Abstract
Paramyxoviridae consist of a large family of enveloped, negative-sense, nonsegmented single-stranded RNA viruses that account for a significant number of human and animal diseases. The fusion process for nearly all paramyxoviruses involves the mixing of the host cell plasma membrane and the virus envelope in a pH-independent fashion. Fusion is orchestrated via the concerted action of two surface glycoproteins: an attachment protein called hemagglutinin-neuraminidase (HN [also called H or G depending on virus type and substrate]), which acts as a receptor binding protein, and a fusion (F) protein, which undergoes a major irreversible refolding process to merge the two membranes. Recent biochemical evidence suggests that receptor binding by HN is dispensable for cell-cell fusion. However, factors that influence the stability and/or conformation of the HN 4-helix bundle (4HB) stalk have not been studied. Here, we used oxidative cross-linking as well as functional assays to investigate the role of the structurally unresolved membrane-proximal stalk region (MPSR) (residues 37 to 58) of HN in the context of headless and fulllength HN membrane fusion promotion. Our data suggest that the receptor binding head serves to stabilize the stalk to regulate fusion. Moreover, we found that the MPSR of HN modulates receptor binding and neuraminidase activity without a corresponding regulation of F triggering.
Original language | English (US) |
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Pages (from-to) | 7778-7788 |
Number of pages | 11 |
Journal | Journal of virology |
Volume | 90 |
Issue number | 17 |
DOIs | |
State | Published - 2016 |
Funding
This research was supported in part by National Institutes of Health Research grants R01 AI 23173 (to R.A.L.) and R01 GM 61050 (to T.S.J.). R.A.L. is an Investigator of the Howard Hughes Medical Institute. E.A.-G. was supported by the UNCF-Merck Postdoctoral Science Research Fellowship. This work, including the efforts of ROBERT A. LAMB, was funded by Howard Hughes Medical Institute (HHMI) (69-100). This work, including the efforts of Theodore Jardetsky and ROBERT A. LAMB, was funded by HHS|DHHSOffice of the Secretary (OS) (R01 GM-61050). This work, including the efforts of Theodore Jardetsky and ROBERT A. LAMB, was funded by HHS | DHHS Office of the Secretary (OS) (R01-AI-23173).
ASJC Scopus subject areas
- Insect Science
- Virology
- Microbiology
- Immunology