scholarly journals Filovirus VP24 Proteins Differentially Regulate RIG-I and MDA5-Dependent Type I and III Interferon Promoter Activation

2022 ◽  
Vol 12 ◽  
Author(s):  
Felix B. He ◽  
Hira Khan ◽  
Moona Huttunen ◽  
Pekka Kolehmainen ◽  
Krister Melén ◽  
...  
Keyword(s):  
Type I ◽  
Promoter Activation ◽  
African Countries ◽  
Highly Pathogenic ◽  
Inhibitory Mechanisms ◽  
New Information ◽  
Pathogenic Viruses ◽  
Global Threat ◽  
Antigen 5 ◽  
Highly Virulent

Filovirus family consists of highly pathogenic viruses that have caused fatal outbreaks especially in many African countries. Previously, research focus has been on Ebola, Sudan and Marburg viruses leaving other filoviruses less well studied. Filoviruses, in general, pose a significant global threat since they are highly virulent and potentially transmissible between humans causing sporadic infections and local or widespread epidemics. Filoviruses have the ability to downregulate innate immunity, and especially viral protein 24 (VP24), VP35 and VP40 have variably been shown to interfere with interferon (IFN) gene expression and signaling. Here we systematically analyzed the ability of VP24 proteins of nine filovirus family members to interfere with retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated antigen 5 (MDA5) induced IFN-β and IFN-λ1 promoter activation. All VP24 proteins were localized both in the cell cytoplasm and nucleus in variable amounts. VP24 proteins of Zaire and Sudan ebolaviruses, Lloviu, Taï Forest, Reston, Marburg and Bundibugyo viruses (EBOV, SUDV, LLOV, TAFV, RESTV, MARV and BDBV, respectively) were found to inhibit both RIG-I and MDA5 stimulated IFN-β and IFN-λ1 promoter activation. The inhibition takes place downstream of interferon regulatory factor 3 phosphorylation suggesting the inhibition to occur in the nucleus. VP24 proteins of Mengla (MLAV) or Bombali viruses (BOMV) did not inhibit IFN-β or IFN-λ1 promoter activation. Six ebolavirus VP24s and Lloviu VP24 bound tightly, whereas MARV and MLAV VP24s bound weakly, to importin α5, the subtype that regulates the nuclear import of STAT complexes. MARV and MLAV VP24 binding to importin α5 was very weak. Our data provides new information on the innate immune inhibitory mechanisms of filovirus VP24 proteins, which may contribute to the pathogenesis of filovirus infections.

scholarly journals SARS-CoV-2 Cellular Infection and Therapeutic Opportunities: Lessons Learned from Ebola Virus

Membranes ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 64
Author(s):  
Jordana Muñoz-Basagoiti ◽  
Daniel Perez-Zsolt ◽  
Jorge Carrillo ◽  
Julià Blanco ◽  
Bonaventura Clotet ◽  
...  
Keyword(s):  
Viral Entry ◽  
Ebola Virus ◽  
Lessons Learned ◽  
Productive Infection ◽  
Target Cells ◽  
Emerging Viruses ◽  
Highly Pathogenic ◽  
Life Threatening ◽  
Pathogenic Viruses ◽  
Cellular Machinery

Viruses rely on the cellular machinery to replicate and propagate within newly infected individuals. Thus, viral entry into the host cell sets up the stage for productive infection and disease progression. Different viruses exploit distinct cellular receptors for viral entry; however, numerous viral internalization mechanisms are shared by very diverse viral families. Such is the case of Ebola virus (EBOV), which belongs to the filoviridae family, and the recently emerged coronavirus SARS-CoV-2. These two highly pathogenic viruses can exploit very similar endocytic routes to productively infect target cells. This convergence has sped up the experimental assessment of clinical therapies against SARS-CoV-2 previously found to be effective for EBOV, and facilitated their expedited clinical testing. Here we review how the viral entry processes and subsequent replication and egress strategies of EBOV and SARS-CoV-2 can overlap, and how our previous knowledge on antivirals, antibodies, and vaccines against EBOV has boosted the search for effective countermeasures against the new coronavirus. As preparedness is key to contain forthcoming pandemics, lessons learned over the years by combating life-threatening viruses should help us to quickly deploy effective tools against novel emerging viruses.

