FKBP8 interact with classical swine fever virus NS5A protein and promote virus RNA replication

Helin Li1, Chengcheng Zhang1, Hongjie Cui1

  • 1College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, People's Republic of China.

Virus Genes
|January 11, 2016
PubMed

Insights

Classical swine fever virus (CSFV) non-structural protein 5A (NS5A) interacts with FKBP8, promoting viral RNA synthesis. FKBP8 is crucial for CSFV replication, offering potential therapeutic targets.

Area of Science:

  • Virology
  • Molecular Biology
  • Immunology

Background:

  • Classical swine fever virus (CSFV) non-structural protein 5A (NS5A) is implicated in viral replication and modulation of host responses.
  • FKBP8 is a cellular protein known to support viral replication.

Purpose of the Study:

  • To investigate the interaction between CSFV NS5A and FKBP8.
  • To elucidate the role of FKBP8 in CSFV replication.

Main Methods:

  • Coimmunoprecipitation and GST-pulldown assays to confirm NS5A-FKBP8 interaction.
  • Confocal microscopy to visualize subcellular localization of NS5A and FKBP8.
  • Functional assays involving FKBP8 overexpression and knockdown (using lentivirus-mediated shRNA) to assess impact on viral RNA synthesis and replication.

Main Results:

  • Specific interaction between CSFV NS5A and FKBP8 was demonstrated.
  • NS5A and FKBP8 were found to colocalize in the cytoplasm.
  • FKBP8 overexpression significantly enhanced CSFV RNA synthesis, while FKBP8 knockdown markedly reduced viral replication.

Conclusions:

  • FKBP8 plays a critical role in the CSFV life cycle, particularly in viral RNA replication.
  • The interaction between NS5A and FKBP8 is essential for efficient CSFV replication.
  • Targeting FKBP8 function presents a potential strategy for developing novel treatments against CSFV infection.

Related Concept Videos

Leaky Scanning02:28

Leaky Scanning

During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.9K
Inhibitors of Viral Protein Synthesis01:30

Inhibitors of Viral Protein Synthesis

Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...
20
Viruses with RNA Genomes01:29

Viruses with RNA Genomes

RNA viruses are categorized into positive-strand, negative-strand, or double-stranded groups based on their genomic structure and replication mechanisms. This classification dictates how they exploit host cellular machinery for protein synthesis and replication. Some RNA viruses also utilize reverse transcription as part of their life cycle, further diversifying their replication strategies.Positive-Strand RNA VirusesPositive-strand RNA viruses have genomes that function directly as messenger...
1.3K
Restarting Stalled Replication Forks02:37

Restarting Stalled Replication Forks

DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...
6.5K
Bacterial RNA Polymerase00:43

Bacterial RNA Polymerase

Unlike eukaryotes, bacteria use a single RNA Polymerase (RNAP) to transcribe all genes. The different subunits of bacterial RNAPhave distinct functions. The multisubunit structure of the bacterial RNAP helps the enzyme to maintain catalytic function, facilitate assembly, interact with DNA and RNA, and self-regulate its activity.
In most genes, the transcription site is a single base present upstream of the coding sequence. Though RNAP is a catalytically efficient enzyme, it does not recognize...
33.6K
Bacterial RNA Polymerase00:43

Bacterial RNA Polymerase

13.5K