scholarly journals How Innate Immune Mechanisms Contribute to Antibody-Enhanced Viral Infections

2010 ◽  
Vol 17 (12) ◽  
pp. 1829-1835 ◽  
Author(s):  
Sukathida Ubol ◽  
Scott B. Halstead
Keyword(s):  
Dengue Virus ◽  
Measles Virus ◽  
Viral Infections ◽  
Natural Infection ◽  
Innate Immune ◽  
Th2 Cells ◽  
Wild Type Virus ◽  
Severe Dengue ◽  
Syncytial Virus

ABSTRACT Preexisting antibodies may enhance viral infections. In dengue, nonneutralizing antibodies raised by natural infection with one of four dengue viruses (DENVs) may enhance infection with a different virus by a process we term “intrinsic antibody-dependent enhancement” (iADE). In addition, nonprotective antibodies raised by formalin-inactivated respiratory syncytial virus (RSV) and measles virus vaccines have led to enhanced disease during breakthrough infections. Infections under iADE conditions not only facilitate the process of viral entry into monocytes and macrophages but also modify innate and adaptive intracellular antiviral mechanisms, suppressing type 1 interferon (IFN) production and resulting in enhanced DENV replication. The suppression observed in vitro has been documented in patients with severe (dengue hemorrhagic fever [DHF]) but not in patient with mild (dengue fever [DF]) secondary dengue virus infections. Important veterinary viral infections also may exhibit iADE. It is thought that use of formalin deconforms viral epitopes of RSV, resulting in poor Toll-like receptor (TLR) stimulation; suboptimal maturation of dendritic cells with reduced production of activation factors CD40, CD80, and CD86; decreased germinal center formation in lymph nodes; and the production of nonprotective antibodies. These antibodies fail to neutralize RSV, allowing replication with secondary stimulation of RSV-primed Th2 cells producing more low-avidity antibody, resulting in immune complexes deposited into affected tissue. However, when formalin-inactivated RSV was administered with a TLR agonist to mice, they were protected against wild-type virus challenge. Safe and effective vaccines against RSV/measles virus and dengue virus may benefit from a better understanding of how innate immune responses can promote production of protective antibodies.

scholarly journals The TLR4 Agonist Immunomax Affects the Phenotype of Mouse Lung Macrophages during Respiratory Syncytial Virus Infection

Acta Naturae ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 95-99 ◽  
Author(s):  
A. A. Nikonova ◽  
A. V. Pichugin ◽  
M. M. Chulkina ◽  
E. S. Lebedeva ◽  
A. R. Gaisina ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Viral Infections ◽  
Th2 Cells ◽  
Mouse Lung ◽  
Inos Mrna ◽  
Mouse Bone Marrow ◽  
Tlr4 Agonist ◽  
Syncytial Virus

In the study, the effect of the TLR4 agonist Immunomax was investigated in vitro and in vivo. In particular, Immunomax was shown to polarize mouse bone marrow macrophages from the M0 and M2 states into the M1 state (ARG1 and iNOS mRNA expression levels were used to identify the mouse M1 and M2 phenotypes). Next, we investigated the prophylactic antiviral effect of Immunomax in both a model of mouse respiratory syncytial virus (RSV) infection and a model of RSV-induced bronchial asthma (BA) exacerbation. In the experiment with RSV-induced BA exacerbation, Immunomax-treated mice were characterized by a significant decrease of the viral load in lung homogenates, an increased amount of M1 macrophages in the lung, a tendency toward Th2-dependent ovalbumin-specific IgG1 antibodies decrease in blood serum, a significant increase in RSV-activated CD4+ T cells secreting IFN (Th1 cells), and a simultaneous significant decrease in the amount of CD4+ cells secreting IL-4 (Th2 cells) in the mouse spleen, which were detected by ELISPOT 1.5 months after experiment. These findings suggest that treatment with the TLR4 agonist Immunomax polarizes the immune response towards antiviral Th1 and may be used for short-term antiviral prophylaxis to prevent acute respiratory viral infections in asthmatics.

scholarly journals Effect of viral infection on brain functions and Psychological Impact of the COVID-19 on our thinking and mood

2021 ◽  
Author(s):  
Javeria Maqbool ◽  
Azhar Rasul ◽  
Javed Iqbal ◽  
Haseeb Anwar ◽  
Ali Imran ◽  
...  
Keyword(s):  
Measles Virus ◽  
Viral Infections ◽  
Positive Impact ◽  
Clinical Manifestations ◽  
Behavioral Changes ◽  
Panic Attacks ◽  
Google Scholar ◽  
Modern World ◽  
Brain Functions ◽  
Syncytial Virus

