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Human Vaccines & Immunotherapeutics Jul 2018Genital warts are one of the most common sexually transmitted diseases worldwide. The disease is a result of infection with low-risk types of human papillomaviruses,... (Review)
Review
Genital warts are one of the most common sexually transmitted diseases worldwide. The disease is a result of infection with low-risk types of human papillomaviruses, mostly type 6 and 11. Current therapies for genital warts are mainly ablative, or alternatively topical application of imiquimod cream and sinecatechin (polyphenon E) ointment to the warts. However, low patient compliance and high recurrence rate are significant problems for the treatment of genital warts by imiquimod and ablative therapies. We summarise recent literature in this area and propose combining imiquimod with other therapies to increase the efficacy of imiquimod.
Topics: Administration, Topical; Anus Diseases; Catechin; Condylomata Acuminata; Drug Therapy, Combination; Humans; Imiquimod; Interferon Inducers; Interleukin-10; Papillomaviridae; Recurrence; Treatment Outcome
PubMed: 29505317
DOI: 10.1080/21645515.2018.1445947 -
Proceedings of the National Academy of... Mar 2020Type III IFN lambdas (IFN-λ) have recently been described as important mediators of immune responses at barrier surfaces. However, their role in autoimmune diseases...
Type III IFN lambdas (IFN-λ) have recently been described as important mediators of immune responses at barrier surfaces. However, their role in autoimmune diseases such as systemic lupus erythematosus (SLE), a condition characterized by aberrant type I IFN signaling, has not been determined. Here, we identify a nonredundant role for IFN-λ in immune dysregulation and tissue inflammation in a model of TLR7-induced lupus. IFN-λ protein is increased in murine lupus and IFN-λ receptor (Ifnlr1) deficiency significantly reduces immune cell activation and associated organ damage in the skin and kidneys without effects on autoantibody production. Single-cell RNA sequencing in mouse spleen and human peripheral blood revealed that only mouse neutrophils and human B cells are directly responsive to this cytokine. Rather, IFN-λ activates keratinocytes and mesangial cells to produce chemokines that induce immune cell recruitment and promote tissue inflammation. These data provide insights into the immunobiology of SLE and identify type III IFNs as important factors for tissue-specific pathology in this disease.
Topics: Animals; B-Lymphocytes; Cell Line; Gene Deletion; Humans; Imiquimod; Inflammation; Interferon Inducers; Interferon Type I; Interferons; Keratinocytes; Lupus Erythematosus, Systemic; Mesangial Cells; Mice, Inbred C57BL; Mice, Mutant Strains; Receptors, Interferon; Signal Transduction; Toll-Like Receptor 7; Interferon Lambda
PubMed: 32094169
DOI: 10.1073/pnas.1916897117 -
Neurochemical Research Sep 2017Microglia, the resident immune cells of the CNS, are primary regulators of the neuroimmune response to injury. Type I interferons (IFNs), including the IFNαs and IFNβ,... (Review)
Review
Microglia, the resident immune cells of the CNS, are primary regulators of the neuroimmune response to injury. Type I interferons (IFNs), including the IFNαs and IFNβ, are key cytokines in the innate immune system. Their activity is implicated in the regulation of microglial function both during development and in response to neuroinflammation, ischemia, and neurodegeneration. Data from numerous studies in multiple sclerosis (MS) and stroke suggest that type I IFNs can modulate the microglial phenotype, influence the overall neuroimmune milieu, regulate phagocytosis, and affect blood-brain barrier integrity. All of these IFN-induced effects result in numerous downstream consequences on white matter pathology and microglial reactivity. Dysregulation of IFN signaling in mouse models with genetic deficiency in ubiquitin specific protease 18 (USP18) leads to a severe neurological phenotype and neuropathological changes that include white matter microgliosis and pro-inflammatory gene expression in dystrophic microglia. A class of genetic disorders in humans, referred to as pseudo-TORCH syndrome (PTS) for the clinical resemblance to infection-induced TORCH syndrome, also show dysregulation of IFN signaling, which leads to severe neurological developmental disease. In these disorders, the excessive activation of IFN signaling during CNS development results in a destructive interferonopathy with similar induction of microglial dysfunction as seen in USP18 deficient mice. Other recent studies implicate "microgliopathies" more broadly in neurological disorders including Alzheimer's disease (AD) and MS, suggesting that microglia are a potential therapeutic target for disease prevention and/or treatment, with interferon signaling playing a key role in regulating the microglial phenotype.
