Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P42345 (mTOR)
 26,049 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Molecular mechanisms underlying RNA splicing regulation in response to viral infection are poorly understood. Classical swine fever (CSF), one of the most economically important and highly contagious swine diseases worldwide, is caused by classical swine fever virus (CSFV). Here, we used high-throughput sequencing to obtain the digital gene expression (DGE) profile in swine umbilical vein endothelial cells (SUVEC) to identify different response genes for CSFV by using both Shimen and C strains. The numbers of clean tags obtained from the libraries of the control and both CSFV-infected libraries were 3,473,370, 3,498,355, and 3,327,493 respectively. In the comparison among the control, CSFV-C, and CSFV-Shimen groups, 644, 158, and 677 differentially expressed genes (DEGs) were confirmed in the three groups. Pathway enrichment analysis showed that many of these DEGs were enriched in spliceosome, ribosome, proteasome, ubiquitin-mediated proteolysis, cell cycle, focal adhesion, Wnt signalling pathway, etc., where the processes differ between CSFV strains of differing virulence. To further elucidate important mechanisms related to the differential infection by the CSFV Shimen and C strains, we identified four possible profiles to assess the significantly expressed genes only by CSFV Shimen or CSFV C strain. GO analysis showed that infection with CSFV Shimen and C strains disturbed 'RNA splicing' of SUVEC, resulting in differential 'gene expression' in SUVEC. Mammalian target of rapamycin (mTOR) was identified as a significant response regulator contributed to impact on SUVEC function for CSFV Shimen. This computational study suggests that CSFV of differing virulence could induce alterations in RNA splicing regulation in the host cell to change cell metabolism, resulting in acute haemorrhage and pathological damage or infectious tolerance.
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PMID:Different RNA splicing mechanisms contribute to diverse infective outcome of classical swine fever viruses of differing virulence: insights from the deep sequencing data in swine umbilical vein endothelial cells. 2733 Aug 68

Classical swine fever virus (CSFV) can utilize diverse host signaling pathways for its replication; however, the cross talk between mammalian target of rapamycin (mTOR) and CSFV remains unknown. Here, we describe the potential role of mTOR complex 1 (mTORC1) in promoting CSFV replication via virus-induced hypophosphorylation of the Akt/mTORC1/S6 pathway, especially at an early stage of viral infection. Conversely, activation of mTORC1 inhibited the replication of CSFV. Furthermore, we revealed the underlying mechanisms of mTORC1 pathway in mediating CSFV replication; in addition, our data also showed that CSFV-induced transient inhibition of mTORC1 elicited a negative feedback activation of PI3K/Akt/mTORC1pathway, likely contributing to maintain the dynamic balance between viral replication and host cell survival. This study has provided strong evidence showing how CSFV utilizes mTORC1 pathway for viral replication at an early stage in the viral replicative cycle and how the mTORC1 rescues itself by eliciting a feedback loop to limit viral replication and maintain cell survival.
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PMID:mTORC1 Negatively Regulates the Replication of Classical Swine Fever Virus Through Autophagy and IRES-Dependent Translation. 3042 32