Antivirals with common targets against highly pathogenic viruses

Cell ◽  
2021 ◽  
Vol 184 (6) ◽  
pp. 1604-1620
Author(s):  
Lu Lu ◽  
Shan Su ◽  
Haitao Yang ◽  
Shibo Jiang
Keyword(s):  
Highly Pathogenic ◽  
Pathogenic Viruses

scholarly journals The virome of German bats: comparing virus discovery approaches

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Claudia Kohl ◽  
Annika Brinkmann ◽  
Aleksandar Radonić ◽  
Piotr Wojtek Dabrowski ◽  
Kristin Mühldorfer ◽  
...  
Keyword(s):  
Virus Detection ◽  
Detection Methods ◽  
Single Type ◽  
Metagenomic Sequencing ◽  
Virus Discovery ◽  
Highly Pathogenic ◽  
Pcr Screening ◽  
Specific Pcr ◽  
Pathogenic Viruses ◽  
Viral Sequences

AbstractBats are known to be reservoirs of several highly pathogenic viruses. Hence, the interest in bat virus discovery has been increasing rapidly over the last decade. So far, most studies have focused on a single type of virus detection method, either PCR, virus isolation or virome sequencing. Here we present a comprehensive approach in virus discovery, using all three discovery methods on samples from the same bats. By family-specific PCR screening we found sequences of paramyxoviruses, adenoviruses, herpesviruses and one coronavirus. By cell culture we isolated a novel bat adenovirus and bat orthoreovirus. Virome sequencing revealed viral sequences of ten different virus families and orders: three bat nairoviruses, three phenuiviruses, one orbivirus, one rotavirus, one orthoreovirus, one mononegavirus, five parvoviruses, seven picornaviruses, three retroviruses, one totivirus and two thymoviruses were discovered. Of all viruses identified by family-specific PCR in the original samples, none was found by metagenomic sequencing. Vice versa, none of the viruses found by the metagenomic virome approach was detected by family-specific PCRs targeting the same family. The discrepancy of detected viruses by different detection approaches suggests that a combined approach using different detection methods is necessary for virus discovery studies.

scholarly journals New Pyridone-Based Derivatives as Cannabinoid Receptor Type 2 Agonists

2021 ◽  
Vol 22 (20) ◽  
pp. 11212
Author(s):  
Manuel Faúndez-Parraguez ◽  
Carlos Alarcón-Miranda ◽  
Young Hwa Cho ◽  
Hernán Pessoa-Mahana ◽  
Carlos Gallardo-Garrido ◽  
...  
Keyword(s):  
Cannabinoid Receptor ◽  
Docking Studies ◽  
Receptor Type ◽  
Intracellular Camp ◽  
Type I ◽  
Type Ii ◽  
New Information ◽  
Starting Point ◽  
Inflammatory Processes

The activation of the human cannabinoid receptor type II (CB2R) is known to mediate analgesic and anti-inflammatory processes without the central adverse effects related to cannabinoid receptor type I (CB1R). In this work we describe the synthesis and evaluation of a novel series of N-aryl-2-pyridone-3-carboxamide derivatives tested as human cannabinoid receptor type II (CB2R) agonists. Different cycloalkanes linked to the N-aryl pyridone by an amide group displayed CB2R agonist activity as determined by intracellular [cAMP] levels. The most promising compound 8d exhibited a non-toxic profile and similar potency (EC50 = 112 nM) to endogenous agonists Anandamide (AEA) and 2-Arachidonoylglycerol (2-AG) providing new information for the development of small molecules activating CB2R. Molecular docking studies showed a binding pose consistent with two structurally different agonists WIN-55212-2 and AM12033 and suggested structural requirements on the pyridone substituents that can satisfy the orthosteric pocket and induce an agonist response. Our results provide additional evidence to support the 2-pyridone ring as a suitable scaffold for the design of CB2R agonists and represent a starting point for further optimization and development of novel compounds for the treatment of pain and inflammation.

scholarly journals Investigation of Various Diseases Occurred in Poultry and Management Strategies for Eradication

2018 ◽  
Vol 7 (3.1) ◽  
pp. 150
Author(s):  
Sunil Patil ◽  
Chhanwal I.L
Keyword(s):  
Family Income ◽  
Migratory Birds ◽  
Management Practice ◽  
Management Strategies ◽  
Farm Management ◽  
Poultry Meat ◽  
Highly Pathogenic ◽  
The World ◽  
Pathogenic Viruses ◽  
Poultry Disease

Poultry plays a significant role in the Indian economy. Around 60 billion chickens are raised per annum as a basis of food for both their eggs and meat. Poultry meat is in significant source of minerals, protein and various vitamins to balance the diet of human. Broiler farming is an important source of family income depending on size of the farm. Chicken farming in Commercial way is the most fruitful business in India and all around the world. Proper farm management practice and care of birds will result in decent profit in a short span of time. In this paper, we are discussing various diseases caused to poultry hen and their preventing or treating methods. Our results shows that some of disease cannot be cured and only it can be prevented. Spreading of disease with the help of contaminated equipment and infected poultry trade is measured as foremost means of spreading of poultry disease. In some countries migratory birds have also been foremost means of spreading of poultry disease like highly pathogenic viruses. 

scholarly journals Antimicrobial Resistance and Genomic Characterization of OXA-48- and CTX-M-15-Co-Producing Hypervirulent Klebsiella pneumoniae ST23 Recovered from Nosocomial Outbreak

Antibiotics ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 862
Author(s):  
Elvira Shaidullina ◽  
Andrey Shelenkov ◽  
Yuri Yanushevich ◽  
Yulia Mikhaylova ◽  
Dmitriy Shagin ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Illumina Miseq ◽  
Type I ◽  
Nosocomial Outbreak ◽  
Recent Emergence ◽  
Genomic Characterization ◽  
Global Threat ◽  
High Level ◽  
Sepsis And Septic Shock

Multidrug resistance (MDR) and hypervirulence (hv) have been long considered distinct evolutionary traits for Klebsiella pneumoniae (Kp), a versatile human pathogen. The recent emergence of Kp strains combining these traits poses a serious global threat. In this article, we describe the phenotypic and genomic characteristics of an MDR hvKp isolate, MAR14-456, representative of a nosocomial outbreak in Moscow, Russia, that was recovered from a postoperative wound in a patient who later developed multiple abscesses, fatal sepsis, and septic shock. Broth microdilution testing revealed decreased susceptibility of MAR14-456 to carbapenems (MICs 0.5–2 mg/L) and a high-level resistance to most β-lactams, β-lactam-β-lactamase-inhibitor combinations, and non-β-lactam antibiotics, except ceftazidime-avibactam, amikacin, tigecycline, and colistin. Whole-genome sequencing using Illumina MiSeq and ONT MinION systems allowed to identify and completely assemble two conjugative resistance plasmids, a typical ‘European’ epidemic IncL/M plasmid that carries the gene of OXA-48 carbapenemase, and an IncFIIK plasmid that carries the gene of CTX-M-15 ESBL and other resistance genes. MLST profile, capsular, lipopolysaccharide, virulence genes encoded on chromosome and IncHI1B/FIB plasmid, and the presence of apparently functional type I-E* CRISPR-Cas system were all characteristic of hvKp ST23, serotype K1-O1v2. Phylogenetic analysis showed the closest relatedness of MAR14-456 to ST23 isolates from China. This report highlights the threat of multiple resistance acquisition by hvKp strain and its spread as a nosocomial pathogen.

scholarly journals Effective screening of SARS-CoV-2 neutralizing antibodies in patient serum using lentivirus particles pseudotyped with SARS-CoV-2 spike glycoprotein

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ritesh Tandon ◽  
Dipanwita Mitra ◽  
Poonam Sharma ◽  
Martin G. McCandless ◽  
Stephen J. Stray ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Neutralizing Antibodies ◽  
Transduction Efficiency ◽  
Pseudotyped Virus ◽  
Spike Glycoprotein ◽  
Highly Pathogenic ◽  
Mammalian Cell Lines ◽  
Serological Studies ◽  
Pathogenic Viruses ◽  
Vesicular Stomatitis

Abstract Pseuodotyped particles have significant importance and use in virology as tools for studying the biology of highly pathogenic viruses in a lower biosafety environment. The biological, chemical, and serological studies of the recently emerged SARS-CoV-2 will be greatly aided by the development and optimization of a suitable pseudotyping system. Here, we pseudotyped the SARS-CoV-2 Spike glycoprotein (SPG) on a traditional retroviral (MMLV) as well as a third generation lentiviral (pLV) vector and tested the transduction efficiency in several mammalian cell lines expressing SARS-CoV-2 receptor hACE2. While MMLV pseudotyped the vesicular stomatitis virus G glycoprotein (VSV-G) efficiently, it could not pseudotype the full-length SPG. In contrast, pLV pseudotyped both glycoproteins efficiently; however, much higher titers of pLV-G particles were produced. Among all the tested mammalian cells, 293Ts expressing hACE2 were most efficiently transduced using the pLV-S system. The pLV-S particles were efficiently neutralized by diluted serum (>:640) from recently recovered COVID-19 patients who showed high SARS-CoV-2 specific IgM and IgG levels. In summary, pLV-S pseudotyped virus provides a valid screening tool for the presence of anti SARS-CoV-2 specific neutralizing antibodies in convalescent patient serum.

scholarly journals Differential Immune Responses to Hemorrhagic Fever-Causing Arenaviruses

Vaccines ◽  
2019 ◽  
Vol 7 (4) ◽  
pp. 138 ◽  
Author(s):  
Mantlo ◽  
Paessler ◽  
Huang
Keyword(s):  
Clinical Importance ◽  
Hemorrhagic Fever ◽  
Lassa Fever ◽  
Innate Immune ◽  
Host Immune System ◽  
Lassa Virus ◽  
Type I ◽  
Highly Pathogenic ◽  
The Family ◽  
Pro Inflammatory Cytokines

The family Arenaviridae contains several pathogens of major clinical importance. The Old World (OW) arenavirus Lassa virus is endemic in West Africa and is estimated to cause up to 300,000 infections each year. The New World (NW) arenaviruses Junín and Machupo periodically cause hemorrhagic fever outbreaks in South America. While these arenaviruses are highly pathogenic in humans, recent evidence indicates that pathogenic OW and NW arenaviruses interact with the host immune system differently, which may have differential impacts on viral pathogenesis. Severe Lassa fever cases are characterized by profound immunosuppression. In contrast, pathogenic NW arenavirus infections are accompanied by elevated levels of Type I interferon and pro-inflammatory cytokines. This review aims to summarize recent findings about interactions of these pathogenic arenaviruses with the innate immune machinery and the subsequent effects on adaptive immunity, which may inform the development of vaccines and therapeutics against arenavirus infections.

scholarly journals Evaluation of a Single-Dose Nucleoside-Modified Messenger RNA Vaccine Encoding Hendra Virus-Soluble Glycoprotein Against Lethal Nipah virus Challenge in Syrian Hamsters

2019 ◽  
Vol 221 (Supplement_4) ◽  
pp. S493-S498 ◽  
Author(s):  
Michael K Lo ◽  
Jessica R Spengler ◽  
Stephen R Welch ◽  
Jessica R Harmon ◽  
JoAnn D Coleman-McCray ◽  
...  
Keyword(s):  
Single Dose ◽  
Immune Responses ◽  
Messenger Rna ◽  
Nipah Virus ◽  
Hendra Virus ◽  
Highly Pathogenic ◽  
Syrian Hamsters ◽  
Virus Challenge ◽  
Pathogenic Viruses ◽  
Rna Vaccine

Abstract In the absence of approved vaccines and therapeutics for use in humans, Nipah virus (NiV) continues to cause fatal outbreaks of encephalitis and respiratory disease in Bangladesh and India on a near-annual basis. We determined that a single dose of a lipid nanoparticle nucleoside-modified messenger RNA vaccine encoding the soluble Hendra virus glycoprotein protected up to 70% of Syrian hamsters from lethal NiV challenge, despite animals having suboptimally primed immune responses before challenge. These data provide a foundation from which to optimize future messenger RNA vaccination studies against NiV and other highly pathogenic viruses.

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