Department of Molecular Genetics and Microbiology
Animals; COS Cells; Cercopithecus aethiops; HN Protein; Newcastle disease virus; Oxidation-Reduction; Sulfhydryl Compounds; Viral Fusion Proteins; *Virus Internalization
Life Sciences | Medicine and Health Sciences
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.
DOI of Published Version
J Virol. 2009 Jan;83(1):241-9. Epub 2008 Oct 15. Link to article on publisher's site
Journal of virology
Jain, Surbhi; McGinnes, Lori; and Morrison, Trudy G., "Role of thiol/disulfide exchange in newcastle disease virus entry" (2008). Open Access Articles. 1952.