https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3875338/
Ebolaviruksen VP35 proteiini estää PACT:in indusoiman RIG-1 aktivaation.
PACT- VP35- interaktio sensijaan vaikuttaa VP35- virusproteiinin ja viruspolymeraasin liittymistä ja sen takia vähentää viruksen RNA:n synteesiä eikä taas PACT itse vaikutu viruproteiinista VP35.
Mutual Antagonism between the Ebola Virus VP35 Protein and the RIG-I Activator PACT Determines Infection Outcome
The cytoplasmic pattern recognition receptor RIG-I is activated by viral RNA and induces type I IFN responses to control viral replication. The cellular dsRNA binding protein PACT can also activate RIG-I. To counteract innate antiviral responses, some viruses, including Ebola virus (EBOV), encode proteins that antagonize RIG-I signaling. Here, we show that EBOV VP35 inhibits PACT-induced RIG-I ATPase activity in a dose-dependent manner. The interaction of PACT with RIG-I is disrupted by wild-type VP35, but not by VP35 mutants that are unable to bind PACT. In addition, PACT-VP35 interaction impairs the association between VP35 and the viral polymerase, thereby diminishing viral RNA synthesis and modulating EBOV replication. PACT-deficient cells are defective in IFN induction and are insensitive to VP35 function. These data support a model in which the VP35-PACT interaction is mutually antagonistic and plays a fundamental role in determining the outcome of EBOV infection.
KUVA tästä tekstistä:
- Working Model for Mutual Antagonism between VP35 and PACT
EBOV
VP35 functions as an inhibitor of RIG-I signaling and as an essential
component of the viral RNA replication complex. VP35 can block either
the RNA- or the PACT-mediated activation of RIG-I, but PACT can inhibit
the RNA replication complex through interaction with VP35. Under
conditions in which VP35 levels may be limited, PACT interaction with
VP35 may slow virus replication, resulting in decreased production of
immunostimulatory viral replication products. This would allow VP35 to
sense the immune status through PACT availability and thereby regulate
replication accordingly.
GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?
- Low PACT expression is associated with Arenaviral infections.
- phenotype of our patients overlaps that of previouslyreported DYT16 patients
- this study shows that PACT is an essential coactivator of the MDA5-dependent type I IFN response to viral RNA
- High PRKRA mRNA expression is associated with colorectal cancer.
- It was established in this report that interactions between PACT, ADAR1 and HIV-1-encoded Tat protein diminish the activation of PKR in response to HIV-1 infection.
- 5 genomic variants in GSC, HOXA2 and PRKRA were identified through mutational analysis in Chinese patients with microtia.
- MicroRNA-122 Inhibits the Production of Inflammatory Cytokines by Targeting the PKR Activator PACT in Human Hepatic Stellate Cells.
- The interferon-induced protein kinase(PACT) partially rescued defects of interferon-beta1 and chemokine (C-C motif) ligand 5/RANTES (regulated on activation normal T cell expressed and secreted) induction in DDX3-knockdown HEK293 cells.
- These findings support a model in which a measles virus defective interfering RNA is sensed by PACT and RIG-I to initiate an innate antiviral response via activation of interferon-beta production.
- this study demonstrates for the first time that OV20.0 of Orf virus is also able to interact with the dsRNA binding domain of PACT and that the presence of dsRNA strengthened the interaction of these two molecules.
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