scholarly journals Oral Supplementation of the Vitamin D Metabolite 25(OH)D3 Against Influenza Virus Infection in Mice

Nutrients ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 2000
Author(s):  
Hirotaka Hayashi ◽  
Masatoshi Okamatsu ◽  
Honami Ogasawara ◽  
Naoko Tsugawa ◽  
Norikazu Isoda ◽  
...  
Keyword(s):  
Vitamin D ◽  
Influenza Virus ◽  
Virus Infection ◽  
Inflammatory Cytokines ◽  
Influenza A ◽  
Clinical Manifestations ◽  
Influenza Virus Infection ◽  
High Dose ◽  
Oral Supplementation ◽  
Hydroxyvitamin D

Vitamin D is a fat-soluble vitamin that is metabolized by the liver into 25-hydroxyvitamin D [25(OH)D] and then by the kidney into 1,25-dihydroxyvitamin D [1,25(OH)2D], which activates the vitamin D receptor expressed in various cells, including immune cells, for an overall immunostimulatory effect. Here, to investigate whether oral supplementation of 25-hydroxyvitamin D3 [25(OH)D3], a major form of vitamin D metabolite 25(OH)D, has a prophylactic effect on influenza A virus infection, mice were fed a diet containing a high dose of 25(OH)D3 and were challenged with the influenza virus. In the lungs of 25(OH)D3-fed mice, the viral titers were significantly lower than in the lungs of standardly fed mice. Additionally, the proinflammatory cytokines IL-5 and IFN-γ were significantly downregulated after viral infection in 25(OH)D3-fed mice, while anti-inflammatory cytokines were not significantly upregulated. These results indicate that 25(OH)D3 suppresses the production of inflammatory cytokines and reduces virus replication and clinical manifestations of influenza virus infection in a mouse model.

Impact of influenza virus during pregnancy: from disease severity to vaccine efficacy

2020 ◽  
Vol 15 (7) ◽  
pp. 441-453
Author(s):  
Ana Vazquez-Pagan ◽  
Rebekah Honce ◽  
Stacey Schultz-Cherry
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Immune Responses ◽  
Pregnant Women ◽  
Disease Severity ◽  
Influenza A ◽  
Antiviral Treatment ◽  
Influenza Virus Infection ◽  
Severe Influenza ◽  
The Impact

Pregnant women are among the individuals at the highest risk for severe influenza virus infection. Infection of the mother during pregnancy increases the probability of adverse fetal outcomes such as small for gestational age, preterm birth and fetal death. Animal models of syngeneic and allogeneic mating can recapitulate the increased disease severity observed in pregnant women and are used to define the mechanism(s) of that increased severity. This review focuses on influenza A virus pathogenesis, the unique immunological landscape during pregnancy, the impact of maternal influenza virus infection on the fetus and the immune responses at the maternal–fetal interface. Finally, we summarize the importance of immunization and antiviral treatment in this population and highlight issues that warrant further investigation.

A Fungal Cu/Zn-Containing Superoxide Dismutase Enhances the Therapeutic Efficacy of a Plant Polyphenol Extract in Experimental Influenza Virus Infection

2010 ◽  
Vol 65 (5-6) ◽  
pp. 419-428 ◽  
Author(s):  
Julia Serkedjieva ◽  
Tsvetanka Stefanova ◽  
Ekaterina Krumova
Keyword(s):  
Superoxide Dismutase ◽  
Influenza Virus ◽  
Virus Infection ◽  
Protective Effect ◽  
Influenza A ◽  
Influenza Virus Infection ◽  
Protective Role ◽  
Combined Application ◽  
Combined Use ◽  
Experimental Influenza

