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Virulence Dec 2023Influenza viruses, including four major types (A, B, C, and D), can cause mild-to-severe and lethal diseases in humans and animals. Influenza viruses evolve rapidly... (Review)
Review
Influenza viruses, including four major types (A, B, C, and D), can cause mild-to-severe and lethal diseases in humans and animals. Influenza viruses evolve rapidly through antigenic drift (mutation) and shift (reassortment of the segmented viral genome). New variants, strains, and subtypes have emerged frequently, causing epidemic, zoonotic, and pandemic infections, despite currently available vaccines and antiviral drugs. In recent years, avian influenza viruses, such as H5 and H7 subtypes, have caused hundreds to thousands of zoonotic infections in humans with high case fatality rates. The likelihood of these animal influenza viruses acquiring airborne transmission in humans through viral evolution poses great concern for the next pandemic. Severe influenza viral disease is caused by both direct viral cytopathic effects and exacerbated host immune response against high viral loads. Studies have identified various mutations in viral genes that increase viral replication and transmission, alter tissue tropism or species specificity, and evade antivirals or pre-existing immunity. Significant progress has also been made in identifying and characterizing the host components that mediate antiviral responses, pro-viral functions, or immunopathogenesis following influenza viral infections. This review summarizes the current knowledge on viral determinants of influenza virulence and pathogenicity, protective and immunopathogenic aspects of host innate and adaptive immune responses, and antiviral and pro-viral roles of host factors and cellular signalling pathways. Understanding the molecular mechanisms of viral virulence factors and virus-host interactions is critical for the development of preventive and therapeutic measures against influenza diseases.
Topics: Humans; Animals; Influenza, Human; Virulence; Orthomyxoviridae Infections; Influenza A virus; Orthomyxoviridae; Influenza Vaccines; Antiviral Agents; Virus Replication; Influenza in Birds
PubMed: 37339323
DOI: 10.1080/21505594.2023.2223057 -
Cytokine & Growth Factor Reviews Apr 2022Many studies have been conducted over the last few decades to understand better the functions of IRF3 and IRF7 in antiviral immune responses. However, the precise... (Review)
Review
Many studies have been conducted over the last few decades to understand better the functions of IRF3 and IRF7 in antiviral immune responses. However, the precise underlying molecular mechanism of IRF1-mediated immune response remains largely unknown. Recent studies indicate that IRF1 exerts strong antiviral activities against several viral infections through diverse mechanisms, both in IFN-dependent and IFN-independent manners. Nevertheless, the efficacy and kinetics of inducing IFNs and ISGs remain unknown. Here we summarize the recent advances in IRF1 research and highlight its potential roles in initiating IFN immune responses and subsequent IRF1-triggering antiviral responses. Challenges regarding the IFN positive feedback mediated by IRF7 during infection will be discussed; this classical loop may also be mediated in part by IRF1. Therefore, we propose a revised model that may help decipher the functional roles of IRF1 in antiviral immunity.
Topics: Antiviral Agents; Humans; Immunity, Innate; Interferon Regulatory Factor-1; Signal Transduction; Virus Diseases; Virus Replication
PubMed: 35090813
DOI: 10.1016/j.cytogfr.2022.01.004 -
Viruses Apr 2021The emergence or re-emergence of viruses with epidemic and/or pandemic potential, such as Ebola, Zika, Middle East Respiratory Syndrome (MERS-CoV), Severe Acute... (Review)
Review
The emergence or re-emergence of viruses with epidemic and/or pandemic potential, such as Ebola, Zika, Middle East Respiratory Syndrome (MERS-CoV), Severe Acute Respiratory Syndrome Coronavirus 1 and 2 (SARS and SARS-CoV-2) viruses, or new strains of influenza represents significant human health threats due to the absence of available treatments. Vaccines represent a key answer to control these viruses. However, in the case of a public health emergency, vaccine development, safety, and partial efficacy concerns may hinder their prompt deployment. Thus, developing broad-spectrum antiviral molecules for a fast response is essential to face an outbreak crisis as well as for bioweapon countermeasures. So far, broad-spectrum antivirals include two main categories: the family of drugs targeting the host-cell machinery essential for virus infection and replication, and the family of drugs directly targeting viruses. Among the molecules directly targeting viruses, nucleoside analogues form an essential class of broad-spectrum antiviral drugs. In this review, we will discuss the interest for broad-spectrum antiviral strategies and their limitations, with an emphasis on virus-targeted, broad-spectrum, antiviral nucleoside analogues and their mechanisms of action.
