The interferon antagonistic activities of the V proteins from two strains of Newcastle disease virus correlate with their known virulence properties

Abstract

SummaryNewcastle disease virus (NDV) is an avian paramyxovirus that exists as hundreds of strains with widely different virulence properties. The NDV V protein exhibits interferon (IFN) antagonistic activity, which contributes to the virulence of the virus. The IFN antagonistic activities of the V proteins from the avirulent strain La Sota and the moderately virulent strain Beaudette C (BC) were compared in an assay for the rescue of a recombinant NDV expressing the green fluorescent protein (NDV-GFP). Consistent with the virulence properties of the two viruses, the BC V protein exhibits a 4-fold greater ability to rescue replication of NDV-GFP than the La Sota V protein. Four amino acid differences in the C-terminal region of V, as well as the N-terminal region, contribute to the difference in IFN antagonistic activity between the two V proteins.Newcastle disease virus (NDV) is a member of the Paramyxoviridae family of enveloped negative-stranded RNA viruses, which also includes Sendai virus, the various parainfluenza viruses, measles virus, respiratory syncytial virus and the henipaviruses. The NDV genome contains six genes, which encode six major proteins: nucleocapsid protein (NP), phosphoprotein (P), matrix protein (M), fusion protein (F), hemagglutinin-neuraminidase protein (HN) and the large (L) polymerase (Lamb and Parks, 2007). NDV also produces the V and W proteins by RNA editing during P gene transcription. The P gene mRNA is edited by insertion of one or two additional G residues into a run of G's within the conserved editing site, thus generating the V-and W-encoding mRNAs, respectively (Steward et al., 1993 Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. , 1997). NDV is also being used as a vaccine vector (Huang et al., 2003a;Dinapoli et al., 2009) and oncolytic agent due to its ability to kill tumor cells (Elankumaran et al., 2006;Freeman et al., 2006). NIH Public AccessCleavage of the F protein precursor (F 0 ) produces the active fusion protein (Scheid and Choppin, 1974) and is the primary determinant of virulence as determined by the number of basic residues in the cleavage site (Glickman et al., 1988;Nagai et al., 1976;Toyoda et al., 1989). However, other viral proteins contribute to virulence (Panda et al., 2004;Peeters et al., 1999). Recombinant viruses lacking V have impaired growth in cell culture and embryonated chicken eggs and are highly attenuated in young chickens (Huang et al., 2003b;Mebatsion et al., 2001). These mutant viruses also exhibit increased sensitivity to exogenous interferon (IFN) (Elankumaran et al., 2006;Huang et al., 2003b). Us...

Genetic Modification of Oncolytic Newcastle Disease Virus for Cancer Therapy

“…The V protein produced via a P mRNA editing mechanism has IFN antagonistic activities (15,36), targeting MDA-5 protein (27) and inhibiting interferon regulatory factor 3 (IRF-3) activation (28). The virulent NDV Beaudette C strain has greater interferon antagonistic activities than the avirulent LaSota strain due to V protein sequence differences (14). The reduced V protein level in 73T-R-198-infected avian cells should make this virus more sensitive to innate immune responses, resulting in low chicken pathogenicity.…”

“…The P gene also encodes V and W through an RNA editing mechanism. The V protein is an IFN antagonist that contributes to viral virulence in the avian host (14,15). The fusion (F) protein is an integral glycoprotein that is syn-thesized as an inactive precursor (F0), and proteolytic cleavage of F0 into two disulfide-linked polypeptides (F1 and F2) by host cellular proteases is essential for virus infectivity and pathogenesis.…”

Virulence of newcastle disease virus: what is known so far?

“…This might correlate with their different virulence properties in vivo [89]. Previous studies using recombinant NDV that lacked the expression of the V protein already suggested that this protein plays an important role in virulence (Table 3).…”

Past and Present of Reverse Genetics in Animal Virology with Special Reference to Non-Segmented Negative Stranded RNA Viruses: a Review

“…Apart from these findings, further reports that conducted in vitro experiments on the V protein mutated viruses have shown that they have an increased rate of apoptosis (Park et al, 2003), and in vivo studies have found that the apoptotic rates corresponded to the severity of the disease caused by various strains (Harrison et al, 2011). In another study (Alamares et al, 2010), it has been reported that the V protein of a mesogenic strain, beaudette C showed a hiked anti-interferon response compared to a less virulent strain LaSota, in vitro.…”