Identification of paramyxovirus V protein residues essential for STAT protein degradation and promotion of virus replication

Autor: Machiko Nishio, Morihiro Ito, Daniel Kolakofsky, Masato Tsurudome, Dominique Garcin, Yasuhiko Ito
Rok vydání: 2005
Předmět:
Immunology
Mutant
Molecular Sequence Data
DNA-Binding Proteins/chemistry/genetics/metabolism
Viral Proteins/chemistry/genetics/metabolism
Microbiology
Cercopithecus aethiops
Cell Line
Viral Proteins
Genes
Reporter
Virology
Cell Line
Tumor
Chlorocebus aethiops
Animals
Humans
STAT1
Amino Acid Sequence
Rubulavirus
STAT2
Mononegavirales
Vero Cells
chemistry.chemical_classification
ddc:616
Plasmids/genetics
Binding Sites
biology
Sequence Homology
Amino Acid
STAT2 Transcription Factor
biology.organism_classification
Molecular biology
Amino acid
Trans-Activators/chemistry/genetics/metabolism
DNA-Binding Proteins
Viral replication
chemistry
Insect Science
Paramyxoviridae
biology.protein
STAT protein
Paramyxoviridae/genetics/growth & development
Trans-Activators
Pathogenesis and Immunity
Sequence Alignment
HeLa Cells
Plasmids
Protein Binding
Zdroj: Journal of Virology, Vol. 79, No 13 (2005) pp. 8591-601
ISSN: 0022-538X
Popis: Some paramyxovirus V proteins induce STAT protein degradation, and the amino acids essential for this process in the human parainfluenza virus type 2 (hPIV2) V protein have been studied. Various recombinant hPIV2s and cell lines constitutively expressing various mutant V proteins were generated. We found that V proteins with replacement of Cys residues of the Cys cluster were still able to bind STATs but were unable to induce their degradation. The hPIV2 V protein binds STATs via a W-(X) 3 -W-(X) 9 -W Trp motif located just upstream of the Cys cluster. Replacements of two or more Trp residues in this motif resulted in a failure to form a V/STAT2 complex. We have also identified two Phe residues of the hPIV2 V protein that are essential for STAT degradation, namely, Phe207, lying within the Cys cluster, and Phe143, in the P/V common region of the protein. Interestingly, infection of BHK cells with hPIV2 led to the specific degradation of STAT1 and not STAT2. Other evidence for the cell species specificity of hPIV2-induced STAT degradation is presented. Finally, a V-minus hPIV2, which can express only the P protein from its P gene, was generated and partially characterized. In contrast to V-minus viruses of other paramyxovirus genera, this V-minus rubulavirus was highly debilitated, and its growth even in Vero cells was very limited. The structural rubulavirus V proteins, as expected, are thus clearly important in promoting virus growth, independent of their anti-interferon (IFN) activity. Interestingly, many of the residues that are essential for anti-IFN activity, e.g., the Cys of this cluster and Phe207 within this cluster, as well as the Trp of this motif, are also essential for promoting virus growth.
Databáze: OpenAIRE
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