scholarly journals Kinetics Of Interferon-λ And Receptor Expression In Response To In Vitro Respiratory Viral Infection

2021 ◽  
Author(s):  
Alexey Lozhkov ◽  
Nikita Yolshin ◽  
Irina Baranovskaya ◽  
Marina Plotnikova ◽  
Mariia Sergeeva ◽  
...  
Keyword(s):  
Influenza A ◽  
Alveolar Epithelial Cell ◽  
Mrna Level ◽  
Receptor Expression ◽  
Influenza B Virus ◽  
Influenza B ◽  
Type I ◽  
Viral Spread ◽  
Syncytial Virus

The major protective immune response against viruses is production of type I and III interferons (IFNs). IFNs induce the expression of hundreds of IFN-stimulated genes (ISGs) that block viral replication and further viral spread. The ability of respiratory viruses to suppress induction of IFN-mediated antiviral defenses in infected epithelial cells may be a factor contributing to the particular pathogenicity of several strains. In this report, we analyzed expression of IFNs and some ISGs in an alveolar epithelial cell subtype (A549) in response to infection with: influenza A viruses (A/California/07/09pdm (H1N1), A/Texas/50/12 (H3N2)); influenza B virus (B/Phuket/3073/13); adenovirus type 5 and 6; or respiratory syncytial virus (strain A2). IFNL and ISGs expression significantly increased in response to infection with all RNA viruses 24 hpi. Nevertheless, only IBV led to early increase in IFNL and ISGs mRNA level. IBV and H1N1 infection led to elevated proinflammatory cytokine production. We speculate that augmented IFN-α, IFN-β, IL-6 levels negatively correlate to SOCS1 expression. Importantly, we showed a decrease in IFNLR1 mRNA in case of IBV infection that implies the existence of negative ISGs expression regulation at IFNλR level. It could be either a specific feature of IBV or a consequence of early IFNL expression.

scholarly journals TMPRSS2 Is the Major Activating Protease of Influenza A Virus in Primary Human Airway Cells and Influenza B Virus in Human Type II Pneumocytes

2019 ◽  
Vol 93 (21) ◽  
Author(s):  
Hannah Limburg ◽  
Anne Harbig ◽  
Dorothea Bestle ◽  
David A. Stein ◽  
Hong M. Moulton ◽  
...  
Keyword(s):  
Influenza A ◽  
Influenza B Virus ◽  
Influenza B ◽  
Virus Infectivity ◽  
Type Ii ◽  
Proteolytic Activation ◽  
Human Airway ◽  
Type Ii Pneumocytes ◽  
Airway Cells

ABSTRACT Cleavage of influenza virus hemagglutinin (HA) by host cell proteases is essential for virus infectivity and spread. We previously demonstrated in vitro that the transmembrane protease TMPRSS2 cleaves influenza A virus (IAV) and influenza B virus (IBV) HA possessing a monobasic cleavage site. Subsequent studies revealed that TMPRSS2 is crucial for the activation and pathogenesis of H1N1pdm and H7N9 IAV in mice. In contrast, activation of H3N2 IAV and IBV was found to be independent of TMPRSS2 expression and supported by an as-yet-undetermined protease(s). Here, we investigated the role of TMPRSS2 in proteolytic activation of IAV and IBV in three human airway cell culture systems: primary human bronchial epithelial cells (HBEC), primary type II alveolar epithelial cells (AECII), and Calu-3 cells. Knockdown of TMPRSS2 expression was performed using a previously described antisense peptide-conjugated phosphorodiamidate morpholino oligomer, T-ex5, that interferes with splicing of TMPRSS2 pre-mRNA, resulting in the expression of enzymatically inactive TMPRSS2. T-ex5 treatment produced efficient knockdown of active TMPRSS2 in all three airway cell culture models and prevented proteolytic activation and multiplication of H7N9 IAV in Calu-3 cells and H1N1pdm, H7N9, and H3N2 IAV in HBEC and AECII. T-ex5 treatment also inhibited the activation and spread of IBV in AECII but did not affect IBV activation in HBEC and Calu-3 cells. This study identifies TMPRSS2 as the major HA-activating protease of IAV in human airway cells and IBV in type II pneumocytes and as a potential target for the development of novel drugs to treat influenza infections. IMPORTANCE Influenza A viruses (IAV) and influenza B viruses (IBV) cause significant morbidity and mortality during seasonal outbreaks. Cleavage of the viral surface glycoprotein hemagglutinin (HA) by host proteases is a prerequisite for membrane fusion and essential for virus infectivity. Inhibition of relevant proteases provides a promising therapeutic approach that may avoid the development of drug resistance. HA of most influenza viruses is cleaved at a monobasic cleavage site, and a number of proteases have been shown to cleave HA in vitro. This study demonstrates that the transmembrane protease TMPRSS2 is the major HA-activating protease of IAV in primary human bronchial cells and of both IAV and IBV in primary human type II pneumocytes. It further reveals that human and murine airway cells can differ in their HA-cleaving protease repertoires. Our data will help drive the development of potent and selective protease inhibitors as novel drugs for influenza treatment.

