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HIV-1 Tat Activates ERK1/2 Signaling in HBV-Infected Hepatocytes to Inhibit HBV Replication and Promote Hepatocyte Survival /

Record Type:	Language materials, printed : Monograph/item
Title/Author:	HIV-1 Tat Activates ERK1/2 Signaling in HBV-Infected Hepatocytes to Inhibit HBV Replication and Promote Hepatocyte Survival // Kyle Christopher Yeakle.
Author:	Yeakle, Kyle Christopher,
Description:	1 electronic resource (121 pages)
Notes:	Source: Dissertations Abstracts International, Volume: 86-07, Section: B.
基督教聖經之智慧書導讀 :	Globally, a chronic hepatitis B virus (HBV) infection is the leading cause of hepatocellular carcinoma (HCC). The increased risk of HCC persists in patients treated with antiviral therapy, despite suppressing viral replication. Co-infection with human immunodeficiency virus (HIV) increases the risk of developing HCC by 18-fold relative to an HBV mono-infection. Despite the clear clinical burden posed by an HIV/HBV co-infection, the mechanisms underlying the increased risk of HCC are understudied due to a lack of relevant model systems. We developed an in vitro model of HIV/HBV co-infection using Jurkat cells with inducible expression of HIV-1 Tat co-cultured with HBV-infected primary rat hepatocytes. The co-culture model was used to investigate the effect of HIV-1 Tat on HBV replication and cell survival in HBV-infected hepatocytes. Results from Jurkat-secreted Tat were complemented with purified HIV-1 Tat to determine the effect of Tat alone. Exposure to Tat significantly upregulated ERK1/2 and NF-κB signaling and cell survival in HBV-infected and uninfected hepatocytes. The activation of ERK1/2 and NF-κB signaling by Tat also inhibited HBV replication, which could be rescued by inhibition of ERK1/2 with temuterkib. Tat-dependent activation of NF-κB signaling and cell survival was also reversed by treatment with temuterkib. Tat-mediated activation of NF-κB signaling and cell survival is initiated by the TLR-4 cell surface receptor and recruitment of PKC-delta to the plasma membrane. Overall, the results of these studies indicate that Tat-mediated upregulation of ERK1/2 may promote oncogenesis and contribute to the development of HCC during an HIV/HBV co-infection by promoting cell survival.
Contained By:	Dissertations Abstracts International86-07B.
Subject:	Physiology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=31770575
ISBN:	9798302830067

HIV-1 Tat Activates ERK1/2 Signaling in HBV-Infected Hepatocytes to Inhibit HBV Replication and Promote Hepatocyte Survival /
Yeakle, Kyle Christopher,

HIV-1 Tat Activates ERK1/2 Signaling in HBV-Infected Hepatocytes to Inhibit HBV Replication and Promote Hepatocyte Survival /Kyle Christopher Yeakle. - 1 electronic resource (121 pages)

Source: Dissertations Abstracts International, Volume: 86-07, Section: B.

Globally, a chronic hepatitis B virus (HBV) infection is the leading cause of hepatocellular carcinoma (HCC). The increased risk of HCC persists in patients treated with antiviral therapy, despite suppressing viral replication. Co-infection with human immunodeficiency virus (HIV) increases the risk of developing HCC by 18-fold relative to an HBV mono-infection. Despite the clear clinical burden posed by an HIV/HBV co-infection, the mechanisms underlying the increased risk of HCC are understudied due to a lack of relevant model systems. We developed an in vitro model of HIV/HBV co-infection using Jurkat cells with inducible expression of HIV-1 Tat co-cultured with HBV-infected primary rat hepatocytes. The co-culture model was used to investigate the effect of HIV-1 Tat on HBV replication and cell survival in HBV-infected hepatocytes. Results from Jurkat-secreted Tat were complemented with purified HIV-1 Tat to determine the effect of Tat alone. Exposure to Tat significantly upregulated ERK1/2 and NF-κB signaling and cell survival in HBV-infected and uninfected hepatocytes. The activation of ERK1/2 and NF-κB signaling by Tat also inhibited HBV replication, which could be rescued by inhibition of ERK1/2 with temuterkib. Tat-dependent activation of NF-κB signaling and cell survival was also reversed by treatment with temuterkib. Tat-mediated activation of NF-κB signaling and cell survival is initiated by the TLR-4 cell surface receptor and recruitment of PKC-delta to the plasma membrane. Overall, the results of these studies indicate that Tat-mediated upregulation of ERK1/2 may promote oncogenesis and contribute to the development of HCC during an HIV/HBV co-infection by promoting cell survival.

English

ISBN: 9798302830067Subjects--Topical Terms:

197407
Physiology.
Subjects--Index Terms:

Co-infection

HIV-1 Tat Activates ERK1/2 Signaling in HBV-Infected Hepatocytes to Inhibit HBV Replication and Promote Hepatocyte Survival /
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520 $a Globally, a chronic hepatitis B virus (HBV) infection is the leading cause of hepatocellular carcinoma (HCC). The increased risk of HCC persists in patients treated with antiviral therapy, despite suppressing viral replication. Co-infection with human immunodeficiency virus (HIV) increases the risk of developing HCC by 18-fold relative to an HBV mono-infection. Despite the clear clinical burden posed by an HIV/HBV co-infection, the mechanisms underlying the increased risk of HCC are understudied due to a lack of relevant model systems. We developed an in vitro model of HIV/HBV co-infection using Jurkat cells with inducible expression of HIV-1 Tat co-cultured with HBV-infected primary rat hepatocytes. The co-culture model was used to investigate the effect of HIV-1 Tat on HBV replication and cell survival in HBV-infected hepatocytes. Results from Jurkat-secreted Tat were complemented with purified HIV-1 Tat to determine the effect of Tat alone. Exposure to Tat significantly upregulated ERK1/2 and NF-κB signaling and cell survival in HBV-infected and uninfected hepatocytes. The activation of ERK1/2 and NF-κB signaling by Tat also inhibited HBV replication, which could be rescued by inhibition of ERK1/2 with temuterkib. Tat-dependent activation of NF-κB signaling and cell survival was also reversed by treatment with temuterkib. Tat-mediated activation of NF-κB signaling and cell survival is initiated by the TLR-4 cell surface receptor and recruitment of PKC-delta to the plasma membrane. Overall, the results of these studies indicate that Tat-mediated upregulation of ERK1/2 may promote oncogenesis and contribute to the development of HCC during an HIV/HBV co-infection by promoting cell survival.
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