scholarly journals Restoration of HCV-Specific Immune Responses with Antiviral Therapy: A Case for DAA Treatment in Acute HCV Infection

Cells ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 317 ◽  
Author(s):  
Julia L. Casey ◽  
Jordan J. Feld ◽  
Sonya A. MacParland
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Viral Infection ◽  
Antiviral Therapy ◽  
Hcv Infection ◽  
Immune Restoration ◽  
Viral Control ◽  
Acute Hcv ◽  
Ifn Treatment ◽  
Acute Hcv Infection

Worldwide, 71 million individuals are chronically infected with Hepatitis C Virus (HCV). Chronic HCV infection can lead to potentially fatal outcomes including liver cirrhosis and hepatocellular carcinoma. HCV-specific immune responses play a major role in viral control and may explain why approximately 20% of infections are spontaneously cleared before the establishment of chronicity. Chronic infection, associated with prolonged antigen exposure, leads to immune exhaustion of HCV-specific T cells. These exhausted T cells are unable to control the viral infection. Before the introduction of direct acting antivirals (DAAs), interferon (IFN)-based therapies demonstrated successful clearance of viral infection in approximately 50% of treated patients. New effective and well-tolerated DAAs lead to a sustained virological response (SVR) in more than 95% of patients regardless of viral genotype. Researchers have investigated whether treatment, and the subsequent elimination of HCV antigen, can reverse this HCV-induced exhausted phenotype. Here we review literature exploring the restoration of HCV-specific immune responses following antiviral therapy, both IFN and DAA-based regimens. IFN treatment during acute HCV infection results in greater immune restoration than IFN treatment of chronically infected patients. Immune restoration data following DAA treatment in chronically HCV infected patients shows varied results but suggests that DAA treatment may lead to partial restoration that could be improved with earlier administration. Future research should investigate immune restoration following DAA therapies administered during acute HCV infection.

scholarly journals High Level of PD-1 Expression on Hepatitis C Virus (HCV)-Specific CD8+ and CD4+ T Cells during Acute HCV Infection, Irrespective of Clinical Outcome

2011 ◽  
Vol 85 (9) ◽  
pp. 4633-4633
Author(s):  
V. Kasprowicz ◽  
J. S. zur Wiesch ◽  
T. Kuntzen ◽  
B. E. Nolan ◽  
S. Longworth ◽  
...  
Keyword(s):  
T Cells ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Clinical Outcome ◽  
Cd4 T Cells ◽  
Hcv Infection ◽  
Acute Hcv ◽  
High Level ◽  
Acute Hcv Infection

scholarly journals Impaired Hepatitis C Virus (HCV)-Specific Effector CD8+ T Cells Undergo Massive Apoptosis in the Peripheral Blood during Acute HCV Infection and in the Liver during the Chronic Phase of Infection

2008 ◽  
Vol 82 (20) ◽  
pp. 9808-9822 ◽  
Author(s):  
Henry Radziewicz ◽  
Chris C. Ibegbu ◽  
Huiming Hon ◽  
Melissa K. Osborn ◽  
Kamil Obideen ◽  
...  
Keyword(s):  
T Cells ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Cell ◽  
Chronic Phase ◽  
T Cell Response ◽  
Hcv Infection ◽  
Caspase 9 ◽  
Acute Hcv ◽  
Acute Hcv Infection

ABSTRACT A majority of patients infected with hepatitis C virus (HCV) do not sustain an effective T-cell response, and viremia persists. The mechanism leading to failure of the HCV-specific CD8+ T-cell response in patients developing chronic infection is unclear. We investigated apoptosis susceptibility of HCV-specific CD8+ T cells during the acute and chronic stages of infection. Although HCV-specific CD8+ T cells in the blood during the acute phase of infection and in the liver during the chronic phase were highly activated and expressed an effector phenotype, the majority was undergoing apoptosis. In contrast, peripheral blood HCV-specific CD8+ T cells during the chronic phase expressed a resting memory phenotype. Apoptosis susceptibility of HCV-specific CD8+ T cells was associated with very high levels of programmed death-1 (PD-1) and low CD127 expression and with significant functional T-cell deficits. Further evaluation of the “death phase” of HCV-specific CD8+ T cells during acute HCV infection showed that the majority of cells were dying by a process of cytokine withdrawal, mediated by activated caspase 9. Contraction during the acute phase occurred rapidly via this process despite the persistence of the virus. Remarkably, in the chronic phase of HCV infection, at the site of infection in the liver, a substantial frequency of caspase 9-mediated T-cell death was also present. This study highlights the importance of cytokine deprivation-mediated apoptosis with consequent down-modulation of the immune response to HCV during acute and chronic infections.

