post-translational modifications and trafficking of the prM and E proteins. Ultrastructural studies using transmission electron microscopy confirmed that virus particle formation was blocked by tyrosine 78 mutation. Specificity of assembly defect conferred by tyrosine 78 mutation was demonstrated by positive and negative trans complementation studies. Collectively, these results defined tyrosine 78 as a novel critical determinant present on prM protein ectodomain that is required for flavivirus assembly. Molecular dissection of prM protein function provides the crucial knowledge much needed in the elucidation of flavivirus particle formation.

show abstract

Carbohydrate‐Based Antiviral Vaccines

Swarts

Guo

2008

Carbohydrate‐Based Vaccines and Immunotherapies

View full text Add to dashboard Cite

The glycosylation site in the envelope protein of West Nile virus (Sarafend) plays an important role in replication and maturation processes

Cited by 41 publications

References 46 publications

Post-translational regulation and modifications of flavivirus structural proteins

Post-translational regulation and modifications of flavivirus structural proteins

Tyrosine 78 of premembrane protein is essential for assembly of West Nile virus

Carbohydrate‐Based Antiviral Vaccines

Contact Info

Product

Resources

About