Mutations in the cytoplasmic domain of the Newcastle disease virus fusion protein confer hyperfusogenic phenotypes modulating viral replication and pathogenicity
Authors: Peter L Collins
Anandan Paldurai
Xiaoping Zhu
Senthilkumar Palaniyandi
Sunil K Khattar
Sweety Samal
Siba K Samal
Journal: Journal of Virology (2013)
Discipline: MICROBIOLOGY
Keywords: Newcastle disease virus; fusion protein; cytoplasmic tail; amino acids; virus replication
Affiliations: Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, Maryland, USA.

Abstract:  The Newcastle disease virus (NDV) fusion protein (F) mediates fusion of viral and host cell membranes and is a major determinant of NDV pathogenicity. In the present study, we demonstrate the effects of functional properties of F cytoplasmic tail (CT) amino acids on virus replication and pathogenesis. Out of a series of C-terminal deletions in the CT, we were able to rescue mutant viruses lacking two or four residues (rΔ2 and rΔ4). We further rescued viral mutants with individual amino acid substitutions at each of these four terminal residues (rM553A, rK552A, rT551A, and rT550A). In addition, the NDV F CT has two conserved tyrosine residues (Y524 and Y527) and a dileucine motif (LL536-537). In other paramyxoviruses, these residues were shown to affect fusion activity and are central elements in basolateral targeting. The deletion of 2 and 4 CT amino acids and single tyrosine substitution resulted in hyperfusogenic phenotypes and increased viral replication and pathogenesis. We further found that in rY524A and rY527A viruses, disruption of the targeting signals did not reduce the expression on the apical or basolateral surface in polarized Madin-Darby canine kidney cells, whereas in double tyrosine mutant, it was reduced on both the apical and basolateral surfaces. Interestingly, in rL536A and rL537A mutants, the F protein expression was more on the apical than on the basolateral surface, and this effect was more pronounced in the rL537A mutant. We conclude that these wild-type residues in the NDV F CT have an effect on regulating F protein biological functions and thus modulating viral replication and pathogenesis. 

Retracted: No

PubPeer comments:
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 February 2020 Correction. https: jvi.asm.org content 94 6 e01857-19.long  Figure 6A: Due to errors in figure assembly, the rWt and rY527A panels in the E-cadherin column (column 2, rows 2 and 4 from the top) are identical images, and the rWT panel in the DAPI column (column 1, row 2) and the Mock panel in the Merge column (column 4, row 1) are identical images. The Mock Merge, rWT E-cadherin, and rY527A E-cadherin panels from Fig. 6A should appear as shown below. (...) PUBLISHERu2019S NOTE The University of Marylandu2019s investigation determined these to be u201chonest error.u201d The journal did not notify me of this correction, although I had reported this concern to them in 2014. , 
 Figure 6A: Appears to be a mislabelling of images. 1. The rWT Merge image appears to have used the Mock E-cadherin image as the green channel rather then the rWT E-cadherin image. (circled red) 2nd image is a copy of the orignal image with the blue channel subtracted for better visualisation. ![file] ![file] ,