scholarly journals Influenza B Virus NS1-Truncated Mutants: Live-Attenuated Vaccine Approach

2008 ◽  
Vol 82 (21) ◽  
pp. 10580-10590 ◽  
Author(s):  
Rong Hai ◽  
Luis Martínez-Sobrido ◽  
Kathryn A. Fraser ◽  
Juan Ayllon ◽  
Adolfo García-Sastre ◽  
...  
Keyword(s):  
Reverse Genetics ◽  
Influenza Viruses ◽  
Influenza B Virus ◽  
Influenza B ◽  
Type I ◽  
Live Attenuated Vaccine ◽  
Live Virus ◽  
B Virus

ABSTRACT Type B influenza viruses can cause substantial morbidity and mortality in the population, and vaccination remains by far the best means of protection against infections with these viruses. Here, we report the construction of mutant influenza B viruses for potential use as improved live-virus vaccine candidates. Employing reverse genetics, we altered the NS1 gene, which encodes a type I interferon (IFN) antagonist. The resulting NS1 mutant viruses induced IFN and, as a consequence, were found to be attenuated in vitro and in vivo. The absence of pathogenicity of the NS1 mutants in both BALB/c and C57BL/6 PKR−/− mice was confirmed. We also provide evidence that influenza B virus NS1 mutants induce a self-adjuvanted immune response and confer effective protection against challenge with both homologous and heterologous B virus strains in mice.

scholarly journals The Panther Fusion System with Open Access Functionality for Laboratory-Developed Tests for Influenza A Virus Subtyping

2020 ◽  
Vol 58 (6) ◽  
Author(s):  
Kathleen A. Stellrecht ◽  
Jesse L. Cimino ◽  
Vincente P. Maceira
Keyword(s):  
Open Access ◽  
Influenza A ◽  
Limit Of Detection ◽  
Turnaround Time ◽  
Nucleic Acid Amplification ◽  
Influenza B ◽  
Fusion System ◽  
Valuable Complement ◽  
Syncytial Virus

ABSTRACT Nucleic acid amplification tests, such as PCR, are the method of choice for respiratory virus testing, due to their superior diagnostic accuracy and fast turnaround time. The Panther Fusion (Fusion; Hologic) system has an array of highly sensitive in vitro diagnostic (IVD) real-time PCR assays for respiratory viruses, including an assay for influenza A (FluA) virus, influenza B (FluB) virus, and respiratory syncytial virus (RSV) (FFABR assay). The Fusion system has Open Access functionality to perform laboratory-developed tests (LDTs) alongside IVD assays. We developed two LDTs for FluA virus strain typing on the Panther Fusion instrument, enabling side-by-side testing with the FFABR assay. The LDT-FAST assay uses proprietary primers and probes designed by Hologic for the Prodesse ProFAST+ (PFAST) assay. The exWHO-FAST assay is an expanded redesign of the WHO-recommended reverse transcriptase PCRs (RT-PCRs). To evaluate the performance of these two LDTs, 110 FluA virus-positive samples were tested. Of these, 104 had been subtyped previously; 54 were H3, 46 were 09H1, and 4 were fsH1. All were appropriately subtyped by both LDTs. Of the untyped FluA virus samples, three were subtyped as H3 by both LDTs and two were subtyped as H3 by the LDT-FAST assay only. The sample not subtyped by either LDT was retested with the FFABR assay and was now negative. Limit-of-detection (LOD) analyses were performed with five FluA virus strains. The LDT-FAST LODs were similar to the FFABR assay LODs, while the exWHO-FAST LODs were higher for two H3N2 strains, findings that were explained by analysis of primer/probe homology. In conclusion, either FluA virus typing assay would be a valuable complement to the Panther Fusion respiratory menu given the performance of these LDTs, the system’s full automation, and the ability to split eluates for both IVD and LDT testing.

scholarly journals A comparison of influenza and respiratory syncytial virus infections among infants admitted to hospital with acute respiratory infections

1976 ◽  
Vol 77 (3) ◽  
pp. 383-392 ◽  
Author(s):  
E. O. Caul ◽  
D. K. Waller ◽  
S. K. R. Clarke ◽  
B. D. Corner
Keyword(s):  
Influenza Virus ◽  
Respiratory Syncytial Virus ◽  
Rural Areas ◽  
Influenza A ◽  
Respiratory Infections ◽  
Influenza B Virus ◽  
Influenza B ◽  
Virus Infections ◽  
Syncytial Virus ◽  
One Year

SUMMARYAmong 741 children under 5 years admitted to hospital with respiratory infections during two winters, infection with influenza A virus was diagnosed in 70 (9%), with influenza B virus in 8 (1%), and with respiratory syncytial virus (RSV) in 259 (35 %). Both influenza virus and RSV infections were diagnosed most frequently in children under the age of one year, and diagnosed more frequently in males than females. Influenza illnesses were more severe in boys than girls. Both infections occurred more often, but were not more severe, in children from a conurbation than in those from ‘rural’ areas. Convulsions were the cause of 36% of admissions with influenza A infections, but were rare in RSV infections. Bronchiolitis was the reason for 39% of admissions with RSV infections, but was rare in influenza infections. It is suggested that infants admitted to hospital are a good source of influenza virus strains for monitoring arttigenic variation.

scholarly journals Performance of a Novel Point-of-Care Molecular Assay for Detection of Influenza A and B Viruses and Respiratory Syncytial Virus (Enigma MiniLab) in Children with Acute Respiratory Infection

2015 ◽  
Vol 54 (1) ◽  
pp. 212-215 ◽  
Author(s):  
Sam T. Douthwaite ◽  
Charlotte Walker ◽  
Elisabeth J. Adams ◽  
Catherine Mak ◽  
Andres Vecino Ortiz ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Influenza A ◽  
Respiratory Virus ◽  
Point Of Care ◽  
Influenza B Virus ◽  
Influenza B ◽  
Molecular Assay ◽  
B Virus ◽  
Syncytial Virus ◽  
Virus Influenza

The performance of the Enigma MiniLab assay for influenza A and B viruses and respiratory syncytial virus (RSV) was compared to a centralized laboratory respiratory virus panel. The positive and negative percent agreement for influenza A virus, influenza B virus, and RSV were 79.2% (95% confidence interval [95% CI], 57.8 to 92.9%) and 99.4% (95% CI, 98.4 to 99.9), 100% (95% CI, 47.8 to 100%) and 100% (95% CI, 99.3 to 100%), 98.5% (95% CI, 94.6 to 99.8%) and 94.5% (95% CI, 91.9 to 96.4%), respectively.

scholarly journals Transmission of Acute Respiratory Infections in a City: Agent-Based Approach

2020 ◽  
Vol 15 (2) ◽  
pp. 338-356
Author(s):  
A.I. Vlad ◽  
T.E. Sannikova ◽  
A.A. Romanyukha
Keyword(s):  
Incidence Rate ◽  
Influenza A ◽  
Respiratory Infections ◽  
Reproductive Rate ◽  
Immune Memory ◽  
Influenza B Virus ◽  
Influenza B ◽  
Acute Respiratory Infections ◽  
Agent Based ◽  
Syncytial Virus

