scholarly journals Two single amino acid substitutions in the intervening region of Newcastle disease virus HN protein attenuate viral replication and pathogenicity

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Bin Liu ◽  
Yanhong Ji ◽  
Zhongqing Lin ◽  
Yuguang Fu ◽  
Rihab Muhammad Dafallah ◽  
...  
Keyword(s):  
Amino Acid ◽  
Viral Replication ◽  
Newcastle Disease Virus ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Single Amino Acid ◽  
Amino Acid Substitutions

scholarly journals A single amino acid change, Q114R, in the cleavage-site sequence of Newcastle disease virus fusion protein attenuates viral replication and pathogenicity

2011 ◽  
Vol 92 (10) ◽  
pp. 2333-2338 ◽  
Author(s):  
Sweety Samal ◽  
Sachin Kumar ◽  
Sunil K. Khattar ◽  
Siba K. Samal
Keyword(s):  
Amino Acid ◽  
Viral Replication ◽  
Newcastle Disease Virus ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Cleavage Site ◽  
Single Amino Acid ◽  
Protein Cleavage ◽  
F Protein ◽  
Glutamine Residue

A key determinant of Newcastle disease virus (NDV) virulence is the amino acid sequence at the fusion (F) protein cleavage site. The NDV F protein is synthesized as an inactive precursor, F0, and is activated by proteolytic cleavage between amino acids 116 and 117 to produce two disulfide-linked subunits, F1 and F2. The consensus sequence of the F protein cleavage site of virulent [112(R/K)-R-Q-(R/K)-R↓F-I118] and avirulent [112(G/E)-(K/R)-Q-(G/E)-R↓L-I118] strains contains a conserved glutamine residue at position 114. Recently, some NDV strains from Africa and Madagascar were isolated from healthy birds and have been reported to contain five basic residues (R-R-R-K-R↓F-I/V or R-R-R-R-R↓F-I/V) at the F protein cleavage site. In this study, we have evaluated the role of this conserved glutamine residue in the replication and pathogenicity of NDV by using the moderately pathogenic Beaudette C strain and by making Q114R, K115R and I118V mutants of the F protein in this strain. Our results showed that changing the glutamine to a basic arginine residue reduced viral replication and attenuated the pathogenicity of the virus in chickens. The pathogenicity was further reduced when the isoleucine at position 118 was substituted for valine.

scholarly journals The Viral Replication Complex Is Associated with the Virulence of Newcastle Disease Virus

2010 ◽  
Vol 84 (19) ◽  
pp. 10113-10120 ◽  
Author(s):  
J. C. F. M. Dortmans ◽  
P. J. M. Rottier ◽  
G. Koch ◽  
B. P. H. Peeters
Keyword(s):  
Amino Acid ◽  
Viral Replication ◽  
Newcastle Disease Virus ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Replication Complex ◽  
Virulent Strains ◽  
Viral Replication Complex

ABSTRACT Virulent strains of Newcastle disease virus ([NDV] also known as avian paramyxovirus type 1) can be discriminated from low-virulence strains by the presence of multiple basic amino acid residues at the proteolytic cleavage site of the fusion (F) protein. However, some NDV variants isolated from pigeons (pigeon paramyxovirus type 1 [PPMV-1]) have low levels of virulence, despite the fact that their F protein cleavage sites contain a multibasic amino acid sequence and have the same functionality as that of virulent strains. To determine the molecular basis of this discrepancy, we examined the role of the internal proteins in NDV virulence. Using reverse genetics, the genes encoding the nucleoprotein (NP), phosphoprotein (P), matrix protein (M), and large polymerase protein (L) were exchanged between the nonvirulent PPMV-1 strain AV324 and the highly virulent NDV strain Herts. Recombinant viruses were evaluated for their pathogenicities and replication levels in day-old chickens, and viral genome replication and plaque sizes were examined in cell culture monolayers. We also tested the contributions of the individual NP, P, and L proteins to the activity of the viral replication complex in an in vitro replication assay. The results showed that the replication proteins of Herts are more active than those of AV324 and that the activity of the viral replication complex is directly related to virulence. Although the M protein affected viral replication in vitro, it had only a minor effect on virulence.

scholarly journals A single amino acid mutation, R42A, in the Newcastle disease virus matrix protein abrogates its nuclear localization and attenuates viral replication and pathogenicity

2014 ◽  
Vol 95 (5) ◽  
pp. 1067-1073 ◽  
Author(s):  
Zhiqiang Duan ◽  
Juan Li ◽  
Jie Zhu ◽  
Jian Chen ◽  
Haixu Xu ◽  
...  
Keyword(s):  
Viral Replication ◽  
Newcastle Disease Virus ◽  
Disease Virus ◽  
Nuclear Localization ◽  
Newcastle Disease ◽  
Matrix Protein ◽  
M Protein ◽  
Single Amino Acid ◽  
Basic Residue

The Newcastle disease virus (NDV) matrix (M) protein is a highly basic and nucleocytoplasmic shuttling viral protein. Previous study has demonstrated that the N-terminal 100 aa of NDV M protein are somewhat acidic overall, but the remainder of the polypeptide is strongly basic. In this study, we investigated the role of the N-terminal basic residues in the subcellular localization of M protein and in the replication and pathogenicity of NDV. We found that mutation of the basic residue arginine (R) to alanine (A) at position 42 disrupted M’s nuclear localization. Moreover, a recombinant virus with R42A mutation in the M protein reduced viral replication in DF-1 cells and attenuated the virulence and pathogenicity of the virus in chickens. This is the first report to show that a basic residue mutation in the NDV M protein abrogates its nuclear localization and attenuates viral replication and pathogenicity.

scholarly journals Amino Acid Substitutions in the F-Specific Domain in the Stalk of the Newcastle Disease Virus HN Protein Modulate Fusion and Interfere with Its Interaction with the F Protein

2004 ◽  
Vol 78 (23) ◽  
pp. 13053-13061 ◽  
Author(s):  
Vanessa R. Melanson ◽  
Ronald M. Iorio
Keyword(s):  
Amino Acid ◽  
Newcastle Disease Virus ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Amino Acid Substitutions ◽  
Globular Domain ◽  
Viral Glycoprotein ◽  
Specific Domain ◽  
F Protein ◽  
Heptad Repeats

ABSTRACT The hemagglutinin-neuraminidase (HN) protein of Newcastle disease virus mediates attachment to sialic acid receptors, as well as cleavage of the same moiety. HN also interacts with the other viral glycoprotein, the fusion (F) protein, to promote membrane fusion. The ectodomain of the HN spike consists of a stalk and a terminal globular head. The most conserved part of the stalk consists of two heptad repeats separated by a nonhelical intervening region (residues 89 to 95). Several amino acid substitutions for a completely conserved proline residue in this region not only impair fusion and the HN-F interaction but also decrease neuraminidase activity in the globular domain, suggesting that the substitutions may alter HN structure. Substitutions for L94 also interfere with fusion and the HN-F interaction but have no significant effect on any other HN function. Amino acid substitutions at other positions in the intervening region also modulate only fusion. In all cases, diminished fusion correlates with a decreased ability of the mutated HN protein to interact with F at the cell surface. These findings indicate that the intervening region is critical to the role of HN in the promotion of fusion and may be directly involved in its interaction with the homologous F protein.

Sign in / Sign up

Export Citation Format

Share Document