GSBS Student Publications

Title

Decreased dependence on receptor recognition for the fusion promotion activity of L289A-mutated newcastle disease virus fusion protein correlates with a monoclonal antibody-detected conformational change

UMMS Affiliation

Graduate School of Biomedical Sciences; Department of Molecular Genetics and Microbiology

Date

12-23-2004

Document Type

Article

Medical Subject Headings

Animals; Antibodies, Monoclonal; Base Sequence; COS Cells; Cricetinae; Dimerization; HN Protein; *Membrane Fusion; Molecular Sequence Data; N-Acetylneuraminic Acid; Newcastle disease virus; Protein Conformation; Receptors, Virus; Viral Fusion Proteins

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

It has been shown that the L289A-mutated Newcastle disease virus (NDV) fusion (F) protein gains the ability to promote fusion of Cos-7 cells independent of the viral hemagglutinin-neuraminidase (HN) protein and exhibits a 50% enhancement in HN-dependent fusion over wild-type (wt) F protein. Here, we show that HN-independent fusion by L289A-F is not exhibited in BHK cells or in several other cell lines. However, similar to the results in Cos-7 cells, the mutated protein plus HN does promote 50 to 70% more fusion above wt levels in all of the cell lines tested. L289A-F protein exhibits the same specificity as the wt F protein for the homologous HN protein, as well as NDV-human parainfluenza virus 3 HN chimeras. The mutated F protein promotes fusion more effectively than the wt when it is coexpressed with either the chimeras or HN proteins deficient in receptor recognition activity. In addition, its fusogenic activity is significantly more resistant to removal of sialic acid on target cells. These findings are consistent with the demonstration that L289A-F interacts more efficiently with wt and mutated HN proteins than does wt F by a cell surface coimmunoprecipitation assay. Taken together, these findings indicate that L289A-F promotes fusion by a mechanism analogous to that of the wt protein with respect to the HN-F interaction but is less dependent on the attachment activity of HN. The phenotype of the mutated F protein correlates with a conformational change in the protein detectable by two different monoclonal antibodies. This conformational change may reflect a destabilization of F structure induced by the L289A substitution, which may in turn indicate a lower energy requirement for fusion activation.

Rights and Permissions

Citation: J Virol. 2005 Jan;79(2):1180-90. Link to article on publisher's site

Related Resources

Link to article in PubMed

Journal Title

Journal of virology

PubMed ID

15613345