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World Journal of Gastroenterology Nov 2014Hepatitis C virus (HCV) infection represents an important public health problem worldwide. Reduction of HCV morbidity and mortality is a current challenge owned to... (Review)
Review
Hepatitis C virus (HCV) infection represents an important public health problem worldwide. Reduction of HCV morbidity and mortality is a current challenge owned to several viral and host factors. Virus molecular evolution plays an important role in HCV transmission, disease progression and therapy outcome. The high degree of genetic heterogeneity characteristic of HCV is a key element for the rapid adaptation of the intrahost viral population to different selection pressures (e.g., host immune responses and antiviral therapy). HCV molecular evolution is shaped by different mechanisms including a high mutation rate, genetic bottlenecks, genetic drift, recombination, temporal variations and compartmentalization. These evolutionary processes constantly rearrange the composition of the HCV intrahost population in a staging manner. Remarkable advances in the understanding of the molecular mechanism controlling HCV replication have facilitated the development of a plethora of direct-acting antiviral agents against HCV. As a result, superior sustained viral responses have been attained. The rapidly evolving field of anti-HCV therapy is expected to broad its landscape even further with newer, more potent antivirals, bringing us one step closer to the interferon-free era.
Topics: Animals; Antiviral Agents; Disease Progression; Drug Resistance, Viral; Drug Therapy, Combination; Evolution, Molecular; Genotype; Hepacivirus; Hepatitis C; Host-Pathogen Interactions; Humans; Phenotype; Treatment Outcome
PubMed: 25473152
DOI: 10.3748/wjg.v20.i43.15992 -
IUBMB Life Apr 2022Targeting intracellular components for lysosomal degradation by autophagy not only maintains cellular homeostasis but also counteracts the effects of external stimuli,... (Review)
Review
Targeting intracellular components for lysosomal degradation by autophagy not only maintains cellular homeostasis but also counteracts the effects of external stimuli, including invading pathogens. Among various kinds of pathogens, viruses have been extensively shown to induce autophagy to benefit viral growth in infected cells and to modulate host defense responses, such as innate antiviral immunity. Recently, numerous lines of evidence have implied that virus-induced autophagy triggers multilayer mechanisms to regulate the innate antiviral response of host cells, thus promoting a balance in virus-host cell interactions. In this review, the detailed mechanisms underlying autophagy and the innate antiviral immune response are first described. Then, I summarize the current information regarding the diverse functional role(s) of autophagy in the control of antiviral defenses against different types of viral infections. Moreover, the physiological significance of autophagy-regulated antiviral responses on the viral life cycle and the potential autophagy alterations induced by virus-associated antiviral signaling is further discussed.
Topics: Antiviral Agents; Autophagy; Host-Pathogen Interactions; Humans; Immunity, Innate; Virus Diseases; Viruses
PubMed: 34859938
DOI: 10.1002/iub.2582 -
Journal of Hepatology Dec 2021Patients with HCV who achieve a sustained virological response (SVR) on direct-acting antiviral (DAA) therapy still need to be monitored for signs of liver disease...
BACKGROUND & AIMS
Patients with HCV who achieve a sustained virological response (SVR) on direct-acting antiviral (DAA) therapy still need to be monitored for signs of liver disease progression. To this end, the identification of both disease biomarkers and therapeutic targets is necessary.
METHODS
Extracellular vesicles (EVs) purified from plasma of 15 healthy donors (HDs), and 16 HCV-infected patients before (T0) and after (T6) DAA treatment were utilized for functional and miRNA cargo analysis. EVs purified from plasma of 17 HDs and 23 HCV-infected patients (T0 and T6) were employed for proteomic and western blot analyses. Functional analysis in LX2 cells measured fibrotic markers (mRNAs and proteins) in response to EVs. Structural analysis was performed by qPCR, label-free liquid chromatography-mass spectrometry and western blot.
RESULTS
On the basis of observations indicating functional differences (i.e. modulation of FN-1, ACTA2, Smad2/3 phosphorylation, collagen deposition) of plasma-derived EVs from HDs, T0 and T6, we performed structural analysis of EVs. We found consistent differences in terms of both miRNA and protein cargos: (i) antifibrogenic miR204-5p, miR181a-5p, miR143-3p, miR93-5p and miR122-5p were statistically underrepresented in T0 EVs compared to HD EVs, while miR204-5p and miR143-3p were statistically underrepresented in T6 EVs compared to HD EVs (p <0.05); (ii) proteomic analysis highlighted, in both T0 and T6, the modulation of several proteins with respect to HDs; among them, the fibrogenic protein DIAPH1 was upregulated (Log fold change of 4.4).
CONCLUSIONS
Taken together, these results highlight structural EV modifications that are conceivably causal for long-term liver disease progression in patients with HCV despite DAA-mediated SVR.
