title: Multiple Novel Functions of Henipavirus O-glycans: The First O-glycan Functions Identified in the Paramyxovirus Family.
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.
authors: Paul G. Allen School for Global Animal Health, Washington State University, Pullman, Washington, United States of America.
authors: Jacquelyn A
authors: JA
authors: Stone
authors: Paul G. Allen School for Global Animal Health, Washington State University, Pullman, Washington, United States of America.|Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington, United States of America.
authors: Anthony V
authors: AV
authors: Nicola
authors: Department of Pathology and Laboratory Medicine, University of California, Los Angeles, California, United States of America.
authors: Linda G
authors: LG
authors: Baum
authors: Paul G. Allen School for Global Animal Health, Washington State University, Pullman, Washington, United States of America.|Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington, United States of America.
authors: Hector C
authors: HC
authors: Aguilar
mesh_terms: D002460:Cell Line; D006031:Glycosylation; D006801:Humans; D045405:Nipah Virus / Q000502:physiology*; D011134:Polysaccharides / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism; D014760:Viral Fusion Proteins / Q000378:metabolism*; D053585:Virus Attachment; D053586:Virus Internalization
chemical_list: D011134:Polysaccharides; D014759:Viral Envelope Proteins; D014760:Viral Fusion Proteins