Background: Viral infections such as measles virus (MV), herpes virus, and human immunodeficiency virus (HIV) can lead to transient or permanent neurological or psychiatric dysfunction. However, respiratory system affecting viruses have appeared as an unbeatable challenge to the modern world. They include the human respiratory syncytial virus (hRSV), the influenza virus (IV), and the coronavirus (CoV). They cause acute respiratory infections mainly children under 5 years old and also the elderly. The most frequent clinical manifestations are febrile or afebrile seizures, status epilepticus, encephalopathies, and encephalitis. Objective: The objective of this review is to assess the effect of COVID-19 on our mood and thinking during this pandemic. Method: We reviewed the literature using different databases e.g., Google Scholar, PubMed, and Science direct etc. Results: Viral Infections badly affect the nervous system functions and ultimate can lead to the onset of neurological and psychological illnesses. Conclusion: COVID-19 is somehow causing depression, anxiety, panic attacks, and stress. As a consequence, social distancing has increased that has ultimately modified our thinking style, mood and has lead to the psychological, emotional and behavioral changes. Review Criteria We reviewed the literature using different databases e.g., Google Scholar, PubMed, etc. from 1997 to 2021 without language limitations. Message for the clinic It is clear that COVID-19 causes cardiac, respiratory, renal, and gastrointestinal dysfunctions and has also a direct effect on brain functioning resulting in psychological and behavioral changes. Along with other dysfunctions, it has severely affected the living style of people and brought depression, anxiety, panic attacks, loneliness, and self-deprecation. It is highly recommended that while treating such patients, all these aspects should be kept in mind. Hence, not only medication can ameliorate the side impacts of this infection but counseling is another tool to bring positive impact in those respondents.

Platelets Modulate Innate Immune Response Against Human Respiratory Syncytial Virus In Vitro

2017 ◽  
Vol 30 (8) ◽  
pp. 576-581 ◽  
Author(s):  
Vesla I. Kullaya ◽  
Quirijn de Mast ◽  
Andre van der Ven ◽  
Hicham elMoussaoui ◽  
Gibson Kibiki ◽  
...  
Keyword(s):  
Immune Response ◽  
Respiratory Syncytial Virus ◽  
Innate Immune Response ◽  
Human Respiratory Syncytial Virus ◽  
Innate Immune ◽  
Syncytial Virus

scholarly journals Modified cyclodextrins as broad-spectrum antivirals

2020 ◽  
Vol 6 (5) ◽  
pp. eaax9318 ◽  
Author(s):  
Samuel T. Jones ◽  
Valeria Cagno ◽  
Matej Janeček ◽  
Daniel Ortiz ◽  
Natalia Gasilova ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Viral Infections ◽  
Ex Vivo ◽  
Vaginal Tissue ◽  
Modified Cyclodextrins ◽  
Culture Models ◽  
Heparan Sulfates ◽  
Syncytial Virus ◽  
Simplex Virus

Viral infections kill millions of people and new antivirals are needed. Nontoxic drugs that irreversibly inhibit viruses (virucidal) are postulated to be ideal. Unfortunately, all virucidal molecules described to date are cytotoxic. We recently developed nontoxic, broad-spectrum virucidal gold nanoparticles. Here, we develop further the concept and describe cyclodextrins, modified with mercaptoundecane sulfonic acids, to mimic heparan sulfates and to provide the key nontoxic virucidal action. We show that the resulting macromolecules are broad-spectrum, biocompatible, and virucidal at micromolar concentrations in vitro against many viruses [including herpes simplex virus (HSV), respiratory syncytial virus (RSV), dengue virus, and Zika virus]. They are effective ex vivo against both laboratory and clinical strains of RSV and HSV-2 in respiratory and vaginal tissue culture models, respectively. Additionally, they are effective when administrated in mice before intravaginal HSV-2 inoculation. Lastly, they pass a mutation resistance test that the currently available anti-HSV drug (acyclovir) fails.

scholarly journals Coxiella burnetii Interaction with Neutrophils and MacrophagesIn Vitroand in SCID Mice following Aerosol Infection

2013 ◽  
Vol 81 (12) ◽  
pp. 4604-4614 ◽  
Author(s):  
Alexandra Elliott ◽  
Ying Peng ◽  
Guoquan Zhang
Keyword(s):  
Immune Response ◽  
Coxiella Burnetii ◽  
Q Fever ◽  
Natural Infection ◽  
Scid Mice ◽  
Innate Immune ◽  
Content Type ◽  
Aerosol Infection