Topics: Adenosine Monophosphate; Alanine; Amides; Animals; Antiviral Agents; Hemorrhagic Fever, Ebola; Humans; Middle East Respiratory Syndrome Coronavirus; Mutagenesis; Nucleosides; Pyrazines; Ribavirin; SARS-CoV-2; Virus Replication; Zika Virus; Zika Virus Infection; COVID-19 Drug Treatment
PubMed: 33924302
DOI: 10.3390/v13040667 -
Reviews in Medical Virology Mar 2021Azithromycin (AZM) is a synthetic macrolide antibiotic effective against a broad range of bacterial and mycobacterial infections. Due to an additional range of... (Review)
Review
Azithromycin (AZM) is a synthetic macrolide antibiotic effective against a broad range of bacterial and mycobacterial infections. Due to an additional range of anti-viral and anti-inflammatory properties, it has been given to patients with the coronaviruses SARS-CoV or MERS-CoV. It is now being investigated as a potential candidate treatment for SARS-CoV-2 having been identified as a candidate therapeutic for this virus by both in vitro and in silico drug screens. To date there are no randomised trial data on its use in any novel coronavirus infection, although a large number of trials are currently in progress. In this review, we summarise data from in vitro, murine and human clinical studies on the anti-viral and anti-inflammatory properties of macrolides, particularly AZM. AZM reduces in vitro replication of several classes of viruses including rhinovirus, influenza A, Zika virus, Ebola, enteroviruses and coronaviruses, via several mechanisms. AZM enhances expression of anti-viral pattern recognition receptors and induction of anti-viral type I and III interferon responses. Of relevance to severe coronavirus-19 disease (COVID-19), which is characterised by an over-exuberant innate inflammatory response, AZM also has anti-inflammatory properties including suppression of IL-1beta, IL-2, TNF and GM-CSF. AZM inhibits T cells by inhibiting calcineurin signalling, mammalian target of rapamycin activity and NFκB activation. AZM particularly targets granulocytes where it concentrates markedly in lysosomes, particularly affecting accumulation, adhesion, degranulation and apoptosis of neutrophils. Given its proven safety, affordability and global availability, tempered by significant concerns about antimicrobial stewardship, there is an urgent mandate to perform well-designed and conducted randomised clinical trials.
Topics: Animals; Anti-Inflammatory Agents; Antiviral Agents; Azithromycin; Humans; Virus Diseases
PubMed: 32969125
DOI: 10.1002/rmv.2163 -
Hepatology (Baltimore, Md.) Jul 2022Chronic HBV infection is a global public health burden estimated to impact nearly 300 million persons worldwide. Despite the advent of potent antiviral agents that... (Review)
Review
Chronic HBV infection is a global public health burden estimated to impact nearly 300 million persons worldwide. Despite the advent of potent antiviral agents that effectively suppress viral replication, HBV cure remains difficult to achieve because of the persistence of covalently closed circular DNA (cccDNA), HBV-DNA integration into the host genome, and impaired immune response. Indefinite treatment is necessary for most patients to maintain level of viral suppression. The success of direct-acting antivirals (DAAs) for hepatitis C treatment has rejuvenated the search for a cure for chronic hepatitis B (CHB), though an HBV cure likely requires an additional layer: immunomodulators for restoration of robust immune responses. DAAs such as entry inhibitors, capsid assembly modulators, inhibitors of subviral particle release, cccDNA silencers, and RNA interference molecules have reached clinical development. Immunomodulators, namely innate immunomodulators (Toll-like receptor agonists), therapeutic vaccines, checkpoint inhibitors, and monoclonal antibodies, are also progressing toward clinical development. The future of the HBV cure possibly lies in triple combination therapies with concerted action on replication inhibition, antigen reduction, and immune stimulation. Many obstacles remain, such as overcoming translational failures, choosing the right endpoint using the right biomarkers, and leveraging current treatments in combination regimens to enhance response rates. This review gives an overview of the current therapies for CHB, HBV biomarkers used to evaluate treatment response, and development of DAAs and immune-targeting drugs and discusses the limitations and unanswered questions on the journey to an HBV cure.
