Newcastle disease virus induces stable formation of bona fide stress granules to facilitate viral replication through manipulating host protein translation

2016 ◽  
Vol 31 (4) ◽  
pp. 1482-1493 ◽  
Author(s):  
Yingjie Sun ◽  
Luna Dong ◽  
Shengqing Yu ◽  
Xiaoxu Wang ◽  
Hang Zheng ◽  
...  
Keyword(s):  
Viral Replication ◽  
Newcastle Disease Virus ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Stress Granules ◽  
Protein Translation ◽  
Host Protein ◽  
Bona Fide ◽  
Stable Formation

Newcastle Disease Virus V protein interacts with hnRNP H1 to promote viral replication

2021 ◽  
pp. 109093
Author(s):  
Lina Tong ◽  
Zhili Chu ◽  
Xiaolong Gao ◽  
Mengqing Yang ◽  
Fathalrhman Eisa A. Adam ◽  
...  
Keyword(s):  
Viral Replication ◽  
Newcastle Disease Virus ◽  
Disease Virus ◽  
Newcastle Disease ◽  
V Protein

Ubiquitination on Lysine 247 of Newcastle Disease Virus Matrix Protein Enhances Viral Replication and Virulence by Driving Nuclear-Cytoplasmic Trafficking

2021 ◽  
Author(s):  
Tingyu Peng ◽  
Xusheng Qiu ◽  
Lei Tan ◽  
Shengqing Yu ◽  
Binghuan Yang ◽  
...  
Keyword(s):  
Viral Replication ◽  
Newcastle Disease Virus ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Nuclear Export ◽  
Viral Assembly ◽  
M Protein ◽  
Primary Function ◽  
The World ◽  
Export Signal

The Newcastle disease virus (NDV) matrix (M) protein is the pivotal element for viral assembly, budding and proliferation. It traffics through the cellular nucleus but performs its primary function in the cytoplasm. To investigate the biological importance of M’s nuclear–cytoplasmic trafficking and the mechanism involved, the regulatory motif nuclear export signal (NES) and nuclear localization signal (NLS) were deeply analyzed. Here, two types of combined NLS and NES signals were identified within NDV-M. The Herts/33-type M was found to mediate efficient nuclear export and stable virus-like particle (VLP) release, while the LaSota-type M was mostly retained in the nuclei and showed retarded VLP production. Two critical residues, 247 and 263, within the motif were identified and associated with nuclear export efficiency. We identified, for the first time, residue 247 as an important monoubiquitination site, the modification of which regulates the nuclear–cytoplasmic trafficking of NDV-M. Subsequently, mutant LaSota strains were rescued via reverse genetics, which contained either single or double amino acid substitutions that were similar to the M of Herts/33. The rescued rLaSota strains rLaSota-R247K, -S263R, and -DM (double mutation) showed about twofold higher HA titers and 10-fold higher EID 50 titers than wild-type (wt) rLaSota. Further, the MDT and ICPI values of those recombinant viruses were slightly higher than that of wt rLaSota probably due to their higher proliferation rates. Our findings contribute to a better understanding of the molecular mechanism of the replication and pathogenicity of NDV, and even those of all other paramyxoviruses. It is beneficial for the development of vaccines and therapies for paramyxoviruses. Importance Newcastle disease virus (NDV) is a pathogen that is lethal to birds and causes heavy losses in the poultry industry worldwide. The World Organization for Animal Health (OIE) ranked ND as the third most significant poultry disease and the eighth most important wildlife disease in the World Livestock Disease Atlas in 2011. The matrix (M) protein of NDV is very important for viral assembly and maturation. It is interesting that M proteins enter the cellular nucleus before performing their primary function in the cytoplasm. We found that NDV-M has a combined nuclear import and export signal. The ubiquitin modification of a lysine residue within this signal is critical for quick, efficient nuclear export and subsequent viral production. Our findings shed new light on viral replication and opens up new possibilities for therapeutics against NDV and other paramyxoviruses; furthermore, we demonstrate a novel approach to improving paramyxovirus vaccines.

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.

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