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

PLoS Pathogens

Hector C. Aguilar¹  Linda G. Baum²  Anthony V. Nicola³  Jacquelyn A. Stone³ 

[1] Department of Pathology and Laboratory Medicine, University of California, Los Angeles, California, United States of America;Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington, United States of America;Paul G. Allen School for Global Animal Health, Washington State University, Pullman, Washington, United States of America

关键词: Virions;    Viral entry;    Membrane fusion;    Cell fusion;    Antibodies;    Flow cytometry;    Virus glycoproteins;    Glycosylation;   

DOI  :  10.1371/journal.ppat.1005445

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY