Hepatitis C Virus Core Protein and Hepatitis Activity Are Associated through Transactivation of Interleukin‐8

Hoshida, Yujin; Kato, Naoya; Yoshida, Hideo; Wang, Yue; Tanaka, Mayuko; Goto, Tadashi; Otsuka, Motoyuki; Taniguchi, Haruhito; Moriyama, Masaya; Imazeki, Fumio; Yokosuka, Osamu; Kawabe, Takao; Shiratori, Yasushi; Omata, Masao

doi:10.1086/430924

Cited by 17 publications

(10 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We propose that the regulation of CXCL-8 production by dsRNA signaling pathways represents a link between innate antiviral and inflammatory pathways. Based on previous studies (24,50), HCV NS5A and core proteins could also play a role in the CXCL-8 induction observed in the present study. In this case, the mechanisms involved could be independent of dsRNA signaling responses and involve other transcription factors such as NF-B and AP-1, reflecting the classical mode of CXCL-8 induction.…”

Section: Discussionsupporting

confidence: 77%

Regulation of CXCL-8 (Interleukin-8) Induction by Double-Stranded RNA Signaling Pathways during Hepatitis C Virus Infection

Wagoner

Austin

Green

et al. 2007

J Virol

View full text Add to dashboard Cite

Hepatitis C virus (HCV) infection induces the ␣-chemokine interleukin-8 (CXCL-8Hepatitis C virus (HCV) infects an estimated 3% or 170 million of the world's population and causes an estimated 476,000 deaths per year due to complications of end-stage liver disease (56,62). In the United States, about 1.8% of the general population or 4 million persons are infected. Of those acutely infected with HCV, approximately 85% develop chronic infection, and about 70% of these patients develop histological evidence of chronic liver disease. Moreover, viremia is not cleared in about 50% of infected patients treated with pegylated interferon (IFN)-ribavirin therapy, the current standard of care. Compounding this issue are the predictions that in the next 20 years, HCV-related complications, including hepatic decompensation, hepatocellular carcinoma, and liverrelated deaths, will increase by 106%, 81%, and 180%, respectively (12). Thus, chronic hepatitis C is a serious global medical problem necessitating effective treatment. Given the propensity of HCV for chronic infection, association with severe liver disease, and difficulty of treatment, many studies are focused on HCV-host interactions that contribute to HCV persistence and pathogenesis.

show abstract

Section: Discussionsupporting

confidence: 77%

Regulation of CXCL-8 (Interleukin-8) Induction by Double-Stranded RNA Signaling Pathways during Hepatitis C Virus Infection

Wagoner

Austin

Green

et al. 2007

J Virol

View full text Add to dashboard Cite

show abstract

“…85 In fact, activation of signalling networks downstream of TLR2 culminates in an NF-kB-dependent increase in TNF-a and direct transactivation of the IL-8 promoter resulting in increased expression of this pro-inflammatory chemokine. 86 Neutrophil chemotaxis may be enhanced further by an increase in vascular permeability mediated by TNF-a, thus contributing to increased levels of IL-8 within the liver. 75 Furthermore, the release of reactive oxygen species from granulocytes and macrophages is known to modulate the transcriptional activity of NF-kB, thereby affecting IL-8 expression.…”

Section: Pro-inflammatory Il-8 and Neutrophil Chemotaxis In Chronic Hmentioning

confidence: 99%

The role of chemokines in acute and chronic hepatitis C infection

2013

View full text Add to dashboard Cite

Hepatitis C imposes a significant burden on global healthcare. Chronic infection is associated with progressive inflammation of the liver which typically manifests in cirrhosis, organ failure and cancer. By virtue of elaborate evasion strategies, hepatitis C virus (HCV) succeeds as a persistent human virus. It has an extraordinary capacity to subvert the immune response enabling it to establish chronic infections and associated liver disease. Chemokines are low molecular weight chemotactic peptides that mediate the recruitment of inflammatory cells into tissues and back into the lymphatics and peripheral blood. Thus, they are central to the temporal and spatial distribution of effector and regulatory immune cells. The interactions between chemokines and their cognate receptors help shape the immune response and therefore, have a major influence on the outcome of infection. However, chemokines represent a target for modulation by viruses including the HCV. HCV is known to modulate chemokine expression in vitro and may therefore enable its survival by subverting the immune response in vivo through altered leukocyte chemotaxis resulting in impaired viral clearance and the establishment of chronic low-grade inflammation. In this review, the roles of chemokines in acute and chronic HCV infection are described with a particular emphasis placed on chemokine modulation as a means of immune subversion. We provide an in depth discussion of the part played by chemokines in mediating hepatic fibrosis while addressing the potential applications for these chemoattractants in prognostic medicine.

show abstract

“…The HCV core (32,58), NS4A, NS4B (35), and NS5A (6,25,37,66) have all been shown to induce CXCL8 expression in vitro. CXCL8 is elevated in the sera of HCV-infected patients (35,54,67,71) and may inhibit the antiviral activity of IFNs (35,66) and/or exacerbate inflammation (32,35). Furthermore, when mixed with T cells, HCV core protein-expressing macrophage cell lines are less effective at promoting proliferation and IFN-␥ production in T cells (45).…”

Section: Macrophages Determine Cellular and Cytokine Milieu In Hcv-anmentioning

confidence: 99%

Macrophages in Hepatitis B and Hepatitis C Virus Infections

Heydtmann

2009

J Virol

View full text Add to dashboard Cite

Hepatitis B virus (HBV) and hepatitis C virus (HCV) are major health burdens worldwide, with over 300 and 170 million people, respectively, infected. HBV, a DNA virus, and HCV, an RNA virus, are both hepatotropic, and both lead to hepatitis in many patients, with potentially fatal complications, including hepatocellular carcinoma. A high proportion of HCV-and HBV-infected patients develop chronic infections characterized by absent, weak, or narrowly focused T-cell responses (70). It is likely that early immune avoidance mechanisms contribute to the disturbed T-cell responses in combination with various other strategies reviewed elsewhere (7,28,31,36,70,82). The two viruses differ considerably in their interactions with the host immune system, but all current treatment protocols aimed at clearing either virus include alpha interferon (IFN-␣). This implies that the innate immune system is of pivotal importance in the development and maintenance of chronic infection versus viral clearance.Critical components of the innate immune response are liver macrophages. Here we highlight their key roles in both the favorable and adverse responses to HBV and HCV infections.

show abstract

Hepatitis C Virus Core Protein and Hepatitis Activity Are Associated through Transactivation of Interleukin‐8

Abstract: Differences in amino acids in the HCV core protein correlates with hepatitis activity through the modulation of IL-8 induction in HCV-infected patients.

Cited by 17 publications

References 23 publications

Regulation of CXCL-8 (Interleukin-8) Induction by Double-Stranded RNA Signaling Pathways during Hepatitis C Virus Infection

Regulation of CXCL-8 (Interleukin-8) Induction by Double-Stranded RNA Signaling Pathways during Hepatitis C Virus Infection

The role of chemokines in acute and chronic hepatitis C infection

Macrophages in Hepatitis B and Hepatitis C Virus Infections

Contact Info

Product

Resources

About