scholarly journals Antiviral Effects of Geranylgeranylacetone: Enhancement of MxA Expression and Phosphorylation of PKR during Influenza Virus Infection

2003 ◽  
Vol 47 (9) ◽  
pp. 2914-2921 ◽  
Author(s):  
Masako Unoshima ◽  
Hideo Iwasaka ◽  
Junko Eto ◽  
Yoshiko Takita-Sonoda ◽  
Takayuki Noguchi ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Antiviral Activity ◽  
Influenza Virus Infection ◽  
Antiviral Effect ◽  
Initiation Factor ◽  
Potent Inducer ◽  
Α Subunit

ABSTRACT A cyclic polyisoprenoid compound, geranylgeranylacetone (GGA), has been used as antiulcer drug. GGA is also a potent inducer of heat shock proteins (HSPs). HSPs are considered to induce an antiviral effect; however, the detailed mechanism is unknown. To determine whether GGA might show antiviral activity and what the mechanism is, the effect of GGA against influenza virus (strain PR8) infection in vivo and in vitro was investigated. The results demonstrated that GGA treatment strongly suppressed the deleterious consequences of PR8 replication and was accompanied by an increase in HSP70 gene expression in mice. Results from in vitro analyses demonstrated that GGA significantly inhibited the synthesis of PR8-associated proteins and prominently enhanced expression of human myxovirus resistance 1 (MxA) followed by increased HSP70 transcription. Moreover, GGA augmented the expression of an interferon-inducible double-strand RNA-activated protein kinase (PKR) gene and promoted PKR autophosphorylation and concomitantly α subunit of eukaryotic initiation factor 2 phosphorylation during PR8 infection. It is proposed that GGA-induced HSP70 has potent antiviral activity by enhancement of antiviral factors and can clinically achieve protection from influenza virus infection.

scholarly journals Linear polysialoside outperforms dendritic analogs for inhibition of influenza virus infection in vitro and in vivo

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

scholarly journals Oseltamivir-Ribavirin Combination Therapy for Highly Pathogenic H5N1 Influenza Virus Infection in Mice

2008 ◽  
Vol 52 (11) ◽  
pp. 3889-3897 ◽  
Author(s):  
Natalia A. Ilyushina ◽  
Alan Hay ◽  
Neziha Yilmaz ◽  
Adrianus C. M. Boon ◽  
Robert G. Webster ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza Virus Infection ◽  
Antiviral Effect ◽  
Influenza Viruses ◽  
Oseltamivir Carboxylate ◽  
Highly Pathogenic ◽  
H5n1 Influenza ◽  
Pathogenic H5n1

ABSTRACT We studied the effects of a neuraminidase inhibitor (oseltamivir) and an inhibitor of influenza virus polymerases (ribavirin) against two highly pathogenic H5N1 influenza viruses. In vitro, A/Vietnam/1203/04 virus (clade 1) was highly susceptible to oseltamivir carboxylate (50% inhibitory concentration [IC50] = 0.3 nM), whereas A/Turkey/15/06 virus (clade 2.2) had reduced susceptibility (IC50 = 5.5 nM). In vivo, BALB/c mice were treated with oseltamivir (1, 10, 50, or 100 mg/kg of body weight/day), ribavirin (37.5, 55, or 75 mg/kg/day), or the combination of both drugs for 8 days, starting 4 h before virus inoculation. Monotherapy produced a dose-dependent antiviral effect against the two H5N1 viruses in vivo. Three-dimensional analysis of the drug-drug interactions revealed that oseltamivir and ribavirin interacted principally in an additive manner, with several exceptions of marginal synergy or marginal antagonism at some concentrations. The combination of ribavirin at 37.5 mg/kg/day and oseltamivir at 1 mg/kg/day and the combination of ribavirin at 37.5 mg/kg/day and oseltamivir at 10 mg/kg/day were synergistic against A/Vietnam/1203/04 and A/Turkey/15/06 viruses, respectively. These optimal oseltamivir-ribavirin combinations significantly inhibited virus replication in mouse organs, prevented the spread of H5N1 viruses beyond the respiratory tract, and abrogated the cytokine response (P < 0.01). Importantly, we observed clear differences between the efficacies of the drug combinations against two H5N1 viruses: higher doses were required for the protection of mice against A/Turkey/15/06 virus than for the protection of mice against A/Vietnam/1203/04 virus. Our preliminary results suggest that oseltamivir-ribavirin combinations can have a greater or lesser antiviral effect than monotherapy, depending on the H5N1 virus and the concentrations used.

