scholarly journals Maoto, a Traditional Japanese Herbal Medicine, Inhibits Uncoating of Influenza Virus

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Shinta Masui ◽  
Shigeki Nabeshima ◽  
Kazuhiko Ajisaka ◽  
Kei Yamauchi ◽  
Ryota Itoh ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Herbal Medicine ◽  
A549 Cells ◽  
Virus Titer ◽  
Influenza Viruses ◽  
Viral Rna ◽  
Virus Particles ◽  
Endosomal Acidification ◽  
Infected Cells ◽  
Virological Efficacy

We previously reported in randomized controlled trials that maoto, a traditional herbal medicine, showed clinical and virological efficacy for seasonal influenza. In this study, a culturing system for influenza was used to test the effect of maoto. A549 cells in the culture were infected with influenza virus A (PR8) and followed after treatment with maoto; the virus titers in the culture supernatant, intracellular viral proteins, and viral RNA were determined. When infected cells were cultured with maoto for 24 hr, the virus titer and protein were significantly reduced compared with medium only. Other subtypes, A/H3N2, H1N1pdm, and B, were also inhibited by maoto. Proliferation of viral RNA in a 6 hr culture was inhibited by maoto in the early phase, especially in the first 30 min. Focusing on the entry step of the influenza virus, we found that endosomal pH, regulated by vacuolar-type H+ATPase (V-ATPase) located in the membrane, was increased when treated with maoto. We also found that uncoating of influenza viruses was also inhibited by maoto, resulting in the increase of the number of virus particles in endosomes. These results strongly suggest that the inhibition of endosomal acidification by maoto results in blocking influenza virus entry to cytoplasm, probably through the inhibition of V-ATPase. The present study provides evidence that supports the clinical use of maoto for the treatment of influenza.

scholarly journals Involvement of Hsp90 in Assembly and Nuclear Import of Influenza Virus RNA Polymerase Subunits

2006 ◽  
Vol 81 (3) ◽  
pp. 1339-1349 ◽  
Author(s):  
Tadasuke Naito ◽  
Fumitaka Momose ◽  
Atsushi Kawaguchi ◽  
Kyosuke Nagata
Keyword(s):  
Influenza Virus ◽  
Rna Polymerase ◽  
Nuclear Transport ◽  
Intracellular Localization ◽  
Viral Rna ◽  
Polymerase Complex ◽  
Virus Rna ◽  
Binary Complexes ◽  
Infected Cells ◽  
Rna Polymerase Subunits

ABSTRACT Transcription and replication of the influenza virus RNA genome occur in the nuclei of infected cells through the viral RNA-dependent RNA polymerase consisting of PB1, PB2, and PA. We previously identified a host factor designated RAF-1 (RNA polymerase activating factor 1) that stimulates viral RNA synthesis. RAF-1 is found to be identical to Hsp90. Here, we examined the intracellular localization of Hsp90 and viral RNA polymerase subunits and their molecular interaction. Hsp90 was found to interact with PB2 and PB1, and it was relocalized to the nucleus upon viral infection. We found that the nuclear transport of Hsp90 occurs in cells expressing PB2 alone. The nuclear transport of Hsp90 was in parallel with that of the viral RNA polymerase binary complexes, either PB1 and PB2 or PB1 and PA, as well as with that of PB2 alone. Hsp90 also interacted with the binary RNA polymerase complex PB1-PB2, and it was dissociated from the PB1-PB2 complex upon its association with PA. Furthermore, Hsp90 could form a stable PB1-PB2-Hsp90 complex prior to the formation of a ternary polymerase complex by the assembly of PA in the infected cells. These results suggest that Hsp90 is involved in the assembly and nuclear transport of viral RNA polymerase subunits, possibly as a molecular chaperone for the polymerase subunits prior to the formation of a mature ternary polymerase complex.

scholarly journals Antibody to influenza virus matrix protein detects a common antigen on the surface of cells infected with type A influenza viruses.

1977 ◽  
Vol 146 (3) ◽  
pp. 690-697 ◽  
Author(s):  
W E Biddison ◽  
P C Doherty ◽  
R G Webster
Keyword(s):  
Influenza Virus ◽  
Matrix Protein ◽  
Type A ◽  
Cross Reactivity ◽  
T Cell Response ◽  
Influenza Viruses ◽  
Cytotoxic T Cell ◽  
Target Cells ◽  
Common Antigen ◽  
Infected Cells

Antisera to the type-specific internal influenza virus matrix (M) protein of a type A influenza virus were produced in goats. In the presence of complement, anti-M serum was cytotoxic for target cells which were infected with a variety of serologically distinct type A influenza viruses, but did not react with type B influenza virus-infected cells. Absorption experiments indicated that anti-M serum detected a common antigen(s) on the surface of type A-infected cells. This serological cross-reactivity parallels the cross-reactivity observed for the cytotoxic T-cell response to type A viruses.

scholarly journals Antiviral Activity and Underlying Action Mechanism of Euglena Extract against Influenza Virus

Nutrients ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 3911
Author(s):  
Ayaka Nakashima ◽  
Yuka Horio ◽  
Kengo Suzuki ◽  
Yuji Isegawa
Keyword(s):  
Influenza Virus ◽  
Antiviral Activity ◽  
Defense Mechanisms ◽  
Mdck Cells ◽  
Influenza Virus Infection ◽  
Virus Titer ◽  
Prolonged Treatment ◽  
Action Mechanism ◽  
Cell Defense ◽  
Infected Cells

It is difficult to match annual vaccines against the exact influenza strain that is spreading in any given flu season. Owing to the emergence of drug-resistant viral strains, new approaches for treating influenza are needed. Euglena gracilis (hereinafter Euglena), microalga, used as functional foods and supplements, have been shown to alleviate symptoms of influenza virus infection in mice. However, the mechanism underlying the inhibitory action of microalgae against the influenza virus is unknown. Here, we aimed to study the antiviral activity of Euglena extract against the influenza virus and the underlying action mechanism using Madin–Darby canine kidney (MDCK) cells. Euglena extract strongly inhibited infection by all influenza virus strains examined, including those resistant to the anti-influenza drugs oseltamivir and amantadine. A time-of-addition assay revealed that Euglena extract did not affect the cycle of virus replication, and cell pretreatment or prolonged treatment of infected cells reduced the virus titer. Thus, Euglena extract may activate the host cell defense mechanisms, rather than directly acting on the influenza virus. Moreover, various minerals, mainly zinc, in Euglena extract were found to be involved in the antiviral activity of the extract. In conclusion, Euglena extract could be a potent agent for preventing and treating influenza.

scholarly journals Antiviral Activity of Chrysin against Influenza Virus Replication via Inhibition of Autophagy

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1350
Author(s):  
Seong-Ryeol Kim ◽  
Myeong-Seon Jeong ◽  
Seo-Hyeon Mun ◽  
Jaewon Cho ◽  
Min-Duk Seo ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Influenza A ◽  
Time Course ◽  
Respiratory Infections ◽  
A549 Cells ◽  
Enterovirus 71 ◽  
Influenza Viruses ◽  
High Morbidity ◽  
Early Stages ◽  
Infected Cells

Influenza viruses cause respiratory infections in humans and animals, which have high morbidity and mortality rates. Although several drugs that inhibit viral neuraminidase are used to treat influenza infections, the emergence of resistant viruses necessitates the urgent development of new antiviral drugs. Chrysin (5,7-dihydroxyflavone) is a natural flavonoid that exhibits antiviral activity against enterovirus 71 (EV71) by inhibiting viral 3C protease activity. In this study, we evaluated the antiviral activity of chrysin against influenza A/Puerto Rico/8/34 (A/PR/8). Chrysin significantly inhibited A/PR/8-mediated cell death and the replication of A/PR/8 at concentrations up to 2 mM. Viral hemagglutinin expression was also markedly decreased by the chrysin treatment in A/PR/8-infected cells. Through the time course experiment and time-of-addition assay, we found that chrysin inhibited viral infection at the early stages of the replication cycle. Additionally, the nucleoprotein expression of A/PR/8 in A549 cells was reduced upon treatment with chrysin. Regarding the mechanism of action, we found that chrysin inhibited autophagy activation by increasing the phosphorylation of mammalian target of rapamycin (mTOR). We also confirmed a decrease in LC3B expression and LC3-positive puncta levels in A/PR/8-infected cells. These results suggest that chrysin exhibits antiviral activity by activating mTOR and inhibiting autophagy to inhibit the replication of A/PR/8 in the early stages of infection.

scholarly journals MicroRNAs affect GPCR and Ion channel genes needed for influenza replication

2021 ◽  
Vol 102 (11) ◽  
Author(s):  
Nichole Orr-Burks ◽  
Jackelyn Murray ◽  
Kyle V. Todd ◽  
Abhijeet Bakre ◽  
Ralph A. Tripp
Keyword(s):  
Influenza Virus ◽  
Ion Channel ◽  
Virus Replication ◽  
Target Genes ◽  
A549 Cells ◽  
Influenza Viruses ◽  
Economic Losses ◽  
Alveolar Epithelial ◽  
Influenza Virus Replication ◽  
Host Genes

Influenza virus causes seasonal epidemics and sporadic pandemics resulting in morbidity, mortality, and economic losses worldwide. Understanding how to regulate influenza virus replication is important for developing vaccine and therapeutic strategies. Identifying microRNAs (miRs) that affect host genes used by influenza virus for replication can support an antiviral strategy. In this study, G-protein coupled receptor (GPCR) and ion channel (IC) host genes in human alveolar epithelial (A549) cells used by influenza virus for replication (Orr-Burks et al., 2021) were examined as miR target genes following A/CA/04/09- or B/Yamagata/16/1988 replication. Thirty-three miRs were predicted to target GPCR or IC genes and their miR mimics were evaluated for their ability to decrease influenza virus replication. Paired miR inhibitors were used as an ancillary measure to confirm or not the antiviral effects of a miR mimic. Fifteen miRs lowered influenza virus replication and four miRs were found to reduce replication irrespective of virus strain and type differences. These findings provide evidence for novel miR disease intervention strategies for influenza viruses.

Palmitoylation of influenza virus proteins

2013 ◽  
Vol 41 (1) ◽  
pp. 50-55 ◽  
Author(s):  
Michael Veit ◽  
Marina V. Serebryakova ◽  
Larisa V. Kordyukova
Keyword(s):  
Influenza Viruses ◽  
Spike Protein ◽  
Proton Channel ◽  
Membrane Rafts ◽  
Target Cells ◽  
Virus Particles ◽  
Functional Consequences ◽  
Infected Cells ◽  
Fatty Acid Species ◽  
Acylated Proteins

Influenza viruses contain two palmitoylated (S-acylated) proteins: the major spike protein HA (haemagglutinin) and the proton-channel M2. The present review describes the fundamental biochemistry of palmitoylation of HA: the location of palmitoylation sites and the fatty acid species bound to HA. Finally, the functional consequences of palmitoylation of HA and M2 are discussed regarding association with membrane rafts, entry of viruses into target cells by HA-mediated membrane fusion as well as the release of newly assembled virus particles from infected cells.

scholarly journals DISRUPTION OF INFLUENZA VIRUS

1954 ◽  
Vol 99 (4) ◽  
pp. 321-342 ◽  
Author(s):  
David A. J. Tyrrell ◽  
Frank L. Horsfall
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Influenza Viruses ◽  
Influenza B ◽  
Infective Virus ◽  
Freezing And Thawing ◽  
Virus Particles ◽  
Homologous Virus ◽  
Repeated Freezing ◽  
Antigen Activity

1. The hemagglutinating capacity, enzymic activity, and infectivity of several influenza viruses were destroyed by repeated freezing and thawing of dialyzed allantoic fluids containing them. 2. Influenza virus degraded by freezing and thawing, by treatment with 5 M urea, or by heating at 65°C. still combined with homologous antibody and was demonstrable by blocking of the hemagglutination-inhibition and virus neutralization reactions. 3. After 50 cycles of freezing and thawing, much of the blocking antigen activity was not sedimented by centrifugation at 120,000 g for 2 hours, and electron microscopy showed complete disruption of the virus particles. So called soluble blocking antigen was obtained from four strains of influenza A, the Lee strain of influenza B, mumps, and Newcastle disease viruses. 4. Soluble blocking antigens from influenza A viruses were highly strain-specific; gave little or no reaction in complement-fixation tests; stimulated but little antibody production in rabbits and did not induce immunity in mice; caused reactivation of infective virus in neutral mixtures of homologous virus and immune serum. 5. Repeatedly frozen and thawed influenza virus preparations did not interfere with the propagation of infective virus in the allantoic sac. The blocking antigen activity they contained was precipitated by half saturated ammonium sulfate, destroyed by trypsin, chymotrypsin, or heating at 56°C. for 30 minutes, but was unaffected by desoxyribonuclease or ribonuclease. 6. These findings are in accord with the view that soluble blocking antigen obtained from influenza virus particles on disruption by repeated freezing and thawing is protein in nature and represents the essential antigenic material of the intact virus.

scholarly journals Ethanol Extract of Caesalpinia decapetala Inhibits Influenza Virus Infection In Vitro and In Vivo

Viruses ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 557 ◽  
Author(s):  
Li Zhang ◽  
Jungang Chen ◽  
Chang Ke ◽  
Haiwei Zhang ◽  
Shoujun Zhang ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Antiviral Agents ◽  
Influenza Virus Infection ◽  
Virus Titer ◽  
Ethanol Extract ◽  
Influenza Viruses ◽  
Virus Infections

Influenza virus infections can lead to viral pneumonia and acute respiratory distress syndrome in severe cases, causing significant morbidity and mortality and posing a great threat to human health. Because of the diversity of influenza virus strains and drug resistance to the current direct antiviral agents, there have been no effective drugs as yet to cure all patients infected by influenza viruses. Natural products from plants contain compounds with diverse structures that have the potential to interact with multiple host and virus factors. In this study, we identified the ethanol extract of Caesalpinia decapetala (Roth) Alston (EEC) as an inhibitor against the replication of a panel of influenza A and B viruses both on human pulmonary epithelial A549 and human monocytic U937 cells. The animal study revealed that EEC administration reduces the weight loss and improves the survival rate of mice infected with lethal influenza virus. Also, EEC treatment attenuated lung injury and reduced virus titer significantly. In conclusion, we showed that EEC has antiviral activity both in vitro and in vivo, suggesting that the plant C. decapetala has the potential to be further developed as a resource of new anti-influenza drugs.

scholarly journals Alterations in Receptor Binding Properties of Recent Human Influenza H3N2 Viruses Are Associated with Reduced Natural Killer Cell Lysis of Infected Cells

2007 ◽  
Vol 81 (20) ◽  
pp. 11170-11178 ◽  
Author(s):  
Rachel E. Owen ◽  
Eriko Yamada ◽  
Catherine I. Thompson ◽  
Louisa J. Phillipson ◽  
Clare Thompson ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Natural Killer ◽  
Nk Cell ◽  
Glycosylation Site ◽  
Influenza Viruses ◽  
Host Cells ◽  
Cell Recognition ◽  
Binding Properties ◽  
Infected Cells ◽  
H3n2 Influenza

ABSTRACT Natural killer (NK) cell recognition of influenza virus-infected cells involves hemagglutinin (HA) binding to sialic acid (SA) on activating NK receptors. SA also acts as a receptor for the binding of influenza virus to its target host cells. The SA binding properties of H3N2 influenza viruses have been observed to change during circulation in humans: recent isolates are unable to agglutinate chicken red blood cells and show reduced affinity for synthetic glycopolymers representing SA-α-2,3-lactose (3′SL-PAA) and SA-α-2,6-N-acetyl lactosamine (6′SLN-PAA) carbohydrates. Here, NK lysis of cells infected with human H3N2 influenza viruses isolated between 1969 and 2003 was analyzed. Cells infected with recent isolates (1999 to 2003) were found to be lysed less effectively than cells infected with older isolates (1969 to 1996). This change occurred concurrently with the acquisition of two new potential glycosylation site motifs in HA. Deletion of the potential glycosylation site motif at 133 to 135 in HA1 from a recent isolate partially restored the agglutination phenotype to a recombinant virus, indicating that the HA-SA interaction is inhibited by the glycosylation modification. Deletion of either of the recently acquired potential glycosylation sites from HA led to increased NK lysis of cells infected with recombinant viruses carrying modified HA. These results indicate that alterations in HA glycosylation may affect NK cell recognition of influenza virus-infected cells in addition to virus binding to host cells.

scholarly journals Human Staufen1 Protein Interacts with Influenza Virus Ribonucleoproteins and Is Required for Efficient Virus Multiplication

2010 ◽  
Vol 84 (15) ◽  
pp. 7603-7612 ◽  
Author(s):  
Susana de Lucas ◽  
Joan Peredo ◽  
Rosa María Marión ◽  
Carmen Sánchez ◽  
Juan Ortín
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Influenza A ◽  
Particle Production ◽  
Nonstructural Protein ◽  
A549 Cells ◽  
Influenza Virus Infection ◽  
Ns1 Protein ◽  
Infected Cells

ABSTRACT The influenza A virus genome consists of 8 negative-stranded RNA segments. NS1 is a nonstructural protein that participates in different steps of the virus infectious cycle, including transcription, replication, and morphogenesis, and acts as a virulence factor. Human Staufen1 (hStau1), a protein involved in the transport and regulated translation of cellular mRNAs, was previously identified as a NS1-interacting factor. To investigate the possible role of hStau1 in the influenza virus infection, we characterized the composition of hStau1-containing granules isolated from virus-infected cells. Viral NS1 protein and ribonucleoproteins (RNPs) were identified in these complexes by Western blotting, and viral mRNAs and viral RNAs (vRNAs) were detected by reverse transcription (RT)-PCR. Also, colocalization of hStau1 with NS1, nucleoprotein (NP), and PA in the cytosol of virus-infected cells was shown by immunofluorescence. To analyze the role of hStau1 in the infection, we downregulated its expression by gene silencing. Human HEK293T cells or A549 cells were silenced using either short hairpin RNAs (shRNAs) or small interfering RNAs (siRNAs) targeting four independent sites in the hStau1 mRNA. The yield of influenza virus was reduced 5 to 10 times in the various hStau1-silenced cells compared to that in control silenced cells. The expression levels of viral proteins and their nucleocytoplasmic localization were not affected upon hStau1 silencing, but virus particle production, as determined by purification of virions from supernatants, was reduced. These results indicate a role for hStau1 in late events of the influenza virus infection, possibly during virus morphogenesis.

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