The combined protective effect of a polyphenol-rich extract, isolated from Geranium sanguineum L. (PC), and a novel naturally glycosylated Cu/Zn-containing superoxide dismutase, produced from the fungal strain Humicula lutea 103 (HL-SOD), in the experimental influenza A virus infection (EIVI) in mice, induced with the virus A/Aichi/2/68 (H3N2), was investigated. The combined application of HL-SOD and PC in doses, which by themselves do not defend significantly mice in EIVI, resulted in a synergistically increased protection, determined on the basis of protective indices and amelioration of lung injury. Lung weights and consolidation as well as infectious lung virus titers were all decreased significantly parallel to the reduction of the mortality rates; lung indices were raised. The excessive production of reactive oxygen species (ROS) by alveolar macrophages (aMØ) as well as the elevated levels of the lung antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), induced by EIVI, were brought to normal. For comparative reasons the combined protective effect of PC and vitamin C was investigated. The obtained results support the combined use of antioxidants for the treatment of influenza virus infection and in general indicate the beneficial protective role of combinations of viral inhibitors of natural origin with diverse modes of action.

Severe Influenza Virus Infection in Children Admitted to the PICU: Comparison of Influenza A and Influenza B Virus Infection

2021 ◽  
Author(s):  
Pınar YAZICI ÖZKAYA ◽  
Eşe Eda TURANLI ◽  
Hamdi METİN ◽  
Ayça Aydın UYSAL ◽  
Candan ÇİÇEK ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Influenza A ◽  
Influenza Virus Infection ◽  
Influenza B Virus ◽  
Influenza B ◽  
Severe Influenza ◽  
B Virus

scholarly journals IFITM3 protects the heart during influenza virus infection

2019 ◽  
Author(s):  
Adam D. Kenney ◽  
Temet M. McMichael ◽  
Alexander Imas ◽  
Nicholas M. Chesarino ◽  
Lizhi Zhang ◽  
...  
Keyword(s):  
Heart Rate ◽  
Influenza Virus ◽  
Virus Infection ◽  
Cardiac Dysfunction ◽  
Influenza A ◽  
Transmembrane Protein ◽  
Influenza Virus Infection ◽  
Small Animal ◽  
Heart Tissue ◽  
Underlying Mechanisms

AbstractInfluenza virus primarily targets the lungs, but dissemination and damage to heart tissue is also known to occur in severe infections. Despite this knowledge, influenza virus-induced cardiac pathogenesis and its underlying mechanisms have been difficult to study due to a lack of small animal models. In humans, polymorphisms in the gene encoding interferon-induced transmembrane protein 3 (IFITM3), an antiviral restriction factor, are associated with susceptibility to severe influenza, but whether IFITM3 deficiencies contribute to other aspects of pathogenesis, including cardiac dysfunction, is unknown. We now show that IFITM3 deficiency in a newly generated knockout (KO) mouse model exacerbates illness and mortality following influenza A virus infection. Enhanced pathogenesis correlated with increased replication of virus in the lungs, spleens, and hearts of KO mice relative to wildtype (WT) mice. IFITM3 KO mice exhibited normal cardiac function at baseline, but developed severely aberrant electrical activity upon infection, including decreased heart rate and irregular, arrhythmic RR (interbeat) intervals. In contrast, WT mice exhibited a mild decrease in heart rate without irregularity of RR intervals. Heightened cardiac virus titers and electrical dysfunction in KO animals was accompanied by increased activation of fibrotic pathways and fibrotic lesions in the heart. Our findings reveal an essential role for IFITM3 in controlling influenza virus replication and pathogenesis in heart tissue and establish IFITM3 KO mice as a powerful model to study virus-induced cardiac dysfunction.

scholarly journals Routine blood parameters are helpful for early identification of influenza infection in children

2020 ◽  
Author(s):  
Ronghe Zhu ◽  
Cuie Chen ◽  
Qiu Wang ◽  
Xixi Zhang ◽  
Chaosheng Lu ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Influenza A Virus ◽  
Early Identification ◽  
Influenza A ◽  
Influenza Infection ◽  
Influenza Virus Infection ◽  
Cutoff Value ◽  
Routine Blood ◽  
Influenza A Virus Infection

Abstract Purpose Routine blood parameters, such as the lymphocyte (LYM) count, platelet (PLT) count, lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), LYM*PLT and mean platelet volume-to-platelet ratio (MPV/PLT), are widely used to predict the prognosis of infectious diseases. We aimed to explore the value of these parameters in the early identification of influenza virus infection in children.Methods We conducted a single-center, retrospective, observational study of fever with influenza-like symptoms in pediatric outpatients from different age groups and evaluated the predictive value of various routine blood parameters measured within 48 hours of the onset of fever for influenza virus infection.Results The LYM count, PLT count, LMR and LYM*PLT were lower, and the NLR and MPV/PLT were higher in children with an influenza infection (PCR-confirmed and symptomatic). The LYM count, LMR and LYM*PLT in the influenza infection group were lower in the 1- to 6-year-old subgroup, and the LMR and LYM*PLT in the influenza infection group were lower in the >6-year-old subgroup. In the 1- to 6-year-old subgroup, the cutoff value of the LMR for predicting influenza A virus infection was 3.75, the sensitivity was 81.87%, the specificity was 84.31%, and the area under the curve (AUC) was 0.886; the cutoff value of the LMR for predicting influenza B virus infection was 3.71, the sensitivity was 73.58%, the specificity was 84.31%, and the AUC was 0.843. In the >6-year-old subgroup, the cutoff value of the LMR for predicting influenza A virus infection was 3.05, the sensitivity was 89.27%, the specificity was 89.61%, and the AUC was 0.949; the cutoff value of the LMR for predicting influenza B virus infection was 2.88, the sensitivity was 83.19%, the specificity was 92.21%, and the AUC was 0.924.Conclusions Routine blood tests are simple, inexpensive and easy to perform, and they are useful for the early identification of influenza virus infection in children. The LMR had the strongest predictive value for influenza virus infection in children older than 1 year, particularly influenza A virus infection.

scholarly journals Serum High-Mobility-Group Box 1 as a Biomarker and a Therapeutic Target during Respiratory Virus Infections

mBio ◽  
2018 ◽  
Vol 9 (2) ◽  
Author(s):  
Mira C. Patel ◽  
Kari Ann Shirey ◽  
Marina S. Boukhvalova ◽  
Stefanie N. Vogel ◽  
Jorge C. G. Blanco
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Influenza A ◽  
Influenza Virus Infection ◽  
High Mobility ◽  
Influenza B Virus ◽  
Influenza B ◽  
Lung Pathology ◽  
B Virus ◽  
Cotton Rats

ABSTRACT Host-derived “danger-associated molecular patterns” (DAMPs) contribute to innate immune responses and serve as markers of disease progression and severity for inflammatory and infectious diseases. There is accumulating evidence that generation of DAMPs such as oxidized phospholipids and high-mobility-group box 1 (HMGB1) during influenza virus infection leads to acute lung injury (ALI). Treatment of influenza virus-infected mice and cotton rats with the Toll-like receptor 4 (TLR4) antagonist Eritoran blocked DAMP accumulation and ameliorated influenza virus-induced ALI. However, changes in systemic HMGB1 kinetics during the course of influenza virus infection in animal models and humans have yet to establish an association of HMGB1 release with influenza virus infection. To this end, we used the cotton rat model that is permissive to nonadapted strains of influenza A and B viruses, respiratory syncytial virus (RSV), and human rhinoviruses (HRVs). Serum HMGB1 levels were measured by an enzyme-linked immunosorbent assay (ELISA) prior to infection until day 14 or 18 post-infection. Infection with either influenza A or B virus resulted in a robust increase in serum HMGB1 levels that decreased by days 14 to 18. Inoculation with the live attenuated vaccine FluMist resulted in HMGB1 levels that were significantly lower than those with infection with live influenza viruses. RSV and HRVs showed profiles of serum HMGB1 induction that were consistent with their replication and degree of lung pathology in cotton rats. We further showed that therapeutic treatment with Eritoran of cotton rats infected with influenza B virus significantly blunted serum HMGB1 levels and improved lung pathology, without inhibiting virus replication. These findings support the use of drugs that block HMGB1 to combat influenza virus-induced ALI. IMPORTANCE Influenza virus is a common infectious agent causing serious seasonal epidemics, and there is urgent need to develop an alternative treatment modality for influenza virus infection. Recently, host-derived DAMPs, such as oxidized phospholipids and HMGB1, were shown to be generated during influenza virus infection and cause ALI. To establish a clear link between influenza virus infection and HMGB1 as a biomarker, we have systematically analyzed temporal patterns of serum HMGB1 release in cotton rats infected with nonadapted strains of influenza A and B viruses and compared these patterns with a live attenuated influenza vaccine and infection by other respiratory viruses. Towards development of a new therapeutic modality, we show herein that blocking serum HMGB1 levels by Eritoran improves lung pathology in influenza B virus-infected cotton rats. Our study is the first report of systemic HMGB1 as a potential biomarker of severity in respiratory virus infections and confirms that drugs that block virus-induced HMGB1 ameliorate ALI.