Topics: Animals; Humans; Interferon Inducers; Interferon Type I; Microglia; Nervous System Diseases; Poly I-C; Signal Transduction; White Matter
PubMed: 28540600
DOI: 10.1007/s11064-017-2307-8 -
International Journal of Medical... 2020Since the end of 2019, a new type of coronavirus pneumonia (COVID-19) caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has been spreading... (Review)
Review
Since the end of 2019, a new type of coronavirus pneumonia (COVID-19) caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has been spreading rapidly throughout the world. Previously, there were two outbreaks of severe coronavirus caused by different coronaviruses worldwide, namely Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). This article introduced the origin, virological characteristics and epidemiological overview of SARS-CoV-2, reviewed the currently known drugs that may prevent and treat coronavirus, explained the characteristics of the new coronavirus and provided novel information for the prevention and treatment of COVID-19.
Topics: Amides; Antibodies, Monoclonal; Antiviral Agents; Betacoronavirus; COVID-19; Chloroquine; Chlorpromazine; Coronavirus; Coronavirus Infections; Cyclophilins; Drug Development; Drug Repositioning; Drugs, Chinese Herbal; Endocytosis; Humans; Immune Sera; Interferon Inducers; Nucleic Acid Synthesis Inhibitors; Pandemics; Pneumonia, Viral; Pyrazines; Resveratrol; SARS-CoV-2; Viral Vaccines; COVID-19 Drug Treatment
PubMed: 32714083
DOI: 10.7150/ijms.47836 -
Virology Apr 2007Mice are used as models for western equine encephalitis virus (WEEV) infection, but high mortality is generally only seen with intracranial or intranasal challenge,...
Mice are used as models for western equine encephalitis virus (WEEV) infection, but high mortality is generally only seen with intracranial or intranasal challenge, while peripheral inoculation results in approximately 50% mortality and is not dose-dependent. Hamsters were therefore studied as a model for WEEV infection. Hamsters were highly sensitive to intraperitoneal (i.p.) infection with WEEV. Disease progression was rapid, and virus titers in serum, brain, liver, and kidney of infected hamsters peaked between 2 and 4 days post-virus inoculation (dpi). Foci of virus infection were detected in neurons of the cerebral cortex and midbrain. Pre-treatment i.p. with either interferon alfacon-1 (5 microg/kg/day) or with Ampligen (3.2 mg/kg/day) resulted in complete survival, reduced brain titers, and improved weight gain. This model of WEEV infection in hamsters appears to serve as a suitable model for the evaluation of potential therapeutic agents for the treatment of WEE disease.
Topics: Animals; Antiviral Agents; Body Weight; Brain; Cerebral Cortex; Cricetinae; Disease Models, Animal; Encephalitis Virus, Western Equine; Encephalomyelitis, Equine; Interferon Inducers; Interferon Type I; Interferon-alpha; Kidney; Liver; Mesencephalon; Mesocricetus; Poly I-C; Poly U; Recombinant Proteins; Serum
PubMed: 17118420
DOI: 10.1016/j.virol.2006.10.031 -
British Medical Journal Jan 1977
Topics: Humans; Interferon Inducers; Interferons; Virus Diseases; Virus Replication
PubMed: 832014
DOI: No ID Found -
Nature Reviews. Microbiology Jun 2016The co-evolution of viruses with their hosts has led to the emergence of viral pathogens that are adept at evading or actively suppressing host immunity. Pattern... (Review)
Review
The co-evolution of viruses with their hosts has led to the emergence of viral pathogens that are adept at evading or actively suppressing host immunity. Pattern recognition receptors (PRRs) are key components of antiviral immunity that detect conserved molecular features of viral pathogens and initiate signalling that results in the expression of antiviral genes. In this Review, we discuss the strategies that viruses use to escape immune surveillance by key intracellular sensors of viral RNA or DNA, with a focus on RIG-I-like receptors (RLRs), cyclic GMP-AMP synthase (cGAS) and interferon-γ (IFNγ)-inducible protein 16 (IFI16). Such viral strategies include the sequestration or modification of viral nucleic acids, interference with specific post-translational modifications of PRRs or their adaptor proteins, the degradation or cleavage of PRRs or their adaptors, and the sequestration or relocalization of PRRs. An understanding of viral immune-evasion mechanisms at the molecular level may guide the development of vaccines and antivirals.
