Multiple Novel Functions of Henipavirus O-glycans: The First O-glycan Functions Identified in the Paramyxovirus Family

PLoS Pathog. 2016 Feb 11;12(2):e1005445. doi: 10.1371/journal.ppat.1005445. eCollection 2016 Feb.

Abstract

O-linked glycosylation is a ubiquitous protein modification in organisms belonging to several kingdoms. Both microbial and host protein glycans are used by many pathogens for host invasion and immune evasion, yet little is known about the roles of O-glycans in viral pathogenesis. Reportedly, there is no single function attributed to O-glycans for the significant paramyxovirus family. The paramyxovirus family includes many important pathogens, such as measles, mumps, parainfluenza, metapneumo- and the deadly Henipaviruses Nipah (NiV) and Hendra (HeV) viruses. Paramyxoviral cell entry requires the coordinated actions of two viral membrane glycoproteins: the attachment (HN/H/G) and fusion (F) glycoproteins. O-glycan sites in HeV G were recently identified, facilitating use of the attachment protein of this deadly paramyxovirus as a model to study O-glycan functions. We mutated the identified HeV G O-glycosylation sites and found mutants with altered cell-cell fusion, G conformation, G/F association, viral entry in a pseudotyped viral system, and, quite unexpectedly, pseudotyped viral F protein incorporation and processing phenotypes. These are all important functions of viral glycoproteins. These phenotypes were broadly conserved for equivalent NiV mutants. Thus our results identify multiple novel and pathologically important functions of paramyxoviral O-glycans, paving the way to study O-glycan functions in other paramyxoviruses and enveloped viruses.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Line
  • Glycosylation
  • Humans
  • Nipah Virus / physiology*
  • Polysaccharides / metabolism*
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / metabolism
  • Viral Fusion Proteins / metabolism*
  • Virus Attachment
  • Virus Internalization*

Substances

  • Polysaccharides
  • Viral Envelope Proteins
  • Viral Fusion Proteins