IN VIVO TRANSCRIPTION AND TRANSLATION OF DEFECTIVE-INTERFERING PARTICLE-SPECIFIC RNAS OF INFLUENZA VIRUS

Author(s):  
Thomas M. Chambers ◽  
Ramesh K. Akkina ◽  
Debi P. Nayak
1980 ◽  
Vol 45 (5) ◽  
pp. 1595-1600 ◽  
Author(s):  
Jaroslav Sluka ◽  
František Šmejkal ◽  
Zdeněk Buděšínský

On recation of cyclooctylamine with the sulfate of S-methylisothiourea cyclooctylguanidine was formed which was acylated with the methyl esters of 5-halogeno- and 3,5-dihalogeno-2-alkoxybenzoic acids. The 1-acyl-3-cyclooctylguanidine I-XVII formed were tested for their antiviral effect against the influenza virus A/NWS, A-PR8 and A2 Singapore, and further against the viruses NDV, herpes 2, vaccinia and WEE. In the in vivo test against the influenza virus A2 Singapore and herpes simplex 1-(5-bromo-2-dodecyloxybenzoyl)-3-cyclooctylguanidine is more active and less toxic than cyclooctylamine and 1-cyclooctylguanidine.


1985 ◽  
Vol 162 (2) ◽  
pp. 663-674 ◽  
Author(s):  
A Yamada ◽  
M R Ziese ◽  
J F Young ◽  
Y K Yamada ◽  
F A Ennis

We have tested the abilities of various polypeptides of A/PR/8/34 (H1N1) virus, constructed by recombinant DNA techniques, to induce influenza virus-specific secondary cytotoxic T lymphocyte (CTL) responses. A hybrid protein (c13 protein), consisting of the first 81 amino acids of viral nonstructural protein (NS1) and the HA2 subunit of viral hemagglutinin (HA), induced H-2-restricted, influenza virus subtype-specific secondary CTL in vitro, although other peptides did not. Using a recombinant virus, the viral determinant responsible for recognition was mapped to the HA2 portion of c13 protein. Immunization of mice with c13 protein induced the generation of memory CTL in vivo. The CTL precursor frequencies of A/PR/8/34 virus- and c13 protein-immune mice were estimated as one in 8,047 and 50,312, respectively. These results indicate that c13 protein primed recipient mice, even though the level of precursor frequency was below that observed in virus-immune mice.


2003 ◽  
Vol 30 (6) ◽  
pp. 596-602
Author(s):  
I. N. Zhilinskaya ◽  
L. A. Lyapina ◽  
O. I. Kiselev ◽  
I. P. Ashmarin

2020 ◽  
Author(s):  
Ara Jo ◽  
Jina Won ◽  
Chan Hee Chil ◽  
Jae Young Choi ◽  
Kang-Mu Lee ◽  
...  

ABSTRACTOur recent study presented evidence that Staphylococcus epidermidis (S. epidermidis) was the most frequently encountered microbiome component in healthy human nasal mucus and that S. epidermidis could induce interferon (IFN)-dependent innate immunity to control acute viral lung infection. The serine protease inhibitor Serpine1 was identified to inhibit influenza A virus (IAV) spread by inhibiting glycoprotein cleavage, and the current study supports an additional mechanism of Serpine1 induction in the nasal mucosa, which can be regulated through S. epidermidis and IFN signaling. The exposure of in vivo mice to human S. epidermidis increased IFN-λ secretion in nasal mucosa and prevented an increase in the burden of IAV in the lung. S. epidermidis-inoculated mice exhibited the significant induction of Serpine1 in vivo in the nasal mucosa, and by targeting airway protease, S. epidermidis-induced Serpine1 inhibited the intracellular invasion of IAV to the nasal epithelium and led to restriction of IAV spreading to the lung. Furthermore, IFN-λ secretion was involved in the regulation of Serpine1 in S. epidermidis-inoculated nasal epithelial cells and in vivo nasal mucosa, and this was biologically relevant for the role of Serpine1 as an interferon-stimulated gene in the upper airway. Together, our findings reveal that human nasal commensal S. epidermidis manipulates the suppression of serine protease in in vivo nasal mucosa through Serpine1 induction and protects the nasal mucosa from IAV invasion through IFN-λ signaling.IMPORTANCEPreviously, we proved that nasal microbiome could enhance IFN-related innate immune responses to protect the respiratory tract against influenza virus infection. The present study shows a great understanding of the intimate association of S. epidermidis-regulated IFN-lambda induction and serine protease inhibitor in nasal mucosa. Our data demonstrate that S. epidermidis-regulated Serpine1 suppresses the invasion of influenza virus through suppression of airway serine protease at the level of nasal mucosa and impedes IAV spread to the respiratory tract. Thus, human nasal commensal S. epidermidis represents a therapeutic potential for treating respiratory viral infections via the change of cellular environment in respiratory tract.


2020 ◽  
Vol 2 (2) ◽  
pp. 43-48
Author(s):  
Valentina Divocha ◽  
◽  
Irina Komarevzeva ◽  

Introduction: Over the past 10 years, much attention has been paid to the development of new antiviral drugs based on the suppression of the proteolytic activity of enzymes by trypsin inhibitors of plant and animal origin. Material and methods: We used a trypsin inhibitor from barley, trielin- (isolated by employees of the Agro-Industrial Institute of Selection and Genetics of the Ukrainian Academy of Sciences from the salivary glands of a dog); ovomukoid (isolated from duck eggs by employees of N, I, Bach Research Institute of Biology, Russian Academy of Sciences); Influenza virus APR 8/34 (fourth passage), adapted to the lungs of mice at a dose of 20 LD /0.1 ml, titre HA( hemagglutenin) 1:32) ,white BALB/c mice weighing 12-14 g. Infection with influenza virus and treatment with inhibitors was carried out intranasally under light ether anesthesia. Doses studied were: 0.5mg/ml; 2.5 mg/ml; 5.0 mg/ml; The treatment regimen of 10 mg/ml differed only in the initial stages (1 hour before infection, during infection and 1 hour after infection, and then 6 hours after infection, 24 hours after infection, 48 hours after infection, 72 hours after infection and 96 hours after infection). Results and discussion: We found that an in vivo inhibitor from barley at a dose of 10 g/l delayed the development of influenza for 8 days. The ovomukoid possessed only prophylactic properties at a dose of 100 gamma / ml. With an increase in dose, it was toxic to animals. Trielin at a dose of 10 g/l had a pronounced therapeutic effect in influenza and was not toxic. The presence of hemagglutinin influenza virus in the lungs of treated mice was observed only on the 10th day after infection; 40% of the animals remained alive for 14 days (observation period).


2016 ◽  
Vol 113 (42) ◽  
pp. 11931-11936 ◽  
Author(s):  
Wenqian He ◽  
Gene S. Tan ◽  
Caitlin E. Mullarkey ◽  
Amanda J. Lee ◽  
Mannie Man Wai Lam ◽  
...  

The generation of strain-specific neutralizing antibodies against influenza A virus is known to confer potent protection against homologous infections. The majority of these antibodies bind to the hemagglutinin (HA) head domain and function by blocking the receptor binding site, preventing infection of host cells. Recently, elicitation of broadly neutralizing antibodies which target the conserved HA stalk domain has become a promising “universal” influenza virus vaccine strategy. The ability of these antibodies to elicit Fc-dependent effector functions has emerged as an important mechanism through which protection is achieved in vivo. However, the way in which Fc-dependent effector functions are regulated by polyclonal influenza virus-binding antibody mixtures in vivo has never been defined. Here, we demonstrate that interactions among viral glycoprotein-binding antibodies of varying specificities regulate the magnitude of antibody-dependent cell-mediated cytotoxicity induction. We show that the mechanism responsible for this phenotype relies upon competition for binding to HA on the surface of infected cells and virus particles. Nonneutralizing antibodies were poor inducers and did not inhibit antibody-dependent cell-mediated cytotoxicity. Interestingly, anti-neuraminidase antibodies weakly induced antibody-dependent cell-mediated cytotoxicity and enhanced induction in the presence of HA stalk-binding antibodies in an additive manner. Our data demonstrate that antibody specificity plays an important role in the regulation of ADCC, and that cross-talk among antibodies of varying specificities determines the magnitude of Fc receptor-mediated effector functions.


2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Christopher S. Anderson ◽  
Sandra Ortega ◽  
Francisco A. Chaves ◽  
Amelia M. Clark ◽  
Hongmei Yang ◽  
...  

Abstract The induction of antibodies specific for the influenza HA protein stalk domain is being pursued as a universal strategy against influenza virus infections. However, little work has been done looking at natural or induced antigenic variability in this domain and the effects on viral fitness. We analyzed human H1 HA head and stalk domain sequences and found substantial variability in both, although variability was highest in the head region. Furthermore, using human immune sera from pandemic A/California/04/2009 immune subjects and mAbs specific for the stalk domain, viruses were selected in vitro containing mutations in both domains that partially contributed to immune evasion. Recombinant viruses encoding amino acid changes in the HA stalk domain replicated well in vitro, and viruses incorporating two of the stalk mutations retained pathogenicity in vivo. These findings demonstrate that the HA protein stalk domain can undergo limited drift under immune pressure and the viruses can retain fitness and virulence in vivo, findings which are important to consider in the context of vaccination targeting this domain.


2010 ◽  
Vol 2010 ◽  
pp. 1-5 ◽  
Author(s):  
Laura V. Ashton ◽  
Robert L. Callan ◽  
Sangeeta Rao ◽  
Gabriele A. Landolt

Infection of dogs with canine influenza virus (CIV) is considered widespread throughout the United States following the first isolation of CIV in 2004. While vaccination against influenza A infection is a common and important practice for disease control, antiviral therapy can serve as a valuable adjunct in controlling the impact of the disease. In this study, we examined the antiviral activity of nitazoxanide (NTZ) and tizoxanide (TIZ) against three CIV isolatesin vitro. NTZ and TIZ inhibited virus replication of all CIVs with 50% and 90% inhibitory concentrations ranging from 0.17 to 0.21 μMand from 0.60 to 0.76 μM, respectively. These results suggest that NTZ and TIZ are effective against CIV and may be useful for treatment of canine influenza in dogs but further investigation of thein vivoefficacy against CIV as well as the drug's potential for toxicity in dogs is needed.


Biomaterials ◽  
2017 ◽  
Vol 138 ◽  
pp. 22-34 ◽  
Author(s):  
Sumati Bhatia ◽  
Daniel Lauster ◽  
Markus Bardua ◽  
Kai Ludwig ◽  
Stefano Angioletti-Uberti ◽  
...  

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