Back to Search
Start Over
Structural and Functional Characterization of the Phosphoprotein Central Domain of Spring Viremia of Carp Virus
- Source :
- J Virol
- Publication Year :
- 2020
-
Abstract
- Spring viremia of carp virus (SVCV) is a highly pathogenic Vesiculovirus in the common carp. The phosphoprotein (P protein) of SVCV is a multifunctional protein that acts as a polymerase cofactor and an antagonist of cellular interferon (IFN) response. Here, we report the 1.5-Å-resolution crystal structure of the P protein central domain (P(CD)) of SVCV (SVCV(PCD)). The P(CD) monomer consists of two β sheets, an α helix, and another two β sheets. Two P(CD) monomers pack together through their hydrophobic surfaces to form a dimer. The mutations of residues on the hydrophobic surfaces of P(CD) disrupt the dimer formation to different degrees and affect the expression of host IFN consistently. Therefore, the oligomeric state formation of the P protein of SVCV is an important mechanism to negatively regulate host IFN response. IMPORTANCE SVCV can cause spring viremia of carp with up to 90% lethality, and it is the homologous virus of the notorious vesicular stomatitis virus (VSV). There are currently no drugs that effectively cure this disease. P proteins of negative-strand RNA viruses (NSVs) play an essential role in many steps during the replication cycle and an additional role in immunosuppression as a cofactor. All P proteins of NSVs are oligomeric, but the studies on the role of this oligomerization mainly focus on the process of virus transcription or replication, and there are few studies on the role of P(CD) in immunosuppression. Here, we present the crystal structure of SVCV(PCD). A new mechanism of immune evasion is clarified by exploring the relationship between SVCV(PCD) and host IFN response from a structural biology point of view. These findings may provide more accurate target sites for drug design against SVCV and provide new insights into the function of NSV(PCD).
- Subjects :
- Protein Conformation, alpha-Helical
Immunology
Viremia
Biology
Crystallography, X-Ray
Microbiology
Virus
03 medical and health sciences
Viral Proteins
Interferon
Transcription (biology)
Virology
medicine
Animals
Polymerase
030304 developmental biology
0303 health sciences
030302 biochemistry & molecular biology
RNA
biology.organism_classification
medicine.disease
Phosphoproteins
Virus-Cell Interactions
Vesicular stomatitis virus
Insect Science
Phosphoprotein
biology.protein
Protein Conformation, beta-Strand
Rhabdoviridae
medicine.drug
Subjects
Details
- ISSN :
- 10985514
- Volume :
- 94
- Issue :
- 15
- Database :
- OpenAIRE
- Journal :
- Journal of virology
- Accession number :
- edsair.doi.dedup.....f121028205f53d49eb5aab813dcd2b9b