About: BX-795 inhibits HSV-1 and HSV-2 replication by blocking the JNK/p38 pathways without interfering with PDK1 activity in host cells

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About: BX-795 inhibits HSV-1 and HSV-2 replication by blocking the JNK/p38 pathways without interfering with PDK1 activity in host cells Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	BX-795 inhibits HSV-1 and HSV-2 replication by blocking the JNK/p38 pathways without interfering with PDK1 activity in host cells
Creator	Qiu, Min Song, Hong-Yong Wu, Zhi-Wei Zheng, Nan Li, Yan-Lei Song, Si-Wei Su, Ai-Rong Wang, Xiao-Hui Xu, Wen-Tao
Source	Medline; PMC
abstract	BX-795 is an inhibitor of 3-phosphoinositide-dependent kinase 1 (PDK1), but also a potent inhibitor of the IKK-related kinase, TANKbinding kinase 1 (TBK1) and IKKɛ. In this study we attempted to elucidate the molecular mechanism(s) underlying the inhibition of BX-795 on Herpes simplex virus (HSV) replication. HEC-1-A or Vero cells were treated with BX-795 and infected with HSV-1 or HSV-2 for different periods. BX-795 (3.125-25 μmol/L) dose-dependently suppressed HSV-2 replication, and displayed a low cytotoxicity to the host cells. BX-795 treatment dose-dependently suppressed the expression of two HSV immediate-early (IE) genes (ICP0 and ICP27) and the late gene (gD) at 12 h postinfection. HSV-2 infection resulted in the activation of PI3K and Akt in the host cells, and BX-795 treatment inhibited HSV-2-induced Akt phosphorylation and activation. However, the blockage of PI3K/Akt/mTOR with LY294002 and rapamycin did not affect HSV-2 replication. HSV-2 infection increased the phosphorylation of JNK and p38, and reduced ERK phosphorylation at 8 h postinfection in the host cells; BX-795 treatment inhibited HSV-2-induced activation of JNK and p38 MAP kinase as well as the phosphorylation of c-Jun and ATF-2, the downstream targets of JNK and p38 MAP kinase. Furthermore, SB203580 (a p38 inhibitor) or SP600125 (a JNK inhibitor) dose-dependently inhibited the viral replication in the host cells, whereas PD98059 (an ERK inhibitor) was not effective. Moreover, BX-795 blocked PMA-stimulated c-Jun activation as well as HSV-2-mediated c-Jun nuclear translocation. BX-795 dose-dependently inhibited HSV-2, PMA, TNF-α-stimulated AP-1 activation, but not HSV-induced NF-κB activation. Overexpression of p38/JNK attenuated the inhibitory effect of BX-795 on HSV replication. BX-795 completely blocked HSV-2-induced MKK4 phosphorylation, suggesting that BX-795 acting upstream of JNK and p38 MAP kinase. In conclusion, this study identifies the anti-HSV activity of BX-795 and its targeting of the JNK/p38 MAP kinase pathways in host cells.
has issue date	2017-01-23(xsd:dateTime)
bibo:doi	10.1038/aps.2016.160
bibo:pmid	28112176
has license	bronze-oa
sha1sum (hex)	21cc67d7621201e72ce2fa654581cba5b4d301c9
schema:url	https://doi.org/10.1038/aps.2016.160
resource representing a document's title	BX-795 inhibits HSV-1 and HSV-2 replication by blocking the JNK/p38 pathways without interfering with PDK1 activity in host cells
has PubMed Central identifier	PMC5342671
has PubMed identifier	28112176
schema:publication	Acta Pharmacologica Sinica
resource representing a document's body	covid:21cc67d7621201e72ce2fa654581cba5b4d301c9#body_text
is schema:about of	named entity 'REPLICATION' named entity 'ATTEMPTED' named entity 'ATTENUATED' named entity 'NUCLEAR TRANSLOCATION' named entity '283' named entity '28S' named entity 'MAP KINASE' named entity 'LATE' named entity 'DIFFERENT' named entity 'IKK-RELATED KINASE' named entity 'VERO CELLS' named entity 'HSV' named entity '125' named entity 'BAB' named entity 'MEDIATED' named entity 'ATF-2' named entity 'GENE' named entity 'PI3K' named entity 'BUT' named entity 'REDUCED' named entity 'DISPLAYED' named entity 'ERK' named entity 'STIMULATED' named entity 'HSV-2 INFECTION' named entity 'MKK4' named entity 'STUDY' named entity 'INHIBITED' named entity 'INTERFERING' named entity 'BLOCKAGE' named entity 'DID' named entity 'PMA' named entity 'INHIBITION' named entity 'HOST CELLS' named entity 'COMPLETELY' named entity 'KINASE' named entity 'CYTOTOXICITY' named entity 'SUPPRESSED' named entity 'BX-795' named entity 'IKK' named entity 'HEC-1-A' named entity 'EXPRESSION' named entity 'JNK INHIBITOR' named entity 'DOWNSTREAM' named entity 'UNDERLYING' named entity 'AKT' named entity 'P38 MAP KINASE' named entity 'INHIBITOR' named entity 'GENES' named entity 'AP-1 ACTIVATION' named entity 'INFECTED' named entity '28A' named entity 'BX-795' named entity 'BLOCKING' named entity 'HSV-2' named entity 'PATHWAYS' named entity 'PDK1' named entity 'TARGETING' named entity 'TREATMENT' named entity 'CONCLUSION' named entity 'TREATED WITH' named entity 'TARGETS' named entity 'INDUCED' named entity 'AFFECT' named entity 'BLOCKED' named entity 'EARLY' named entity 'HSV-2' named entity 'DOSE' named entity 'REPLICATION' named entity 'HOST CELLS' named entity 'PATHWAYS' named entity 'OVEREXPRESSION' named entity 'JNK' named entity 'HSV-1'

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