LAY SUMMARY
Direct-acting antivirals lead to virological cure in the majority of patients with chronic hepatitis C virus infection. However, the risk of liver disease progression or complications in patients with fibrosis and cirrhosis remains in some patients even after virological cure. Herein, we show that extracellular vesicle modifications could be linked to long-term liver disease progression in patients who have achieved virological cure; these modifications could potentially be used as biomarkers or treatment targets in such patients.
Topics: Antiviral Agents; Cell Communication; Hepacivirus; Hepatitis C; Humans; Mass Spectrometry; Sustained Virologic Response
PubMed: 34271004
DOI: 10.1016/j.jhep.2021.07.003 -
Antiviral Chemistry & Chemotherapy 2018
Topics: Antiviral Agents; Dose-Response Relationship, Drug; Humans; Microbial Sensitivity Tests; Molecular Structure; Nucleosides; Prodrugs; Structure-Activity Relationship; Viruses
PubMed: 29890841
DOI: 10.1177/2040206618781410 -
Current Opinion in Virology Feb 2022To establish successful infection in cells, it is essential for hepatitis C virus (HCV) to overcome intracellular antiviral responses. The host cell mechanism that... (Review)
Review
To establish successful infection in cells, it is essential for hepatitis C virus (HCV) to overcome intracellular antiviral responses. The host cell mechanism that fights against the virus culminates in the production of interferons (IFNs), IFN-stimulated genes (ISGs) and pro-inflammatory cytokines as well as the induction of autophagy and apoptosis. HCV has developed multiple means to disrupt the host signaling pathways that lead to these antiviral responses. HCV impedes signaling pathways initiated by pattern-recognition receptors (PRRs), usurps and uses the antiviral autophagic response to enhance its replication, alters mitochondrial dynamics and metabolism to prevent cell death and attenuate IFN response, and dysregulates inflammasomal response to cause IFN resistance and immune tolerance. These effects of HCV allow HCV to successful replicate and persist in its host cells.
Topics: Antiviral Agents; Hepacivirus; Hepatitis C; Humans; Immunity, Innate; Interferons; Virus Replication
PubMed: 34973476
DOI: 10.1016/j.coviro.2021.12.010 -
Deutsches Arzteblatt International Jan 2017Among patients with chronic hepatitis C, 20-30% develop hepatic cirrhosis and its complications within 30 years. The antiviral treatment of hepatitis C, previously... (Review)
Review
BACKGROUND
Among patients with chronic hepatitis C, 20-30% develop hepatic cirrhosis and its complications within 30 years. The antiviral treatment of hepatitis C, previously interferon-based, has recently become inter - feron-free, with resulting improvements in sustained virological response rates, safety, and tolerability and a shorter duration of treatment.
METHODS
This review is based on relevant publications retrieved by a selective literature search, and particularly on studies and reviews concerning the course and treatment of hepatitis C.
RESULTS
The available drugs for interferon-free antiviral treatment of hepatitis C include inhibitors of the RNAdependent RNA polymerase, NS3/4A protease, and NS5A protein of the hepatitis C virus (HCV), and ribavirin. Typically, two specific inhibitors are given in combination; the usual duration of treatment is 12 weeks.The antiviral drugs differ in their genotypic antiviral effectiveness and resistance barriers. The appropriate drug(s) should be chosen in consideration of the patient's hepatic and renal function and potential drug interactions. These drugs are safe and well-tolerated and result in sustained virological response rates between 90% and 100%.
CONCLUSION
All patients with hepatitis C, whatever their disease stage, can derive a sustained eradication of HCV from a combination of drugs with direct antiviral activity. Viral eradication is associated with a better quality of life and with lower morbidity and mortality.
Topics: Antiviral Agents; Evidence-Based Medicine; Hepatitis C; Humans; Treatment Outcome
PubMed: 28143635
DOI: 10.3238/arztebl.2017.0011 -
Advanced Science (Weinheim,... Mar 2022SUMOylation is a ubiquitination-like post-translational modification that plays an essential role in the regulation of protein function. Recent studies have shown that... (Review)
Review
SUMOylation is a ubiquitination-like post-translational modification that plays an essential role in the regulation of protein function. Recent studies have shown that proteins from both RNA and DNA virus families can be modified by SUMO conjugation, which facilitates viral replication. Viruses can manipulate the entire process of SUMOylation through interplay with the SUMO pathway. By contrast, SUMOylation can eliminate viral infection by regulating host antiviral immune components. A deeper understanding of how SUMOylation regulates viral proteins and cellular antiviral components is necessary for the development of effective antiviral therapies. In the present review, the regulatory mechanism of SUMOylation in viral replication and infection and the antiviral immune response, and the consequences of this regulation for viral replication and engagement with antiviral innate immunity are summarized. The potential therapeutic applications of SUMOylation in diseases caused by viruses are also discussed.
