scholarly journals Chronic HCV Infection Is Associated with Overexpression of Human Endogenous Retroviruses that Persists after Drug-Induced Viral Clearance

2020 ◽  
Vol 21 (11) ◽  
pp. 3980
Author(s):  
Pier-Angelo Tovo ◽  
Silvia Garazzino ◽  
Valentina Daprà ◽  
Carla Alliaudi ◽  
Erika Silvestro ◽  
...  
Keyword(s):  
Viral Infections ◽  
White Blood Cells ◽  
Autoimmune Disorders ◽  
Viral Clearance ◽  
Hcv Infection ◽  
Endogenous Retroviruses ◽  
Drug Induced ◽  
Human Endogenous Retroviruses ◽  
Chronic Hcv Infection ◽  
Chronic Hcv

Chronic hepatitis C virus (HCV) infection is associated with several hepatic and extrahepatic complications, including cancers and autoimmune disorders, whose frequency is reduced but not abolished after drug-induced viral clearance. The causes of these complications and of their persistence are ill-defined. Human endogenous retroviruses (HERVs) are remnants of ancestral infections and constitute 8% of the human genome. Most HERV elements are inactive, but some are transcribed. HERV overexpression is associated with many cancers and autoimmune diseases with a putative pathogenetic role. Several viral infections trigger HERV activation, but there are no studies on HCV-infected subjects. We assessed, through a PCR real-time amplification assay, the transcription levels of the pol genes of HERV-H, -K, and -W, and of their repressor TRIM28 in white blood cells (WBCs) of vertically infected children, both before and after therapy with direct-acting antivirals (DAAs). The results documented significantly higher expressions of HERV-H-pol and HERV-K-pol, not of HERV-W-pol, in HCV-infected subjects as compared to age-matched controls. HERV RNA levels remained unchanged after DAA-driven viral clearance. No significant variations in transcription levels of TRIM28 were observed in infected subjects. Our findings demonstrate HERV-H-pol and HERV-K-pol overexpression in subjects with chronic HCV infection, without variations after a positive response to DAAs; this might justify their predisposition to cancers and autoimmune disorders that persist after a DAA-induced resolution of viremia.

scholarly journals Reversal of T Cell Exhaustion in Chronic HCV Infection

Viruses ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 799
Author(s):  
Sylwia Osuch ◽  
Karin J. Metzner ◽  
Kamila Caraballo Cortés
Keyword(s):  
T Cell ◽  
Antiviral Treatment ◽  
Immune Dysfunction ◽  
T Cell Response ◽  
Viral Clearance ◽  
Hcv Infection ◽  
Chronic Hcv Infection ◽  
Long Term Consequences ◽  
Chronic Hcv

The long-term consequences of T cell responses’ impairment in chronic HCV infection are not entirely characterized, although they may be essential in the context of the clinical course of infection, re-infection, treatment-mediated viral clearance and vaccine design. Furthermore, it is unclear whether a complete reinvigoration of HCV-specific T cell response may be feasible. In most studies, attempting to reverse the effects of compromised immune response quality by specific blockades of negative immune regulators, a restoration of functional competence of HCV-specific T cells was shown. This implies that HCV-induced immune dysfunction may be reversible. The advent of highly successful, direct-acting antiviral treatment (DAA) for chronic HCV infection instigated investigation whether the treatment-driven elimination of viral antigens restores T cell function. Most of studies demonstrated that DAA treatment may result in at least partial restoration of T cell immune function. They also suggest that a complete restoration comparable to that seen after spontaneous viral clearance may not be attained, pointing out that long-term antigenic stimulation imprints an irreversible change on the T cell compartment. Understanding the mechanisms of HCV-induced immune dysfunction and barriers to immune restoration following viral clearance is of utmost importance to diminish the possible long-term consequences of chronic HCV infection.