Combined Effect of Influenza Virus Infection and Urethan Treatment on the Incidence of Lung: Tumors in Mice.

1965 ◽  
Vol 51 (6) ◽  
pp. 401-417 ◽  
Author(s):  
Anna Maria Casazza ◽  
Marcello Gaetani ◽  
Mario Ghione ◽  
Enrico Turolla
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Joint Action ◽  
Influenza A ◽  
Influenza Virus Infection ◽  
Alveolar Epithelium ◽  
Bronchial Epithelium ◽  
Lung Tumors ◽  
Pulmonary Tissue ◽  
Two Agents

Swiss mice were intranasally infected with influenza A2 virus and treated with urethan in order to detect whether the joint action of the two agents would enhance the development of lung tumors. The average number per mouse of the typical lesions induced by the two treatments together with their location, their histological and histochemical characteristics and the percentage of death in the different groups of animals were recorded. Results indicated that 51.7 % of the mice infected with influenza virus and treated with urethan had both bronchial dysplastic lesions due to influenza virus, and tumors induced by urethan. In this group the number of tumors was smaller than in the mice treated with the carcinogen only and no invasive pulmonary carcinomas were observed. The dysplastic lesions caused by influenza A2 virus as well as the lung adenomas induced by urethan maintained their typical histological and histochemical characteristics even when occurring in a close position. The failure of urethan to enhance the induction of lung tumors in mice exposed to influenzal infection might be ascribed to the different primary sites of response of the pulmonary tissue to the two agents, i.e. the bronchial epithelium for influenza virus and the alveolar epithelium for urethan.

scholarly journals Phase III Randomized, Double-Blind Study Comparing Single-Dose Intravenous Peramivir with Oral Oseltamivir in Patients with Seasonal Influenza Virus Infection

2011 ◽  
Vol 55 (11) ◽  
pp. 5267-5276 ◽  
Author(s):  
Shigeru Kohno ◽  
Muh-Yong Yen ◽  
Hee-Jin Cheong ◽  
Nobuo Hirotsu ◽  
Tadashi Ishida ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Influenza A ◽  
Seasonal Influenza ◽  
Influenza Virus Infection ◽  
Influenza Viruses ◽  
Phase Iii ◽  
Controlled Study ◽  
Double Blind Study ◽  
Double Blind

ABSTRACTAntiviral medications with activity against influenza viruses are important in controlling influenza. We compared intravenous peramivir, a potent neuraminidase inhibitor, with oseltamivir in patients with seasonal influenza virus infection. In a multinational, multicenter, double-blind, double-dummy randomized controlled study, patients aged ≥20 years with influenza A or B virus infection were randomly assigned to receive either a single intravenous infusion of peramivir (300 or 600 mg) or oral administration of oseltamivir (75 mg twice a day [b.i.d.] for 5 days). To demonstrate the noninferiority of peramivir in reducing the time to alleviation of influenza symptoms with hazard model analysis and a noninferiority margin of 0.170, we planned to recruit 1,050 patients in South Korea, Japan, and Taiwan. A total of 1,091 patients (364 receiving 300 mg and 362 receiving 600 mg of peramivir; 365 receiving oseltamivir) were included in the intent-to-treat infected population. The median durations of influenza symptoms were 78.0, 81.0, and 81.8 h in the groups treated with 300 mg of peramivir, 600 mg of peramivir, and oseltamivir, respectively. The hazard ratios of the 300- and 600-mg-peramivir groups compared to the oseltamivir group were 0.946 (97.5% confidence interval [CI], 0.793, 1.129) and 0.970 (97.5% CI, 0.814, 1.157), respectively. Both peramivir groups were noninferior to the oseltamivir group (97.5% CI, <1.170). The overall incidence of adverse drug reactions was significantly lower in the 300-mg-peramivir group, but the incidence of severe reactions in either peramivir group was not different from that in the oseltamivir group. Thus, a single intravenous dose of peramivir may be an alternative to a 5-day oral dose of oseltamivir for patients with seasonal influenza virus infection.

