UMMS Affiliation

Department of Molecular Genetics and Microbiology

Date

10-17-2008

Document Type

Article

Subjects

Animals; COS Cells; Cercopithecus aethiops; HN Protein; Newcastle disease virus; Oxidation-Reduction; Sulfhydryl Compounds; Viral Fusion Proteins; *Virus Internalization

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

Newcastle disease virus (NDV) entry into host cells is mediated by the hemagglutinin-neuraminidase (HN) and fusion (F) glycoproteins. We previously showed that production of free thiols in F protein is required for membrane fusion directed by F protein (S. Jain et al., J. Virol. 81:2328-2339, 2007). In the present study we evaluated the oxidation state of F protein in virions and virus-like particles and its relationship to activation of F protein by HN protein, F protein conformational intermediates, and virus-cell fusion. F protein, in particles, does not have free thiols, but free thiols were produced upon binding of particles to target cells. Free thiols were produced at 16 degrees C in F protein in virions bound to the target cells. They also appeared in different fusion defective mutant F proteins. Free thiols were produced in the presence of mutant HN proteins that are defective in F protein activation but are attachment competent. These results suggest that free thiols appear prior to any of the proposed major conformational changes in F protein which accompany fusion activation. These results also indicate that HN protein binding to its receptor likely facilitates the interaction between F protein and host cell isomerases, leading to reduction of disulfide bonds in F protein. Taken together, these results show that free thiols are produced in F protein at a very early stage during the onset of fusion and that the production of free thiols is required for fusion in addition to activation by HN protein.

Rights and Permissions

Citation: J Virol. 2009 Jan;83(1):241-9. Epub 2008 Oct 15. Link to article on publisher's site

DOI of Published Version

10.1128/JVI.01407-08

Related Resources

Link to Article in PubMed

Journal Title

Journal of virology

PubMed ID

18922867

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.