Dataset Information

CD127 expression, exhaustion status and antigen specific proliferation predict sustained virologic response to IFN in HCV/HIV co-infected individuals.

ABSTRACT: Hepatitis C virus (HCV) infection is a major cause of morbidity and mortality in the HIV co-infected population. Interferon-alpha (IFN-?) remains a major component of anti-HCV therapy despite its deleterious effects on the immune system. Furthermore, IFN-? was recently shown to diminish the size of the latent HIV reservoir. The objectives of this study were to monitor the impact of IFN-? on T cell phenotype and proliferation of HIV and HCV-specific T cells during IFN therapy, and to identify immune markers that can predict the response to IFN in HICV/HIV co-infected patients. We performed longitudinal analyses of T cell numbers, phenotype and function in co-infected patients undergoing IFN-? therapy with different outcomes including IFN-? non-responders (NR) (n?=?9) and patients who achieved sustained virologic response (SVR) (n?=?19). We examined the expression of activation (CD38, HLA-DR), functional (CD127) and exhaustion markers (PD1, Tim-3, CD160 and CD244) on total CD4 and CD8 T cells before, during and after therapy. In addition, we examined the HIV- and HCV-specific proliferative responses against HIV-p24 and HCV-NS3 proteins. Frequencies of CD127+ CD4 T cells were higher in SVR than in NR patients at baseline. An increase in CD127 expression on CD8 T cells was observed after IFN-? therapy in all patients. In addition, CD8 T cells from NR patients expressed a higher exhaustion status at baseline. Finally, SVR patients exhibited higher proliferative response against both HIV and HCV antigens at baseline. Altogether, SVR correlated with higher expression of CD127, lower T cell exhaustion status and better HIV and HCV proliferative responses at baseline. Such factors might be used as non-invasive methods to predict the success of IFN-based therapies in co-infected individuals.

SUBMITTER: Kared H

PROVIDER: S-EPMC4090061 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

CD127 expression, exhaustion status and antigen specific proliferation predict sustained virologic response to IFN in HCV/HIV co-infected individuals.

Kared Hassen H Saeed Sahar S Klein Marina B MB Shoukry Naglaa H NH

PloS one 20140709 7

Hepatitis C virus (HCV) infection is a major cause of morbidity and mortality in the HIV co-infected population. Interferon-alpha (IFN-α) remains a major component of anti-HCV therapy despite its deleterious effects on the immune system. Furthermore, IFN-α was recently shown to diminish the size of the latent HIV reservoir. The objectives of this study were to monitor the impact of IFN-α on T cell phenotype and proliferation of HIV and HCV-specific T cells during IFN therapy, and to identify imm ...[more]

PMID: 25007250

Similar Datasets

Project description:Background & aimsChronic hepatitis C virus (HCV) infection is an important risk factor for hepatocellular carcinoma (HCC). Despite effective antiviral therapies, the risk for HCC is decreased but not eliminated after a sustained virologic response (SVR) to direct-acting antiviral (DAA) agents, and the risk is higher in patients with advanced fibrosis. We investigated HCV-induced epigenetic alterations that might affect risk for HCC after DAA treatment in patients and mice with humanized livers.MethodsWe performed genome-wide ChIPmentation-based ChIP-Seq and RNA-seq analyses of liver tissues from 6 patients without HCV infection (controls), 18 patients with chronic HCV infection, 8 patients with chronic HCV infection cured by DAA treatment, 13 patients with chronic HCV infection cured by interferon therapy, 4 patients with chronic hepatitis B virus infection, and 7 patients with nonalcoholic steatohepatitis in Europe and Japan. HCV-induced epigenetic modifications were mapped by comparative analyses with modifications associated with other liver disease etiologies. uPA/SCID mice were engrafted with human hepatocytes to create mice with humanized livers and given injections of HCV-infected serum samples from patients; mice were given DAAs to eradicate the virus. Pathways associated with HCC risk were identified by integrative pathway analyses and validated in analyses of paired HCC tissues from 8 patients with an SVR to DAA treatment of HCV infection.ResultsWe found chronic HCV infection to induce specific genome-wide changes in H3K27ac, which correlated with changes in expression of mRNAs and proteins. These changes persisted after an SVR to DAAs or interferon-based therapies. Integrative pathway analyses of liver tissues from patients and mice with humanized livers demonstrated that HCV-induced epigenetic alterations were associated with liver cancer risk. Computational analyses associated increased expression of SPHK1 with HCC risk. We validated these findings in an independent cohort of patients with HCV-related cirrhosis (n = 216), a subset of which (n = 21) achieved viral clearance.ConclusionsIn an analysis of liver tissues from patients with and without an SVR to DAA therapy, we identified epigenetic and gene expression alterations associated with risk for HCC. These alterations might be targeted to prevent liver cancer in patients treated for HCV infection.

Project description:BackgroundThe measurement of hepatitis C virus core antigen (HCV-coreAg) has been shown to be an indicator of active HCV infection. The aim of the present study was 1) to investigate the stability and effectiveness of HCV-coreAg and HCV-RNA quantification in HCV infection with or without HIV-1 coinfection, 2) to explore the association between the HCV-coreAg/HCV-RNA (Ag/RNA) ratio and the immune status in chronic HCV/HIV-1-coinfected patients.MethodsA longitudinal investigation comprised of 227 HCV-monoinfected (n = 129) and HCV/HIV-1-coinfected (n = 98) patients was initiated in August 2009, and 139 (73 with HCV monoinfection and 66 with HCV/HIV-1 coinfection) were followed up in August 2012. Both HCV core antigen and HCV RNA quantification were determined on this cryopreserved plasma. HCV core antigen and HCV RNA quantification were performed subsequently. In addition, an in vitro experiment investigating the possibility of degradation of HCV components (core antigen and RNA) were conducted.ResultsSignificant and stable correlations (p < 0.001) were observed both in chronic HCV-monoinfected and HCV/HIV-1-coinfected patients over the 3-year observation. Coinfected patients with immunocompromised condition had a significantly higher (p < 0.05) Ag/RNA ratios than those patients with immunocompetent condition both at two time points (2009 and 2012). Moreover, the Ag/RNA ratios were negatively correlated with CD4+ T-cell counts (p < 0.001). An in vitro experiment investigated the possibility of the slower degradation of HCV particles under HIV-related immunocompromised condition was conducted and the data demonstrated that the Ag/RNA ratios were significantly higher in HIV-1-positive plasma than in healthy plasma (p = 0.005) in this study.ConclusionsOur longitudinal study indicated that the HCV-coreAg presented comparable dynamics over time as HCV RNA in chronic HCV-infected patients. Meanwhile, the HCV-coreAg/HCV-RNA ratio was closely associated with immune status in HCV/HIV-1-coinfected patients.

Dataset Information

CD127 expression, exhaustion status and antigen specific proliferation predict sustained virologic response to IFN in HCV/HIV co-infected individuals.

Publications

CD127 expression, exhaustion status and antigen specific proliferation predict sustained virologic response to IFN in HCV/HIV co-infected individuals.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure