scholarly journals Characterization of the Role of Extracellular Vesicles Released from Chicken Tracheal Cells in the Antiviral Responses against Avian Influenza Virus

Membranes ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 53
Author(s):  
Kelsey O’Dowd ◽  
Laura Sánchez ◽  
Jennifer Ben Salem ◽  
Francis Beaudry ◽  
Neda Barjesteh
Keyword(s):  
Influenza Virus ◽  
Avian Influenza ◽  
Avian Influenza Virus ◽  
Extracellular Vesicles ◽  
Respiratory Infections ◽  
Protein Profile ◽  
Antiviral Responses ◽  
Viral Respiratory Infections ◽  
The Impact ◽  
Viral Respiratory

During viral respiratory infections, the innate antiviral response engages a complex network of cells and coordinates the secretion of key antiviral factors, such as cytokines, which requires high levels of regulation and communication. Extracellular vesicles (EVs) are particles released from cells that contain an array of biomolecules, including lipids, proteins, and RNAs. The contents of EVs can be influenced by viral infections and may play a role in the regulation of antiviral responses. We hypothesized that the contents of EVs released from chicken tracheal cells are influenced by viral infection and that these EVs regulate the function of other immune cells, such as macrophages. To this end, we characterized the protein profile of EVs during avian influenza virus (AIV) infection and evaluated the impact of EV stimulation on chicken macrophage functions. A total of 140 differentially expressed proteins were identified upon stimulation with various stimuli. These proteins were shown to be involved in immune responses and cell signaling pathways. In addition, we demonstrated that EVs can activate macrophages. These results suggest that EVs play a role in the induction and modulation of antiviral responses during viral respiratory infections in chickens.

scholarly journals Distinct miRNA Profile of Cellular and Extracellular Vesicles Released from Chicken Tracheal Cells Following Avian Influenza Virus Infection

Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 438
Author(s):  
Kelsey O’Dowd ◽  
Mehdi Emam ◽  
Mohamed Reda El Khili ◽  
Amin Emad ◽  
Eveline M. Ibeagha-Awemu ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Avian Influenza ◽  
Avian Influenza Virus ◽  
Extracellular Vesicles ◽  
Viral Infections ◽  
Influenza Virus Infection ◽  
Influenza Viruses ◽  
Host Cells ◽  
Control Group ◽  
Antiviral Responses

Innate responses provide the first line of defense against viral infections, including the influenza virus at mucosal surfaces. Communication and interaction between different host cells at the early stage of viral infections determine the quality and magnitude of immune responses against the invading virus. The release of membrane-encapsulated extracellular vesicles (EVs), from host cells, is defined as a refined system of cell-to-cell communication. EVs contain a diverse array of biomolecules, including microRNAs (miRNAs). We hypothesized that the activation of the tracheal cells with different stimuli impacts the cellular and EV miRNA profiles. Chicken tracheal rings were stimulated with polyI:C and LPS from Escherichia coli 026:B6 or infected with low pathogenic avian influenza virus H4N6. Subsequently, miRNAs were isolated from chicken tracheal cells or from EVs released from chicken tracheal cells. Differentially expressed (DE) miRNAs were identified in treated groups when compared to the control group. Our results demonstrated that there were 67 up-regulated miRNAs, 157 down-regulated miRNAs across all cellular and EV samples. In the next step, several genes or pathways targeted by DE miRNAs were predicted. Overall, this study presented a global miRNA expression profile in chicken tracheas in response to avian influenza viruses (AIV) and toll-like receptor (TLR) ligands. The results presented predicted the possible roles of some DE miRNAs in the induction of antiviral responses. The DE candidate miRNAs, including miR-146a, miR-146b, miR-205a, miR-205b and miR-449, can be investigated further for functional validation studies and to be used as novel prophylactic and therapeutic targets in tailoring or enhancing antiviral responses against AIV.

scholarly journals The lung–gut axis during viral respiratory infections: the impact of gut dysbiosis on secondary disease outcomes

2021 ◽  
Author(s):  
Valentin Sencio ◽  
Marina Gomes Machado ◽  
François Trottein
Keyword(s):  
Gut Microbiota ◽  
Bacterial Infections ◽  
Respiratory Infections ◽  
Critical Role ◽  
Good Health ◽  
Disease Outcomes ◽  
And Function ◽  
Viral Respiratory Infections ◽  
The Impact ◽  
Viral Respiratory

AbstractBacteria that colonize the human gastrointestinal tract are essential for good health. The gut microbiota has a critical role in pulmonary immunity and host’s defense against viral respiratory infections. The gut microbiota’s composition and function can be profoundly affected in many disease settings, including acute infections, and these changes can aggravate the severity of the disease. Here, we discuss mechanisms by which the gut microbiota arms the lung to control viral respiratory infections. We summarize the impact of viral respiratory infections on the gut microbiota and discuss the potential mechanisms leading to alterations of gut microbiota’s composition and functions. We also discuss the effects of gut microbial imbalance on disease outcomes, including gastrointestinal disorders and secondary bacterial infections. Lastly, we discuss the potential role of the lung–gut axis in coronavirus disease 2019.

scholarly journals Low pathogenic avian influenza virus infection retards colon microbiome diversification in two different chicken lines

2021 ◽  
Author(s):  
Klaudia Chrzastek ◽  
Joy Leng ◽  
Mohammad Khalid Zakaria ◽  
Dagmara Bialy ◽  
Roberto LaRagione ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Avian Influenza ◽  
Avian Influenza Virus ◽  
Rhode Island ◽  
Post Infection ◽  
Influenza Infection ◽  
Influenza Virus Infection ◽  
Virus Infectivity ◽  
The Impact

A commensal microbiome regulates and is in turn regulated by viruses during host infection which can influence virus infectivity. In this study, analysis of colon microbiome population changes following a low pathogenicity avian influenza virus (AIV) of the H9N2 subtype infection of two different chicken breeds was conducted. Using 16S rRNA sequencing and subsequent data analysis we found reduced microbiome alpha diversity in the acute period of AIV infection (day 2-3) in both Rhode Island Red and VALO chicken lines. From day 4 post infection a gradual increase in diversity of the colon microbiome was observed, but the diversity did not reach the same level as in uninfected chickens by day 10 post infection, suggesting that AIV infection retards the natural accumulation of colon microbiome diversity, which may further influence chicken health following recovery from infection. Beta diversity analysis indicated differences in diversity between the chicken lines during and following acute influenza infection suggesting the impact of host gut microflora dysbiosis following H9N2 influenza virus infection could differ for different breeds.

scholarly journals Enisamium Reduces Influenza Virus Shedding and Improves Patient Recovery by Inhibiting Viral RNA Polymerase Activity

2021 ◽  
Vol 65 (4) ◽  
Author(s):  
Aartjan J. W. te Velthuis ◽  
Tatiana G. Zubkova ◽  
Megan Shaw ◽  
Andrew Mehle ◽  
David Boltz ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Placebo Group ◽  
Rna Polymerase ◽  
Rna Synthesis ◽  
Respiratory Infections ◽  
Respiratory Viruses ◽  
Virus Shedding ◽  
Virus Rna ◽  
Viral Respiratory Infections ◽  
Viral Respiratory

ABSTRACT Infections with respiratory viruses constitute a huge burden on our health and economy. Antivirals against some respiratory viruses are available, but further options are urgently needed. Enisamium iodide (laboratory code FAV00A, trade name Amizon) is an antiviral, marketed in countries of the Commonwealth of Independent States for the treatment of viral respiratory infections, but its clinical efficacy and mode of action are not well understood. In this study, we investigated the efficacy of enisamium in patients aged between 18 and 60 years with confirmed influenza virus and other viral respiratory infections. Enisamium treatment resulted in reduced influenza virus shedding (at day 3, 71.2% in the enisamium group tested negative versus 25.0% in placebo group [P < 0.0001]), faster patient recovery (at day 14, 93.9% in the enisamium group had recovered versus 32.5% in placebo group [P < 0.0001]), and reduced disease symptoms (from 9.6 ± 0.7 to 4.6 ± 0.9 score points in enisamium group versus 9.7 ± 1.1 to 5.6 ± 1.1 score points in placebo group [P < 0.0001]) compared to those in the placebo group. Using mass spectrometry, and cell-based and cell-free viral RNA synthesis assays, we identified a hydroxylated metabolite of enisamium, VR17-04. VR17-04 is capable of inhibiting influenza virus RNA synthesis and is present in plasma of patients treated with enisamium. VR17-04 inhibits the activity of the influenza virus RNA polymerase more potently than its parent compound. Overall, these results suggest that enisamium is metabolized in humans to an inhibitor of the influenza virus RNA polymerase that reduces viral shedding and improves patient recovery in influenza patients. (This study has been registered at ClinicalTrials.gov under identifier NCT04682444.)

scholarly journals The Impact of Migratory Flyways on the Spread of Avian Influenza Virus in North America

2016 ◽  
Author(s):  
Mathieu Fourment ◽  
Aaron E. Darling ◽  
Edward C. Holmes
Keyword(s):  
Influenza Virus ◽  
Genetic Structure ◽  
North America ◽  
Avian Influenza ◽  
Avian Influenza Virus ◽  
Bird Species ◽  
Influenza Viruses ◽  
Data Sets ◽  
Avian Influenza Viruses ◽  
The Impact

AbstractWild birds are the major reservoir hosts for influenza A viruses (AIVs) and have been implicated in the emergence of pandemic events in livestock and human populations. Understanding how AIVs spread within and across continents is therefore critical to the development of successful strategies to manage and reduce the impact of influenza outbreaks. In North America many bird species undergo seasonal migratory movements along a North-South axis, thereby fostering opportunities for viruses to spread over long distances. However, the role played by such avian flyways in shaping the genetic structure of AIV populations has proven controversial. To assess the relative contribution of bird migration along flyways to the genetic structure of AIV we performed a large-scale phylogeographic study of viruses sampled in the USA and Canada, involving the analysis of 3805 to 4505 sequences from 36 to 38 geographic localities depending on the gene data set. To assist this we developed a maximum likelihood-based genetic algorithm to explore a wide range of complex spatial models, thereby depicting a more complete picture of the migration network than previous studies. Based on phylogenies estimated from nucleotide data sets, our results show that AIV migration rates within flyways are significantly higher than those between flyways, indicating that the migratory patterns of birds play a key role in pathogen dispersal. These findings provide valuable insights into the evolution, maintenance and transmission of AIVs, in turn allowing the development of improved programs for surveillance and risk assessment.Significance StatementAvian influenza viruses infect a wide variety of wild bird species and represent a potential disease threat to the poultry industry and hence to human and livestock populations. However, the ecological factors that drive the geographic spread and evolution of these viruses are both poorly understood and controversial at the continental scale, particularly the role played by migratory flyways in shaping patterns of virus dispersal. Using a novel phylogeographic analysis of large genomic data sets we show migration flyways act as important transmission barriers to the spread of avian influenza viruses in North America. Hence, these results indicate that the spread of avian influenza virus in wild birds in North America has an element of predictability.

scholarly journals A Review of the Role Micronutrient Status in the Elderly Plays in Their Immune Response to Viral Respiratory Infections and the Potential Compromising Effects Medications Might Cause

2020 ◽  
pp. 59-85
Author(s):  
Michael P. Wakeman
Keyword(s):  
Immune System ◽  
Respiratory Infections ◽  
The Elderly ◽  
Micronutrient Status ◽  
Viral Respiratory Infections ◽  
The Impact ◽  
Global Population ◽  
Healthy Immune System ◽  
Viral Respiratory

The elderly are a growing proportion of the global population. They are more susceptible to non-communicable diseases and respiratory viral diseases like influenza and covid19, which may lead to increased levels of morbidity and mortality than those of a younger generation. It is also reported that co-morbidities, especially diabetes, hypertension and coronary heart disease contribute significantly to the prognosis with these types of infections. That the immune system operates in a less efficient way as an individual ages, is now well understood and likely contributes significantly to this situation. The role of certain micronutrients in maintaining a healthy immune system is well recognised and demonstrated to play an important role both in preventing and controlling infection. However, for a number of reasons many elderly individuals have a less than optimal intake of many of the micronutrients that support the immune system. This review examines the contributory roles an aging immune system, suboptimal intake of micronutrients, comorbidities and the impact of the intake of medications typically used to treat them can play in the outcome of viral respiratory infections. It identifies the need for supplementation, especially in the elderly to support the immune system.

scholarly journals Adaptive amino acid substitutions enable transmission of an H9N2 avian influenza virus in guinea pigs

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Liu Lina ◽  
Chen Saijuan ◽  
Wang Chengyu ◽  
Lu Yuefeng ◽  
Dong Shishan ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Hong Kong ◽  
Amino Acid ◽  
Avian Influenza ◽  
Avian Influenza Virus ◽  
Reverse Genetics ◽  
Amino Acid Substitutions ◽  
Potential Threat ◽  
Pathogenic Avian Influenza Virus ◽  
The Impact

AbstractH9N2 is the most prevalent low pathogenic avian influenza virus (LPAIV) in domestic poultry in the world. Two distinct H9N2 poultry lineages, G1-like (A/quail/Hong Kong/G1/97) and Y280-like (A/Duck/Hong Kong/Y280/1997) viruses, are usually associated with binding affinity for both α 2,3 and α 2,6 sialic acid receptors (avian and human receptors), raising concern whether these viruses possess pandemic potential. To explore the impact of mouse adaptation on the transmissibility of a Y280-like virus A/Chicken/Hubei/214/2017(H9N2) (abbreviated as WT), we performed serial lung-to-lung passages of the WT virus in mice. The mouse-adapted variant (MA) exhibited enhanced pathogenicity and advantaged transmissibility after passaging in mice. Sequence analysis of the complete genomes of the MA virus revealed a total of 16 amino acid substitutions. These mutations distributed across 7 segments including PB2, PB1, PA, NP, HA, NA and NS1 genes. Furthermore, we generated a panel of recombinant or mutant H9N2 viruses using reverse genetics technology and confirmed that the PB2 gene governing the increased pathogenicity and transmissibility. The combinations of 340 K and 588 V in PB2 were important in determining the altered features. Our findings elucidate the specific mutations in PB2 contribute to the phenotype differences and emphasize the importance of monitoring the identified amino acid substitutions due to their potential threat to human health.

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