Role of chemokines and their receptors in viral persistence and liver damage during chronic hepatitis C virus infection

Larrubia, J.R.; Benito-Martínez, Selma; Calvino, Miryam; Sanz-de-Villalobos, E.; Parra-Cid, T.

doi:10.3748/wjg.14.7149

Cited by 123 publications

(118 citation statements)

References 80 publications

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“…These findings suggest that a large number of inflammatory pathways and mechanisms are operant in patients destined not to survive PALF, leading to a state of selfsustaining or self-propagating inflammation driven by both innate and T cell-dependent mechanisms. reported in liver failure 27,28 , and circulating levels of both chemokines have been implicated in chronic hepatitis C 29 . We have shown that MCP-1 is a central node in hepatocyte inflammatory responses to stress, a role perhaps related to the ability of circulating MCP-1 levels to segregate outcomes in human blunt trauma 15 .…”

Section: Discussionmentioning

confidence: 99%

Data-Driven Modeling for Precision Medicine in Pediatric Acute Liver Failure

Zamora

Vodovotz

et al. 2016

Mol Med

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Absence of early outcome biomarkers for Pediatric Acute Liver Failure (PALF) hinders medical and liver transplant decisions. We sought to define dynamic interactions among circulating inflammatory mediators to gain insights into PALF outcome sub-groups. Serum samples from 101 participants in the PALF study, collected over the first 7 days following enrollment, were assayed for 27 inflammatory mediators.Outcomes (Spontaneous survivors [S, n=61], Non-survivors [NS, n=12], and liver transplant patients [LTx, n=28]) were assessed at 21 days post-enrollment. Dynamic interrelations among mediators were defined using data-driven algorithms. Dynamic Bayesian Network inference identified a common network motif with HMGB1 as a central node in all patient sub-groups. The networks in S and LTx were similar, and differed from NS. Dynamic Network Analysis suggested similar dynamic connectivity in S and LTx, but a more highly-interconnected network in NS that increased with time. A Dynamic Robustness Index calculated to quantify how inflammatory network connectivity changes as a function of correlation stringency differentiated all three patient sub-groups. Our results suggest that increasing inflammatory network connectivity is associated with non-survival in PALF, and may ultimately lead to better patient outcome stratification.

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Section: Discussionmentioning

confidence: 99%

Data-Driven Modeling for Precision Medicine in Pediatric Acute Liver Failure

Zamora

Vodovotz

et al. 2016

Mol Med

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“…By binding CD81, the HCVe2 protein has been shown to induce RANTES-CCL5 expression by T cells, whereas overexpressed RANTES-CCL5 binds the CCR5 receptor, which results in receptor internalization. This reduction in the levels of chemokine receptors associated with cytotoxic responses in T cells may impair the chemotaxis of these cells to the liver and allow for viral persistence [19,20]. The primary cellular defense mechanism active during HCV infection is the synthesis of antiviral cytokines such as type I interferon (IFN α/β).…”

Section: Hepatitis C Virus and Cytokine Productionmentioning

confidence: 99%

Rethinking cytokine function during hepatitis A and hepatitis C infections

Fierro¹,

Castro-García²,

Panduro³

2013

ABB

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Hepatitis A virus (HAV) and hepatitis C virus (HCV) are both viruses with hepatotropic lifestyles. HAV induces an acute infection that results in the elimination of the virus by the host whereas HCV is typically able to establish a persistent infection that may result in cirrhosis and hepatocellular carcinoma. The mechanisms responsible for this difference are unknown. However, given HAV and HCV are both non-cytophatic viruses, the observed symptoms and liver injury during the infections are the result of specific immune responses under the control of cytokines. Thus, the production of cytokines during hepatotropic viral infections may constitute a mechanism leading to different outcomes. Therefore, understanding the differences in the cytokine patterns induced in response to HAV and HCV is likely to provide important insights into the cytokine-mediated mechanisms underlying the long-term persistence of HCV, the broad spectrum of clinical manifestations induced by HAV and the resolution of HAV infection during the acute phase. Herein, we focus on discoveries that hold promise in identifying cytokines as therapeutic targets for the treatment of viral hepatitis.

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“…Thus a Th1 chemokine receptor set can be defined: CCR5 and CXCR3; while CCR3, CCR4 and CCR8 are linked to Th2 responses (Larrubia et al, 2008). Therefore, in a viral infection a certain subset of chemokines are especially interesting, as the Th1 response is considered the adequate and efficient response type.…”

Section: Chemokines In the Adaptive Immune Responsementioning

confidence: 99%