Topics: Animals; Cytoplasm; DEAD Box Protein 58; DNA, Viral; Humans; Immune Evasion; Immunity, Innate; Inflammasomes; Interferon Inducers; Nuclear Proteins; Phosphoproteins; Protein Processing, Post-Translational; RNA, Viral; Receptors, Pattern Recognition; Signal Transduction; Viruses
PubMed: 27174148
DOI: 10.1038/nrmicro.2016.45 -
Design, synthesis, and biological evaluation of N-arylpiperazine derivatives as interferon inducers.Bioorganic & Medicinal Chemistry Letters Dec 2020Type I Interferon (IFN) signaling plays an important role in the immune defense system against virus infection and in the innate immune response, thus IFNs are widely...
Type I Interferon (IFN) signaling plays an important role in the immune defense system against virus infection and in the innate immune response, thus IFNs are widely used as anti-viral agents and treatment for immune disorder or cancer. However, there is a growing demand for novel small-molecule IFN inducer due to tolerance, toxicity, or short duration of action following direct administration of IFNs. In this study, we assessed arylpiperazine (ARP) as a new core skeleton of IFN inducer. To investigate structure-activity relationship, we designed and synthesized a series of ARP analogues and evaluated the ability to stimulate IFN response in THP-1 human monocyte cells. Compound 5i was identified as a potent type I IFN inducer as it significantly increased cytokine secretion and increased expression of various IFN-stimulating genes which are representative biomarkers of type I IFN pathway. Our results suggested a beneficial therapeutic potential of 5i as an anti-viral agent.
Topics: Drug Design; Humans; Immunity, Innate; Interferon Inducers; Interferon Type I; Monocytes; Piperazines; THP-1 Cells
PubMed: 33075488
DOI: 10.1016/j.bmcl.2020.127613 -
Annual Review of Microbiology 1975
Topics: Animals; Cells; Humans; Interferon Inducers; Interferons; Protein Biosynthesis; Transcription, Genetic; Viruses
PubMed: 1180510
DOI: 10.1146/annurev.mi.29.100175.001023 -
Antiviral Chemistry & Chemotherapy Mar 2004The recent West Nile virus (WNV) outbreak in the United States has increased the need to identify effective therapies. Studies were conducted in cell culture and in...
The recent West Nile virus (WNV) outbreak in the United States has increased the need to identify effective therapies. Studies were conducted in cell culture and in rodent animal models to determine the efficacy of interferon-alpha (IFN-alpha), interferon (IFN) inducers and ribavirin, alone or in combination with IFN, in treating WNV. Intraperitoneal injection of IFN-alpha B/D (qd for 7 days), polyI-polyC(12)U [Ampligen (every other day for 7 days)] and topically applied imiquimod (qd for 7 days), administered from 1 day before viral challenge, were effective in protecting, respectively, 100%, 100% and 70% of BALB/c mice from mortality induced by subcutaneous injection of WNV. When IFN-alpha B/D or Ampligen treatments were delayed to 4-6 h before viral challenge in mice, efficacy was greatly diminished. Infected Syrian golden hamsters treated with interferon alphacon-1 (Infergen) and Ampligen 4-6 h before viral challenge gained more weight and had a greater survival than saline-treated animals. A combination study of subcutaneously administered Infergen (5 to 0.05 microg/kg/day) and ribavirin (75 to 7.5 mg/kg/day) in >7 week old hamsters demonstrated that Infergen was slightly efficacious in reducing mortality and disease signs; however, it was not synergistic in its antiviral effects when combined with ribavirin. Ribavirin treatment alone increased mortality of infected hamsters. The reduced mortality correlated with reduced plasma viraemia. Since WNV-infected patients have already been treated with IFN and ribavirin and future clinical trials have been suggested, this first report of IFN alone or in combination with ribavirin in WNV-infected animal models might provide useful information for subsequent treatment of patients.
Topics: Aminoquinolines; Animals; Cells, Cultured; Cricetinae; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Therapy, Combination; Humans; Imiquimod; Interferon Inducers; Interferon Type I; Interferon-alpha; Interferons; Mice; Mice, Inbred BALB C; Motor Activity; Poly I-C; Poly U; Recombinant Proteins; Ribavirin; Survival Rate; Time Factors; West Nile Fever; West Nile virus
PubMed: 15185728
DOI: 10.1177/095632020401500202