ABSTRACTCoxiella burnetiiis an obligate intracellular bacterium that causes acute and chronic Q fever in humans. Human Q fever is mainly transmitted by aerosol infection. However, there is a fundamental gap in the knowledge regarding the mechanisms of pulmonary immunity againstC. burnetiiinfection. This study focused on understanding the interaction betweenC. burnetiiand innate immune cellsin vitroandin vivo. Both virulentC. burnetiiNine Mile phase I (NMI) and avirulent Nine Mile phase II (NMII) were able to infect neutrophils, while the infection rates were lower than 29%, suggesting thatC. burnetiican infect neutrophils, but infection is limited. Interestingly,C. burnetiiinside neutrophils can infect and replicate within macrophages, suggesting that neutrophils cannot killC. burnetiiandC. burnetiimay be using infection of neutrophils as an evasive strategy to infect macrophages. To elucidate the mechanisms of the innate immune response toC. burnetiinatural infection, SCID mice were exposed to aerosolizedC. burnetii. Surprisingly, neutrophil influx into the lungs was delayed until day 7 postinfection in both NMI- and NMII-infected mice. This result suggests that neutrophils may play a unique role in the early immune response against aerosolizedC. burnetii. Studying the interaction betweenC. burnetiiand the innate immune system can provide a model system for understanding how the bacteria evade early immune responses to cause infection.

scholarly journals Antiviral Activity of Favipiravir (T-705) against a Broad Range of ParamyxovirusesIn Vitroand against Human Metapneumovirus in Hamsters

2016 ◽  
Vol 60 (8) ◽  
pp. 4620-4629 ◽  
Author(s):  
D. Jochmans ◽  
S. van Nieuwkoop ◽  
S. L. Smits ◽  
J. Neyts ◽  
R. A. M. Fouchier ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Measles Virus ◽  
Rna Virus ◽  
Antiviral Drug ◽  
Specific Effect ◽  
Human Metapneumovirus ◽  
Drug Candidate ◽  
Emerging Viruses ◽  
Syncytial Virus

ABSTRACTThe clinical impact of infections with respiratory viruses belonging to the familyParamyxoviridaeargues for the development of antiviral therapies with broad-spectrum activity. Favipiravir (T-705) has demonstrated potent antiviral activity against multiple RNA virus families and is presently in clinical evaluation for the treatment of influenza. Here we demonstratein vitroactivity of T-705 against the paramyxoviruses human metapneumovirus (HMPV), respiratory syncytial virus, human parainfluenza virus, measles virus, Newcastle disease virus, and avian metapneumovirus. In addition, we demonstrate activity against HMPV in hamsters. T-705 treatment inhibited replication of all paramyxoviruses testedin vitro, with 90% effective concentration (EC90) values of 8 to 40 μM. Treatment of HMPV-challenged hamsters with T-705 at 200 mg/kg of body weight/day resulted in 100% protection from infection of the lungs. In all treated and challenged animals, viral RNA remained detectable in the respiratory tract. The observation that T-705 treatment had a significant effect on infectious viral titers, with a limited effect on viral genome titers, is in agreement with its proposed mode of action of viral mutagenesis. However, next-generation sequencing of viral genomes isolated from treated and challenged hamsters did not reveal (hyper)mutation. Polymerase activity assays revealed a specific effect of T-705 on the activity of the HMPV polymerase. With the reported antiviral activity of T-705 against a broad range of RNA virus families, this small molecule is a promising broad-range antiviral drug candidate for limiting the viral burden of paramyxoviruses and for evaluation for treatment of infections with (re)emerging viruses, such as the henipaviruses.

scholarly journals Highly Potent Host-Specific Small-Molecule Inhibitor of Paramyxovirus and Pneumovirus Replication with High Resistance Barrier

mBio ◽  
2021 ◽  
Author(s):  
Neeta Shrestha ◽  
Flavio Max Gall ◽  
Cyrille Mathieu ◽  
Melanie Michaela Hierweger ◽  
Melanie Brügger ◽  
...  
Keyword(s):  
Measles Virus ◽  
Canine Distemper Virus ◽  
Viral Infections ◽  
Rna Viruses ◽  
Treatment Options ◽  
Nipah Virus ◽  
Canine Distemper ◽  
Molecule Inhibitor ◽  
Syncytial Virus ◽  
Clinically Significant

Measles virus, respiratory syncytial virus, canine distemper virus, and Nipah virus are some of the clinically significant RNA viruses that threaten substantial number of lives each year. Limited to no availability of treatment options for these viral infections makes it arduous to handle the outbreaks.

scholarly journals Antiviral Efficacy of the Anesthetic Propofol against Dengue Virus Infection and Cellular Inflammation

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Ting-Jing Shen ◽  
Chia-Ling Chen ◽  
Ming-Kai Jhan ◽  
Po-Chun Tseng ◽  
Rahmat Dani Satria ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Cell Model ◽  
Antiviral Agents ◽  
Denv Infection ◽  
Severe Dengue ◽  
Cellular Inflammation ◽  
Antiviral Effects ◽  
Endosomal Acidification ◽  
Adults And Children