scholarly journals Detection of host immune responses in acute phase sera of spontaneous resolution versus persistent hepatitis C virus infection

2012 ◽  
Vol 93 (8) ◽  
pp. 1673-1679 ◽  
Author(s):  
Suganya Selvarajah ◽  
Sheila Keating ◽  
John Heitman ◽  
Kai Lu ◽  
Graham Simmons ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Immune Responses ◽  
Serum Levels ◽  
Hcv Infection ◽  
Serum Samples ◽  
Necrosis Factor Alpha ◽  
Acute Hcv ◽  
Chronic Hcv ◽  
Acute Hcv Infection

Prior to the identification of hepatitis C virus (HCV), transfusion-transmission was common. Viral transmission in subjects with a known date of infection allows the study of the immune responses to acute HCV infection. We analysed 39 soluble immune factors in serum samples from subjects with transfusion-transmitted HCV. Dynamic expression kinetics of interferon gamma-induced protein 10 (IP-10), tumour necrosis factor-alpha and interleukin (IL)-10 were observed during acute HCV infection. Serum IP-10 was the only analyte that was significantly elevated in HCV resolvers compared with uninfected controls. In individuals who progressed to chronic HCV elevated levels of IP-10 and IL-10 coincided with first significant alanine aminotransferase elevation and remained elevated during the first year of acute HCV infection. In addition to monitoring lack of reduction in viral load, serum levels of IP-10 and IL-10 expression during acute HCV infection may be useful biomarkers to predict the progress to chronic HCV.

scholarly journals Management of acute HCV infection in the era of direct-acting antiviral therapy

2018 ◽  
Vol 15 (7) ◽  
pp. 412-424 ◽  
Author(s):  
Marianne Martinello ◽  
Behzad Hajarizadeh ◽  
Jason Grebely ◽  
Gregory J. Dore ◽  
Gail V. Matthews
Keyword(s):  
Antiviral Therapy ◽  
Hcv Infection ◽  
Direct Acting Antiviral ◽  
Acute Hcv ◽  
Direct Acting ◽  
Acute Hcv Infection

scholarly journals The Frequency of CD127+ Hepatitis C Virus (HCV)-Specific T Cells but Not the Expression of Exhaustion Markers Predicts the Outcome of Acute HCV Infection

2013 ◽  
Vol 87 (8) ◽  
pp. 4772-4777 ◽  
Author(s):  
E.-C. Shin ◽  
S.-H. Park ◽  
M. Nascimbeni ◽  
M. Major ◽  
L. Caggiari ◽  
...  
Keyword(s):  
T Cells ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Hcv Infection ◽  
Acute Hcv ◽  
Acute Hcv Infection

scholarly journals Early Interferon Therapy for Hepatitis C Virus Infection Rescues Polyfunctional, Long-Lived CD8+ Memory T Cells

2008 ◽  
Vol 82 (20) ◽  
pp. 10017-10031 ◽  
Author(s):  
Gamal Badr ◽  
Nathalie Bédard ◽  
Mohamed S. Abdel-Hakeem ◽  
Lydie Trautmann ◽  
Bernard Willems ◽  
...  
Keyword(s):  
T Cells ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Therapeutic Intervention ◽  
Memory T Cells ◽  
Hcv Infection ◽  
Effector Memory ◽  
Acute Hepatitis C ◽  
Acute Hcv ◽  
Acute Hcv Infection

