Increased expression of T cell chemokines and their receptors in chronic hepatitis C: relationship with the histological activity of liver disease

Abstract

Intrahepatic chemokine signaling could play a key role regulating significant pathological events during chronic hepatitis C, opening new avenues for therapeutic interventions based on chemokine activities.

HIV-1 Nef Is Transferred from Expressing T Cells to Hepatocytic Cells through Conduits and Enhances HCV Replication

“…This is supported by the findings that the interaction of gp120 with CXCR4 on the surface of hepatocytes enhanced HCV replication in the replicon system, and the effect was abrogated with neutralizing antibodies against CXCR4 [25]. Interaction of Env with CXCR4 also induces apoptosis of hepatocytes together with HCV E2, and modulates signaling cascades of inflammatory cytokines involved in hepatic inflammation [26], [27], [28], [29]. However, these data need to be further confirmed, since a recent report by Iser at al [17] indicates that CXCR4, CCR5 and CD4 are not expressed in hepatic cells.…”

“…It is indeed reported that HIV-1 viral proteins are involved in regulation of HCV replication, which in turn changes the pathologic course in HCV infected patients. Specifically, Env of HIV-1 triggers signaling cascades by interacting with surface molecules, such as CXCR4 of hepatocytes, thus enhancing HCV replication [25], inducing apoptosis of hepatocytes, or causing hepatic inflammation [26], [27], [28], [29]. HIV-1 viral protein Tat, could be diffused from HIV-1 infected cells to hepatocytes and cause hepatocellular carcinoma (HCC), which is supported by a report that Tat itself enhances hepatocarcinogenesis in transgenic mice [21], [22].…”

An 85-aa segment of the GB virus type C NS5A phosphoprotein inhibits HIV-1 replication in CD4 + Jurkat T cells

“…Although measles viruses has been shown to inhibit HIV replication independent of chemokines in vitro (46), several members of the Flavivirus family (HCV, Japanese Encephalitis Virus and Dengue Virus) alter the cellular release of cytokines and chemokines (47)(48)(49). Thus, chemokine and cytokine modulation may be a common feature of Flavivirus replication, and the effects observed with GBV-C NS5A protein may be found in related viruses as well.…”

Molecular mechanisms of hepatic apoptosis

“…25, 26 HCV replication and production in infected hepatocytes can induce apoptosis and a release of inflammatory cytokines/chemokines, such as tumor necrosis factor alpha (TNF α ), TGF β , interferon-gamma (IFN γ ), interleukin 10 (IL-10), IL-12, IL-22, CCL3, CCL4, CXCR3 ligand, IP-10, CCR5 ligands, and RANTES. 27, 28, 29, 30, 31 These inflammatory cytokines/chemokines can stimulate hepatocyte apoptosis through different pathways. For instance, TNF α is a classical cytokine and its signaling pathway had been well investigated (Figure 1).…”