Flexibility of the head-stalk linker domain of paramyxovirus HN glycoprotein is essential for triggering virus fusion

Emmanuel Adu-Gyamfi, Lori S. Kim, Theodore S. Jardetzky, Robert A. Lamb*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


The Paramyxoviridae comprise a large family of enveloped, negative-sense, single-stranded RNA viruses with significant economic and public health implications. For nearly all paramyxoviruses, infection is initiated by fusion of the viral and host cell plasma membranes in a pH-independent fashion. Fusion is orchestrated by the receptor binding protein hemagglutinin-neuraminidase (HN; also called H or G depending on the virus type) protein and a fusion (F) protein, the latter undergoing a major refolding process to merge the two membranes. Mechanistic details regarding the coupling of receptor binding to F activation are not fully understood. Here, we have identified the flexible loop region connecting the bulky enzymatically active head and the four-helix bundle stalk to be essential for fusion promotion. Proline substitution in this region of HN of parainfluenza virus 5 (PIV5) and Newcastle disease virus HN abolishes cell-cell fusion, whereas HN retains receptor binding and neuraminidase activity. By using reverse genetics, we engineered recombinant PIV5-EGFP viruses with mutations in the head-stalk linker region of HN. Mutations in this region abolished virus recovery and infectivity. In sum, our data suggest that the loop region acts as a "hinge" around which the bulky head of HN swings to-and-fro to facilitate timely HN-mediate F-triggering, a notion consistent with the stalk-mediated activation model of paramyxovirus fusion.

Original languageEnglish (US)
Pages (from-to)9172-9181
Number of pages10
JournalJournal of virology
Issue number20
StatePublished - 2016

ASJC Scopus subject areas

  • Insect Science
  • Virology
  • Microbiology
  • Immunology


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