scholarly journals In Vitro and in Vivo Inhibitory Effects of Disodium Cromoglycate on Influenza Virus Infection

2004 ◽  
Vol 27 (6) ◽  
pp. 825-830 ◽  
Author(s):  
Kazuya I. P. J. Hidari ◽  
Eisaku Tsujii ◽  
Jun Hiroi ◽  
Eriko Mano ◽  
Akihiko Miyatake ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Influenza Virus Infection ◽  
Disodium Cromoglycate ◽  
Inhibitory Effects

scholarly journals Xanthophyll Accumulation Protects Mice from Influenza Virus Infection Potentially Through SirT3

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1528-1528
Author(s):  
Peiran Lu ◽  
Siau Yen Wong ◽  
Lei Wu ◽  
Mckale Montgomery ◽  
Winyoo Chowanadisai ◽  
...  
Keyword(s):  
Body Weight ◽  
Influenza Virus ◽  
Virus Infection ◽  
Knockout Mice ◽  
Influenza Virus Infection ◽  
Beta Carotene ◽  
Initiation Factor ◽  
Α Subunit ◽  
Mitochondrial Superoxide ◽  
Primary Mouse

Abstract Objectives Seasonal influenza virus infection is one of the top health concerns worldwide.  The beta-carotene oxygenase 2 (BCO2) knockout mice are more resistant to virus infection compared to wildtype. We sought to investigate the effects of xanthophylls, e.g., zeaxanthin (Z) and astaxanthin (A) in the regulation of the host innate immune responses to influenza A virus infection in mice. Methods Six-week-old male and female 129S6 wild type (WT), beta-carotene oxygenase 2 (BCO2) knockout mice, and BCO2/SIRT3 double knockout (DKO) mice were fed with AIN93M chow diets supplemented with or without Z (0.02% w/w) and A (0.02 w/w) (e.g., Z+A). After 5 weeks of the dietary intervention, mice were intranasally infected with 100 pfu H1N1 PR8 virus. Animal body weight and phenotypes were monitored daily. Animals were sacrificed 6 days post-infection. Blood and lung tissues were collected for experiments. H & E staining, ELISA, immunohistochemistry, and immunoblotting were used for clinical, histopathological, and other biochemical assessments. Further, primary mouse embryonic fibroblasts (MEF) cells were isolated from above three mouse strains. Mitochondrial superoxide was detected by MitoSOXTM live cell staining. Poly (I: C) was used to mimic virus infection in MEF cells. Results Much more significant body weight loss, lung damage, and cytokine storm occurred in WT and DKO mice after virus infection, as compared to the KO. Supplementation of Z+A significantly rescued the pathophenotypes in infected mice, particularly in KO mice. Basal mitochondrial superoxide levels were significantly higher in MEF cells of KO and DKO, compared to the MEF cells from WT mice.  The eukaryotic initiation factor 2 α-subunit level was significantly elevated in MEF cells of WT and DKO, after Poly (I: C) stimulation, compared to KO MEF cells. Application of Z at 0.625 μM significantly decreased mitochondrial superoxide levels in KO MEF cells. Conclusions BCO2 deficiency-associated xanthophyll accumulation protects animals and MEF cells from influenza virus pneumonia and mitochondrial superoxide production.  The effects are at least partially through Sirt3. Funding Sources This work was funded by grants from the Oklahoma Center for the Advancement of Science & Technology and the Oklahoma Agricultural Experiment Station.

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