ABSTRACT The majority of acute hepatitis C virus (HCV) infections progress to chronicity and progressive liver damage. Alpha interferon (IFN-α) antiviral therapy achieves the highest rate of success when IFN-α is administered early during the acute phase, but the underlying mechanisms are unknown. We used a panel of major histocompatibility complex class I tetramers to monitor the phenotypic and functional signatures of HCV-specific T cells during acute HCV infection with different infection outcomes and during early IFN therapy. We demonstrate that spontaneous resolution correlates with the early development of polyfunctional (IFN-γ- and IL-2-producing and CD107a+) virus-specific CD8+ T cells. These polyfunctional T cells are distinguished by the expression of CD127 and Bcl-2 and represent a transitional memory T-cell subset that exhibits the phenotypic and functional signatures of both central and effector memory T cells. In contrast, HCV-specific CD8+ T cells in acute infections evolving to chronicity expressed low levels of CD127 and Bcl-2, exhibited diminished proliferation and cytokine production, and eventually disappeared from the periphery. Early therapeutic intervention with pegylated IFN-α rescued polyfunctional memory T cells expressing high levels of CD127 and Bcl-2. These cells were detectable for up to 1 year following discontinuation of therapy. Our results suggest that the polyfunctionality of HCV-specific T cells can be predictive of the outcome of acute HCV infection and that early therapeutic intervention can reconstitute the pool of long-lived polyfunctional memory T cells.

Influence of specific CD4+ T cells and antibodies on evolution of hypervariable region 1 during acute HCV infection

2008 ◽  
Vol 48 (2) ◽  
pp. 216-228 ◽  
Author(s):  
Cristiano Scottà ◽  
Anna Rosa Garbuglia ◽  
Lionello Ruggeri ◽  
Enea Spada ◽  
Luca Laurenti ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Hypervariable Region ◽  
Hcv Infection ◽  
Hypervariable Region 1 ◽  
Acute Hcv ◽  
Acute Hcv Infection

scholarly journals Analysis of Successful Immune Responses in Persons Infected with Hepatitis C Virus

2000 ◽  
Vol 191 (9) ◽  
pp. 1499-1512 ◽  
Author(s):  
Franziska Lechner ◽  
David K.H. Wong ◽  
P. Rod Dunbar ◽  
Roger Chapman ◽  
Raymond T. Chung ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Acute Infection ◽  
Hcv Infection ◽  
Ctl Response ◽  
Acute Hcv ◽  
Ifn Γ ◽  
Acute Hcv Infection

Although hepatitis C virus (HCV) infection is very common, identification of patients during acute infection is rare. Consequently, little is known about the immune response during this critical stage of the disease. We analyzed the T lymphocyte response during and after acute resolving HCV infection in three persons, using interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) and human histocompatibility leukocyte antigen (HLA) peptide tetramer assays. Acute infection was associated with a broadly directed T helper and cytotoxic T lymphocyte (CTL) response, which persisted after resolution of clinical hepatitis and clearance of viremia. At the earliest time point studied, highly activated CTL populations were observed that temporarily failed to secrete IFN-γ, a “stunned” phenotype, from which they recovered as viremia declined. In long-term HCV-seropositive persons, CTL responses were more common in persons who had cleared viremia compared with those with persistent viremia, although the frequencies of HCV-specific CTLs were lower than those found in persons during and after resolution of acute HCV infection. These studies demonstrate a strong and persistent CTL response in resolving acute HCV infection, and provide rationale to explore immune augmentation as a therapeutic intervention in chronic HCV infection.

799 KINETICS OF HEPATIC AND CIRCULATING MICRORNA-122 DURING EXPERIMENTAL ACUTE HCV INFECTION

2011 ◽  
Vol 54 ◽  
pp. S320-S321
Author(s):  
K. Krawczynski ◽  
Y. Choi ◽  
M. Odenthal ◽  
M. Ruhrlander ◽  
M. Muller ◽  
...  
Keyword(s):  
Hcv Infection ◽  
Circulating Microrna ◽  
Acute Hcv ◽  
Kinetics Of ◽  
Acute Hcv Infection
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