Mechanism of action of the suppression of influenza virus replication by Ko-Ken Tang through inhibition of the phosphatidylinositol 3-kinase/Akt signaling pathway and viral RNP nuclear export

Wu, Ming; Yen, Hung-Rong; Chang, Chia‐Lun; Peng, Tsui Yi; Hsieh, Chung Fan; Chen, Chi-Jene; Lin, Tzou Yien; Horng, Jim-Tong

doi:10.1016/j.jep.2011.01.005

Cited by 41 publications

(41 citation statements)

References 39 publications

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“…However, we were unable to detect any anti-influenza-virus activity of licorice in MDCK cells in our previous study (Wu et al, 2011). Furthermore, no reduction in viral replication was detected when the cells were pretreated with MXSGT before viral adsorption in the time-of-addition assay (lane 1, Fig.…”

Section: Discussionmentioning

confidence: 66%

“…Although both folk medicines contain ma huang and licorice, KKT does not inhibit viral entry. Two of the seven components of KKT, ma huang and cinnamon twigs (Cinnamomi ramulus), have demonstrated potent anti-influenza activity at nontoxic concentrations (Wu et al, 2011). KKT inhibits viral replication at a late stage, in which the export of viral proteins from the nucleus is blocked, implying that the inhibition of viral entry by MXSGT cannot be attributed to ma huang.…”

Section: Discussionmentioning

confidence: 99%

“…Inhibition of PI3K activity in the early stage of infection leads to a reduction in viral progeny production (Ehrhardt et al, 2007). Therefore, viral protein synthesis is reduced by the suppression of AKT phosphorylation (Shin et al, 2007;Wu et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

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Mechanism by which ma-xing-shi-gan-tang inhibits the entry of influenza virus

Hsieh

Liu

et al. 2012

Journal of Ethnopharmacology

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102

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Section: Discussionmentioning

confidence: 66%

Section: Discussionmentioning

confidence: 99%

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Mechanism by which ma-xing-shi-gan-tang inhibits the entry of influenza virus

Hsieh

Liu

et al. 2012

Journal of Ethnopharmacology

Self Cite

102

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“…Hence, it seems that M1 proteins provide a negative feedback that directs vRNPs toward nuclear export, which prevents excessive RNA production in favor of budding. Finally, the export of vRNPs itself may contribute to this regula-tion, as two independent studies found an increase in nuclear cRNA levels in the presence of export inhibitors (7,67).…”

Section: Discussionmentioning

confidence: 99%

Modeling the Intracellular Dynamics of Influenza Virus Replication To Understand the Control of Viral RNA Synthesis

Heldt

Frensing

Reichl

2012

J Virol

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bInfluenza viruses transcribe and replicate their negative-sense RNA genome inside the nucleus of host cells via three viral RNA species. In the course of an infection, these RNAs show distinct dynamics, suggesting that differential regulation takes place. To investigate this regulation in a systematic way, we developed a mathematical model of influenza virus infection at the level of a single mammalian cell. It accounts for key steps of the viral life cycle, from virus entry to progeny virion release, while focusing in particular on the molecular mechanisms that control viral transcription and replication. We therefore explicitly consider the nuclear export of viral genome copies (vRNPs) and a recent hypothesis proposing that replicative intermediates (cRNA) are stabilized by the viral polymerase complex and the nucleoprotein (NP). Together, both mechanisms allow the model to capture a variety of published data sets at an unprecedented level of detail. Our findings provide theoretical support for an early regulation of replication by cRNA stabilization. However, they also suggest that the matrix protein 1 (M1) controls viral RNA levels in the late phase of infection as part of its role during the nuclear export of viral genome copies. Moreover, simulations show an accumulation of viral proteins and RNA toward the end of infection, indicating that transport processes or budding limits virion release. Thus, our mathematical model provides an ideal platform for a systematic and quantitative evaluation of influenza virus replication and its complex regulation.

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“…It was first documented as a medicinal herb in Shen Nong Ben Cao Jing (the Divine Husbandman's Classic of Chinese Materia Medica, 206 BC-8 AD) for the treatment of febrile diseases, diabetes, dysentery and emesis. For centuries, Gegen has been prescribed in Gegen Tang, the famous decoction described in Shang Han Lun (Treatise on Fevers, 200AD), to relive fever, common cold, influenza, neck stiffness, lack of perspiration and aversion to air drafts (Qicheng, 1980;Wong et al, 2011;Wu et al, 2011). According to the literature and the clinical practice in traditional Chinese medicine, Gegen shows obvious efficacy in alleviating fever.…”

Section: Introductionmentioning

confidence: 99%