title: Role of envelope N-linked glycosylation in Ross River virus virulence and transmission.
abstract: With an expanding geographical range and no specific treatments, human arthritogenic alphaviral disease poses a significant problem worldwide. Previous in vitro work with Ross River virus (RRV) demonstrated that alphaviral N-linked glycosylation contributes to type I IFN (IFN-αβ) induction in myeloid dendritic cells. This study further evaluated the role of alphaviral N-linked glycans in vivo, assessing the effect of glycosylation on pathogenesis in a mouse model of RRV-induced disease and on viral infection and dissemination in a common mosquito vector, Aedes vigilax. A viral mutant lacking the E1-141 glycosylation site was attenuated for virus-induced disease, with reduced myositis and higher levels of IFN-γ induction at peak disease contributing to improved viral clearance, suggesting that glycosylation of the E1 glycoprotein plays a major role in the pathogenesis of RRV. Interestingly, RRV lacking E2-200 glycan had significantly reduced replication in the mosquito vector A. vigilax, whereas loss of either of the E1 or E2-262 glycans had little effect on the competence of the mosquito vector. Overall, these results indicate that glycosylation of the E1 and E2 glycoproteins of RRV provides important determinants of viral virulence and immunopathology in the mammalian host and replication in the mosquito vector.
authors.affiliation: Faculty of Applied Science, University of Canberra, Canberra, ACT 2601, Australia.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Nelson
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast, QLD 4222, Australia.
authors.forename: Lara J
authors.initials: LJ
authors.lastname: Herrero
authors.affiliation: QIMR Berghofer Medical Research Institute, Herston, Brisbane, QLD 4006, Australia.
authors.forename: Jason A L
authors.initials: JAL
authors.lastname: Jeffery
authors.affiliation: Faculty of Applied Science, University of Canberra, Canberra, ACT 2601, Australia.|Department of Conservation Biology, Helmholtz Centre for Environmental Research, Leipzig, Germany.
authors.forename: Marion
authors.initials: M
authors.lastname: Hoehn
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast, QLD 4222, Australia.
authors.forename: Penny A
authors.initials: PA
authors.lastname: Rudd
authors.affiliation: Institute for Glycomics, Griffith University, Gold Coast, QLD 4222, Australia.
authors.forename: Aroon
authors.initials: A
authors.lastname: Supramaniam
authors.affiliation: QIMR Berghofer Medical Research Institute, Herston, Brisbane, QLD 4006, Australia.
authors.forename: Brian H
authors.initials: BH
authors.lastname: Kay
authors.affiliation: QIMR Berghofer Medical Research Institute, Herston, Brisbane, QLD 4006, Australia.|School of Biological Sciences, Monash University, Melbourne, VIC 3800, Australia.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Ryan
authors.affiliation: Faculty of Applied Science, University of Canberra, Canberra, ACT 2601, Australia.|Institute for Glycomics, Griffith University, Gold Coast, QLD 4222, Australia.
authors.forename: Suresh
authors.initials: S
authors.lastname: Mahalingam
mesh_terms: D000330:Aedes / Q000821:virology; D018354:Alphavirus Infections / Q000635:transmission / Q000821:virology*; D000818:Animals; D036022:Capsid Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D015967:Gene Expression Regulation, Viral / Q000502:physiology; D006031:Glycosylation; D007303:Insect Vectors / Q000821:virology; D051379:Mice; D009154:Mutation; D012367:RNA, Viral; D012398:Ross River virus / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D012756:Sheep / Q000097:blood; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*; D014774:Virulence; D014779:Virus Replication / Q000235:genetics
chemical_list: D036022:Capsid Proteins; C085817:E2 protein, Ross River virus; D012367:RNA, Viral; D014759:Viral Envelope Proteins