Propofol, 2,6-diisopropylphenol, is a short-acting intravenous sedative agent used in adults and children. Current studies show its various antimicrobial as well as anti-inflammatory effects. Dengue virus (DENV) is an emerging infectious pathogen transmitted by mosquitoes that causes mild dengue fever and progressive severe dengue diseases. In the absence of safe vaccines and antiviral agents, adjuvant treatments and supportive care are generally administered. This study investigated the antiviral effects of propofol against DENV infection and cellular inflammation by using an in vitro cell model. Treatment with propofol significantly inhibited DENV release 24 h postinfection in BHK-21 cells. Furthermore, it also blocked viral protein expression independent of the translational blockade. Propofol neither caused inhibitory effects on endosomal acidification nor prevented dsRNA replication. Either the proinflammatory TNF-α or the antiviral STAT1 signaling was reduced by propofol treatment. These results provide evidence to show the potential antiviral effects of the sedative propofol against DENV infection and cellular inflammation.

scholarly journals Potential Benefits of Antiviral African Medicinal Plants in the Management of Viral Infections: Systematic Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Tamirat Bekele Beressa ◽  
Serawit Deyno ◽  
Andrew G. Mtewa ◽  
Namuli Aidah ◽  
Naasson Tuyiringire ◽  
...  
Keyword(s):  
Medicinal Plants ◽  
Measles Virus ◽  
Viral Infections ◽  
Yellow Fever Virus ◽  
Rift Valley Fever Virus ◽  
Evidence Synthesis ◽  
Fever Virus ◽  
Antiviral Activities

Background: Viruses cause various human diseases, some of which become pandemic outbreaks. This study synthesized evidence on antiviral medicinal plants in Africa which could potentially be further studied for viral infections including Coronavirus disease 2019 (COVID-19) treatment.Methods: PUBMED, CINAHIL, Scopus, Google Scholar, and Google databases were searched through keywords; antiviral, plant, herb, and Africa were combined using “AND” and “OR”. In-vitro studies, in-vivo studies, or clinical trials on botanical medicine used for the treatment of viruses in Africa were included.Results: Thirty-six studies were included in the evidence synthesis. Three hundred and twenty-eight plants were screened for antiviral activities of which 127 showed noteworthy activities against 25 viral species. These, were Poliovirus (42 plants), HSV (34 plants), Coxsackievirus (16 plants), Rhinovirus (14plants), Influenza (12 plants), Astrovirus (11 plants), SARS-CoV-2 (10 plants), HIV (10 plants), Echovirus (8 plants), Parvovirus (6 plants), Semiliki forest virus (5 plants), Measles virus (5 plants), Hepatitis virus (3 plants), Canine distemper virus (3 plants), Zika virus (2 plants), Vesicular stomatitis virus T2 (2 plants). Feline herpesvirus (FHV-1), Enterovirus, Dengue virus, Ebola virus, Chikungunya virus, Yellow fever virus, Respiratory syncytial virus, Rift Valley fever virus, Human cytomegalovirus each showed sensitivities to one plant.Conclusion: The current study provided a list of African medicinal plants which demonstrated antiviral activities and could potentially be candidates for COVID-19 treatment. However, all studies were preliminary and in vitro screening. Further in vivo studies are required for plant-based management of viral diseases.

scholarly journals Respiratory Syncytial virus NS1 protein targets the transactivator binding domain of MED25

2021 ◽  
Author(s):  
Vincent Basse ◽  
Jiawei Dong ◽  
Andressa Peres de Oliveira ◽  
Pierre-Olivier Vidalain ◽  
Frédéric Tangy ◽  
...  
Keyword(s):  
Immune Response ◽  
Respiratory Syncytial Virus ◽  
Rna Polymerase Ii ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Transactivation Domain ◽  
Ns1 Protein ◽  
Syncytial Virus ◽  
Acid Domain

Respiratory syncytial virus has evolved a unique strategy to evade host immune response by coding for two non-structural proteins NS1 and NS2. Recently it was shown that in infected cells, nuclear NS1 could be involved in transcription regulation of host genes linked to innate immune response, via an interaction with chromatin and the Mediator complex. Here we identified the MED25 Mediator subunit as an NS1 interactor in a yeast two-hybrid screen. We demonstrate that NS1 directly interacts with MED25 in vitro and in cellula, and that this interaction involves the C-terminal α3 helix of NS1 and the MED25 ACID domain. More specifically we showed by NMR that the NS1 α3 sequence primarily binds to the MED25 ACID H2 face, which is a transactivation domain (TAD) binding site for transcription regulators such as ATF6α, a master regulator of ER stress response activated upon viral infection. Moreover, we found out that the NS1 α3 helix could compete with ATF6α TAD binding to MED25. This finding points to a mechanism of NS1 interfering with innate immune response by impairing recruitment by cellular TADs of the Mediator via MED25 and hence transcription of specific genes by RNA polymerase II.

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