Topics: Antiviral Agents; Host-Pathogen Interactions; Sumoylation; Viral Proteins; Virus Replication
PubMed: 35060688
DOI: 10.1002/advs.202104126 -
The British Journal of Nutrition Apr 2022Zn deficiency compromises its biological functions, its effect on the immune system and its antiviral activity, increasing vulnerability to infectious diseases. This... (Review)
Review
Zn deficiency compromises its biological functions, its effect on the immune system and its antiviral activity, increasing vulnerability to infectious diseases. This narrative review aims at presenting and discussing functional aspects and possible mechanisms involved in the potential role of Zn in the immune response and antiviral activity for coronavirus infectious disease-19 (COVID-19) prevention and control. The searches were conducted in PubMed and Science Direct databases, using clinical trials, experimental studies in animals and humans, case-control studies, case series, letters to the editor, and review articles published in English, without restrictions on year of publication. Search approach was based on using the terms: 'zinc', 'COVID-19', 'antiviral agents', 'immunologic factors' and 'respiratory tract infections'. Literature shows the importance of Zn as an essential mineral immunomodulator with relevant antiviral activity in the body. Thus, although there is still a scarcity of studies evaluating Zn supplementation in patients with COVID-19, the results on the topic show the necessity of controlling Zn mineral deficiency, as well as maintaining its homoeostasis in the body in order to strengthen the immune system and improve the prevention of highly complex viral infections, such as that of the COVID-19.
Topics: Antiviral Agents; Communicable Diseases; Humans; Virus Diseases; Zinc; COVID-19 Drug Treatment
PubMed: 34128459
DOI: 10.1017/S0007114521002099 -
Virus Genes Apr 2020The viruses historically implicated or currently considered as candidates for misuse in bioterrorist events are poxviruses, filoviruses, bunyaviruses, orthomyxoviruses,... (Review)
Review
The viruses historically implicated or currently considered as candidates for misuse in bioterrorist events are poxviruses, filoviruses, bunyaviruses, orthomyxoviruses, paramyxoviruses and a number of arboviruses causing encephalitis, including alpha- and flaviviruses. All these viruses are of concern for public health services when they occur in natural outbreaks or emerge in unvaccinated populations. Recent events and intelligence reports point to a growing risk of dangerous biological agents being used for nefarious purposes. Public health responses effective in natural outbreaks of infectious disease may not be sufficient to deal with the severe consequences of a deliberate release of such agents. One important aspect of countermeasures against viral biothreat agents are the antiviral treatment options available for use in post-exposure prophylaxis. These issues were adressed by the organizers of the 16th Medical Biodefense Conference, held in Munich in 2018, in a special session on the development of drugs to treat infections with viruses currently perceived as a threat to societies or associated with a potential for misuse as biothreat agents. This review will outline the state-of-the-art methods in antivirals research discussed and provide an overview of antiviral compounds in the pipeline that are already approved for use or still under development.
Topics: Antiviral Agents; Arboviruses; Bioterrorism; Filoviridae; Humans; Orthobunyavirus; Orthomyxoviridae; Paramyxovirinae; Poxviridae; Virus Diseases
PubMed: 32076918
DOI: 10.1007/s11262-020-01737-5 -
Theranostics 2023Coronavirus disease 2019 (COVID-19), an infectious disease caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global pandemic that... (Review)
Review
Coronavirus disease 2019 (COVID-19), an infectious disease caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global pandemic that has high incidence rates, spreads rapidly, and has caused more than 6.5 million deaths globally to date. Currently, several drugs have been used in the clinical treatment of COVID-19, including antivirals (e.g., molnupiravir, baricitinib, and remdesivir), monoclonal antibodies (e.g., etesevimab and tocilizumab), protease inhibitors (e.g., paxlovid), and glucocorticoids (e.g., dexamethasone). Increasing evidence suggests that circulating microRNAs (miRNAs) are important regulators of viral infection and antiviral immune responses, including the biological processes involved in regulating COVID-19 infection and subsequent complications. During viral infection, both viral genes and host cytokines regulate transcriptional and posttranscriptional steps affecting viral replication. Virus-encoded miRNAs are a component of the immune evasion repertoire and function by directly targeting immune functions. Moreover, several host circulating miRNAs can contribute to viral immune escape and play an antiviral role by not only promoting nonstructural protein (nsp) 10 expression in SARS coronavirus, but among others inhibiting NOD-like receptor pyrin domain-containing (NLRP) 3 and IL-1β transcription. Consequently, understanding the expression and mechanism of action of circulating miRNAs during SARS-CoV-2 infection will provide unexpected insights into circulating miRNA-based studies. In this review, we examined the recent progress of circulating miRNAs in the regulation of severe inflammatory response, immune dysfunction, and thrombosis caused by SARS-CoV-2 infection, discussed the mechanisms of action, and highlighted the therapeutic challenges involving miRNA and future research directions in the treatment of COVID-19.
Topics: Humans; Antiviral Agents; Circulating MicroRNA; COVID-19; MicroRNAs; SARS-CoV-2
PubMed: 36593971
DOI: 10.7150/thno.78164