An incidence curve of acute respiratory infections in Moscow has three picks between September and April and reaches its maximum in January- February. The emergence of new strains of influenza A could account for only one pick a year. The most cases of common cold are caused by ubiquitous low pathogenic viruses. In order to simulate weekly fluctuation of incidence rate of acute respiratory illnesses we developed an agent-based model. It contains 10 millions agents with such attributes as sex, age, social status, levels of specific immune memory and lists of contacts. Each agent can contact with members of its household, colleagues or classmates. Through such contacts susceptible agent can be infected with one of seven circulating respiratory viruses. Viruses differ in their immunologic properties and assume to present influenza A virus, influenza B virus, parainfluenza, adenovirus, coronavirus, rhinovirus and respiratory syncytial virus. The rate of transmission depends on duration of contact, vulnerability of susceptible agent, infectivity of infected agent and air temperature. Proposed network of social interactions proved to be sufficiently detailed as it provided good fitting for observed incidence rate including periods of school holidays and winter public holidays. Additionally, the estimates of basic reproductive rate for the viruses confirm that all these viruses except new strains of influenza A are relatively harmless and unable to cause significant growth of acute respiratory infections morbidity.

scholarly journals Evaluation of Performance Characteristics of Panther Fusion Assays for Detection of Respiratory Viruses from Nasopharyngeal and Lower Respiratory Tract Specimens

2018 ◽  
Vol 56 (8) ◽  
Author(s):  
Soya S. Sam ◽  
Angela M. Caliendo ◽  
Jessica Ingersoll ◽  
Deborah Abdul-Ali ◽  
Charles E. Hill ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Positive Result ◽  
Lower Respiratory Tract ◽  
Influenza A ◽  
Performance Characteristics ◽  
Influenza B Virus ◽  
Influenza B ◽  
Respiratory Pathogens ◽  
Percent Agreement ◽  
Syncytial Virus

ABSTRACT Accurate and rapid diagnosis is needed for timely intervention and clinical management of acute respiratory infections. This study evaluated performance characteristics of the Panther Fusion assay for the detection of influenza A virus (Flu A), influenza B virus (Flu B), respiratory syncytial virus (RSV), parainfluenza viruses 1 to 3 (Para 1 to 3), human metapneumovirus (hMPV), rhinovirus (RV), and adenovirus (Adeno) targets in comparison to those of the eSensor and Lyra assays using 395 nasopharyngeal (NP) and 104 lower respiratory tract (LRT) specimens. Based on the consensus positive result established (positive result in 2 of the 3 assays), the NP specimens for the Fusion and eSensor assays had 100% positive percent agreement (PPA) for all the analytes and the Lyra assays had 100% PPA for Flu A and Adeno analytes. A 100% negative percent agreement (NPA) was observed for all the Lyra analytes, whereas those for the Fusion targets ranged from 98.4 to 100% and those for the eSensor ranged from 99.4 to 100% for all the analytes except RV. For the LRT specimens, Fusion had 100% PPA and 100% NPA for all the targets except hMPV. There was a 100% PPA for eSensor analytes; the NPA ranged from 98 to 100%, except for RV. For the Lyra assays, the PPA ranged between 50 and 100%, while the NPA was 100% for all the targets except Adeno. The Fusion assay performed similarly to the eSensor assay for majority of the targets tested and provides laboratories with a fully automated random-access system to test for a broad array of viral respiratory pathogens.

In vitro evaluation of the antiviral effects of the homeopathic preparation Gripp-Heel on selected respiratory virusesThis article is one of a selection of papers published in this special issue (part 2 of 2) on the Safety and Efficacy of Natural Health Products.

2007 ◽  
Vol 85 (11) ◽  
pp. 1084-1090 ◽  
Author(s):  
Bernadette Glatthaar-Saalmüller
Keyword(s):  
Antiviral Activity ◽  
Influenza A ◽  
Human Herpesvirus ◽  
Mononuclear Leukocytes ◽  
Type I ◽  
Natural Health Products ◽  
Peripheral Blood Mononuclear ◽  
Syncytial Virus ◽  
Homeopathic Preparation