Topics: Antiviral Agents; Biomarkers; DNA, Circular; DNA, Viral; Hepatitis B virus; Hepatitis B, Chronic; Hepatitis C, Chronic; Humans; Immunologic Factors; Virus Replication
PubMed: 34990029
DOI: 10.1002/hep.32314 -
Molecules (Basel, Switzerland) Mar 2019Epstein⁻Barr virus (EBV) is a human γ-herpesvirus that infects up to 95% of the adult population. Primary EBV infection usually occurs during childhood and is... (Review)
Review
Epstein⁻Barr virus (EBV) is a human γ-herpesvirus that infects up to 95% of the adult population. Primary EBV infection usually occurs during childhood and is generally asymptomatic, though the virus can cause infectious mononucleosis in 35⁻50% of the cases when infection occurs later in life. EBV infects mainly B-cells and epithelial cells, establishing latency in resting memory B-cells and possibly also in epithelial cells. EBV is recognized as an oncogenic virus but in immunocompetent hosts, EBV reactivation is controlled by the immune response preventing transformation in vivo. Under immunosuppression, regardless of the cause, the immune system can lose control of EBV replication, which may result in the appearance of neoplasms. The primary malignancies related to EBV are B-cell lymphomas and nasopharyngeal carcinoma, which reflects the primary cell targets of viral infection in vivo. Although a number of antivirals were proven to inhibit EBV replication in vitro, they had limited success in the clinic and to date no antiviral drug has been approved for the treatment of EBV infections. We review here the antiviral drugs that have been evaluated in the clinic to treat EBV infections and discuss novel molecules with anti-EBV activity under investigation as well as new strategies to treat EBV-related diseases.
Topics: Animals; Antiviral Agents; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; Lymphoma, B-Cell; Virus Replication
PubMed: 30871092
DOI: 10.3390/molecules24050997 -
Antiviral Research Feb 2023Effective antivirals provide crucial benefits during the early phase of an influenza pandemic, when vaccines are still being developed and manufactured. Currently, two... (Review)
Review
Effective antivirals provide crucial benefits during the early phase of an influenza pandemic, when vaccines are still being developed and manufactured. Currently, two classes of viral protein-targeting drugs, neuraminidase inhibitors and polymerase inhibitors, are approved for influenza treatment and post-exposure prophylaxis. Resistance to both classes has been documented, highlighting the need to develop novel antiviral options that may include both viral and host-targeted inhibitors. Such efforts will form the basis of management of seasonal influenza infections and of strategic planning for future influenza pandemics. This review focuses on the two classes of approved antivirals, their drawbacks, and ongoing work to characterize novel agents or combination therapy approaches to address these shortcomings. The importance of these topics in the ongoing process of influenza pandemic planning is also discussed.
Topics: Humans; Antiviral Agents; Drug Resistance, Viral; Enzyme Inhibitors; Influenza, Human; Neuraminidase; Oseltamivir; Pandemics
PubMed: 36567025
DOI: 10.1016/j.antiviral.2022.105499 -
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 -
Current Rheumatology Reports Nov 2019Cryoglobulins are immunoglobulins with the ability to precipitate at temperatures <37 °C. They are related to hematological disorders, infections [especially hepatitis... (Review)
Review
PURPOSE OF THE REVIEW
Cryoglobulins are immunoglobulins with the ability to precipitate at temperatures <37 °C. They are related to hematological disorders, infections [especially hepatitis C virus (HCV)], and autoimmune diseases. In this article, the state of the art on Cryoglobulinemic Vasculitis (CV), in a helpful and schematic way, with a special focus on HCV related Mixed Cryoglobulinemia treatment are reviewed.
RECENT FINDINGS
Direct - acting antivirals (DAA) against HCV have emerged as an important key in HCV treatment to related Cryoglobulinemic Vasculitis, and should be kept in mind as the initial treatment in non-severe manifestations. On the other hand, a recent consensus panel has published their recommendations for treatment in severe and life threatening manifestations of Mixed Cryoglobulinemias. HCV-Cryoglobulinemic vasculitis is the most frequent form of CV. There are new treatment options in HCV-CV with DAA, with an important number of patients achieving complete response and sustained virologic response (SVR). In cases of severe forms of CV, treatment with Rituximab and PLEX are options. The lack of data on maintenance therapy could impulse future studies in this setting.
Topics: Antiviral Agents; Cryoglobulinemia; Humans; Treatment Outcome; Vasculitis
PubMed: 31741077
DOI: 10.1007/s11926-019-0859-0 -
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