Spontaneous viral clearance of chronic HCV infection in Upper Egypt: A community-based study with a 10year follow-up

2010 ◽  
Vol 11 (4) ◽  
pp. 197-201 ◽  
Author(s):  
Madiha Mohamed El-Attar ◽  
Mohamed Abdel-Hamid Ahmed ◽  
Magda Shehata Hasan ◽  
Mohamed Ahmed Aly ◽  
Ahmed Medhat Nasr
Keyword(s):  
Viral Clearance ◽  
Hcv Infection ◽  
Community Based ◽  
Upper Egypt ◽  
Spontaneous Viral Clearance ◽  
Chronic Hcv Infection ◽  
Chronic Hcv

Rapid viral clearance with IFN-α 2b induction therapy and ribavirinfor chronic HCV infection

2000 ◽  
Vol 32 ◽  
pp. 38 ◽  
Author(s):  
K. Bjøro ◽  
H. Bell ◽  
K.B. Hellum ◽  
B. Myrvang ◽  
K. Skaug
Keyword(s):  
Induction Therapy ◽  
Viral Clearance ◽  
Hcv Infection ◽  
Chronic Hcv Infection ◽  
Chronic Hcv

Chronic hepatitis C virus infection: An internist’s opinion (Part 1)

2016 ◽  
Vol 88 (10) ◽  
pp. 105-113
Author(s):  
M L Zubkin ◽  
V I Chervinko ◽  
Yu V Ovchinnikov ◽  
E V Kryukov ◽  
O N Kotenko
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Kidney Injury ◽  
Mixed Cryoglobulinemia ◽  
Autoimmune Disorders ◽  
Hcv Infection ◽  
Inflammatory Processes ◽  
Chronic Hcv Infection ◽  
Chronic Hcv

Hepatitis C virus (HCV) infection results in not only chronic hepatitis and subsequent complications as liver cirrhosis and hepatocellular carcinoma, but also in a significant number of other diseases, the so-called extrahepatic manifestations of chronic HCV infection. This is because of viral hepatotropicity and lymphotropicity. The most striking example of the course of chronic HCV infection, in which the infectious and inflammatory processes are concurrent with autoimmune disorders and carcinogenesis, is mixed cryoglobulinemia and B-cell non-Hodgkin’s lymphoma. The pathogenesis of these diseases is based on the clonal expansion of B cells, which occurs under their prolonged stimulation with the virus or viral proteins. Part 1 of this review is devoted to the analysis of a correlation of chronic HCV infection with lymphoproliferative and autoimmune disorders, as well as its association with kidney injury.

scholarly journals Liver-Infiltrating Lymphocytes in Chronic Human Hepatitis C Virus Infection Display an Exhausted Phenotype with High Levels of PD-1 and Low Levels of CD127 Expression

2006 ◽  
Vol 81 (6) ◽  
pp. 2545-2553 ◽  
Author(s):  
Henry Radziewicz ◽  
Chris C. Ibegbu ◽  
Marina L. Fernandez ◽  
Kimberly A. Workowski ◽  
Kamil Obideen ◽  
...  
Keyword(s):  
T Cells ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Cell ◽  
Viral Infections ◽  
T Cell Response ◽  
Hcv Infection ◽  
Interleukin 7 ◽  
Chronic Hcv Infection ◽  
Chronic Hcv

ABSTRACT The majority of people infected with hepatitis C virus (HCV) fail to generate or maintain a T-cell response effective for viral clearance. Evidence from murine chronic viral infections shows that expression of the coinhibitory molecule PD-1 predicts CD8+ antiviral T-cell exhaustion and may contribute to inadequate pathogen control. To investigate whether human CD8+ T cells express PD-1 and demonstrate a dysfunctional phenotype during chronic HCV infection, peripheral and intrahepatic HCV-specific CD8+ T cells were examined. We found that in chronic HCV infection, peripheral HCV-specific T cells express high levels of PD-1 and that blockade of the PD-1/PD-L1 interaction led to an enhanced proliferative capacity. Importantly, intrahepatic HCV-specific T cells, in contrast to those in the periphery, express not only high levels of PD-1 but also decreased interleukin-7 receptor alpha (CD127), an exhausted phenotype that was HCV antigen specific and compartmentalized to the liver, the site of viral replication.

Treatment of acute hepatitis C infection with interferon-alfa 2b monotherapy prevents development of chronic HCV infection

2001 ◽  
Vol 120 (5) ◽  
pp. A567-A567 ◽  
Author(s):  
E JAECKEL ◽  
M CORNBERG ◽  
T SANTANTONIO ◽  
J MAYER ◽  
H WEDEMEYER ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Acute Hepatitis ◽  
Interferon Alfa ◽  
Hcv Infection ◽  
Acute Hepatitis C ◽  
Hepatitis C Infection ◽  
Chronic Hcv Infection ◽  
Chronic Hcv
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