Gripp-Heel® is a homeopathic preparation frequently used in the treatment of respiratory viral infections such as various types of influenza and the common cold. The antiviral activity of Gripp-Heel was studied in vitro on human pathogenic enveloped and nonenveloped RNA and DNA viruses. Before the antiviral assays, in vitro cytotoxicity of Gripp-Heel was determined with cells used for the infection experiments (HeLa, HEp-2, MDCK, BGM) as well as with mitogen-stimulated peripheral blood mononuclear leukocytes. A concentration of 0.5 of the commercially available product slightly reduced cell viability and proliferative capacity, and experiments on antiviral activity were determined starting with a dilution of 0.2 of the commercially available product. The antiviral activity was determined against a broad panel of enveloped and nonenveloped DNA and RNA viruses with plaque reduction assay, cytopathogenic assays, virus titrations, analysis of the viral proteins in virus-specific enzyme immunoassays, and haemagglutination tests. Control substances were acyclovir (10 μg/mL), ribavirin (6 μg/mL), and amantadine hydrochloride (5 μg/mL), depending on the virus type. Gripp-Heel demonstrated dose-dependent in vitro activity (significant reductions of infectivity by 20% to 40%) against Human herpesvirus 1, Human adenovirus C serotype 5, Influenza A virus, Human respiratory syncytial virus, Human parainfluenza virus 3, Human rhinovirus B serotype 14, and Human coxsackievirus serotype A9. The mechanisms of this antiviral activity are still unclear, but type I interferon induction might be a possible explanation. Further research on this homeopathic preparation seems warranted.

scholarly journals A Reverse Genetics Approach for Recovery of Recombinant Influenza B Viruses Entirely from cDNA

2002 ◽  
Vol 76 (22) ◽  
pp. 11744-11747 ◽  
Author(s):  
David Jackson ◽  
Andrew Cadman ◽  
Thomas Zurcher ◽  
Wendy S. Barclay
Keyword(s):  
Amino Acid ◽  
Influenza A ◽  
Amino Acid Change ◽  
Reverse Genetics ◽  
Single Gene ◽  
Neuraminidase Inhibitor ◽  
Influenza B Virus ◽  
Influenza B ◽  
B Virus

ABSTRACT The recovery of recombinant influenza A virus entirely from cDNA was recently described (9, 19). We adapted the technique for engineering influenza B virus and generated a mutant bearing an amino acid change E116G in the viral neuraminidase which was resistant in vitro to the neuraminidase inhibitor zanamivir. The method also facilitates rapid isolation of single-gene reassortants suitable as vaccine seeds and will aid further investigations of unique features of influenza B virus.

scholarly journals Defective interfering influenza A virus protects in vivo against disease caused by a heterologous influenza B virus

2011 ◽  
Vol 92 (9) ◽  
pp. 2122-2132 ◽  
Author(s):  
Paul D. Scott ◽  
Bo Meng ◽  
Anthony C. Marriott ◽  
Andrew J. Easton ◽  
Nigel J. Dimmock
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Influenza Viruses ◽  
Influenza B Virus ◽  
Influenza B ◽  
Type I ◽  
Type I Ifn ◽  
B Virus ◽  
The Family

Influenza A and B viruses are major human respiratory pathogens that contribute to the burden of seasonal influenza. They are both members of the family Orthomyxoviridae but do not interact genetically and are classified in different genera. Defective interfering (DI) influenza viruses have a major deletion of one or more of their eight genome segments, which renders them both non-infectious and able to interfere in cell culture with the production of infectious progeny by a genetically compatible, homologous virus. It has been shown previously that intranasal administration of a cloned DI influenza A virus, 244/PR8, protects mice from various homologous influenza A virus subtypes and that it also protects mice from respiratory disease caused by a heterologous virus belonging to the family Paramyxoviridae. The mechanisms of action in vivo differ, with homologous and heterologous protection being mediated by probable genome competition and type I interferon (IFN), respectively. In the current study, it was shown that 244/PR8 also protects against disease caused by a heterologous influenza B virus (B/Lee/40). Protection from B/Lee/40 challenge was partially eliminated in mice that did not express a functional type I IFN receptor, suggesting that innate immunity, and type I IFN in particular, are important in mediating protection against this virus. It was concluded that 244/PR8 has the ability to protect in vivo against heterologous IFN-sensitive respiratory viruses, in addition to homologous influenza A viruses, and that it acts by fundamentally different mechanisms.

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