scholarly journals Protective effect of low-concentration chlorine dioxide gas against influenza A virus infection

2008 ◽  
Vol 89 (1) ◽  
pp. 60-67 ◽  
Author(s):  
Norio Ogata ◽  
Takashi Shibata
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Influenza A Virus ◽  
Chlorine Dioxide ◽  
Influenza A ◽  
Influenza Virus Infection ◽  
Envelope Proteins ◽  
Viral Envelope ◽  
Exposure Level ◽  
Low Concentration

Influenza virus infection is one of the major causes of human morbidity and mortality. Between humans, this virus spreads mostly via aerosols excreted from the respiratory system. Current means of prevention of influenza virus infection are not entirely satisfactory because of their limited efficacy. Safe and effective preventive measures against pandemic influenza are greatly needed. We demonstrate that infection of mice induced by aerosols of influenza A virus was prevented by chlorine dioxide (ClO2) gas at an extremely low concentration (below the long-term permissible exposure level to humans, namely 0.1 p.p.m.). Mice in semi-closed cages were exposed to aerosols of influenza A virus (1 LD50) and ClO2 gas (0.03 p.p.m.) simultaneously for 15 min. Three days after exposure, pulmonary virus titre (TCID50) was 102.6±1.5 in five mice treated with ClO2, whilst it was 106.7±0.2 in five mice that had not been treated (P=0.003). Cumulative mortality after 16 days was 0/10 mice treated with ClO2 and 7/10 mice that had not been treated (P=0.002). In in vitro experiments, ClO2 denatured viral envelope proteins (haemagglutinin and neuraminidase) that are indispensable for infectivity of the virus, and abolished infectivity. Taken together, we conclude that ClO2 gas is effective at preventing aerosol-induced influenza virus infection in mice by denaturing viral envelope proteins at a concentration well below the permissible exposure level to humans. ClO2 gas could therefore be useful as a preventive means against influenza in places of human activity without necessitating evacuation.

scholarly journals Influenza Virus Infection Induces Metallothionein Gene Expression in the Mouse Liver and Lung by Overlapping but Distinct Molecular Mechanisms

2001 ◽  
Vol 21 (24) ◽  
pp. 8301-8317 ◽  
Author(s):  
Kalpana Ghoshal ◽  
Sarmila Majumder ◽  
Qin Zhu ◽  
John Hunzeker ◽  
Jharna Datta ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Glucocorticoid Receptor ◽  
Influenza A ◽  
Molecular Mechanisms ◽  
Influenza Virus Infection ◽  
Upper Respiratory Tract ◽  
Response Element ◽  
Induction Process ◽  
Ifn Γ

ABSTRACT Metallothionein I (MT-I) and MT-II have been implicated in the protection of cells against reactive oxygen species (ROS), heavy metals, and a variety of pathological and environmental stressors. Here, we show a robust increase in MT-I/MT-II mRNA level and MT proteins in the livers and lungs of C57BL/6 mice exposed to the influenza A/PR8 virus that infects the upper respiratory tract and lungs. Interleukin-6 (IL-6) had a pronounced effect on the induction of these genes in the liver but not the lung. Treatment of the animals with RU-486, a glucocorticoid receptor antagonist, inhibited induction of MT-I/MT-II in both liver and lung, revealing a direct role of glucocorticoid that is increased upon infection in this induction process. In vivo genomic footprinting (IVGF) analysis demonstrated involvement of almost all metal response elements, major late transcription factor/antioxidant response element (MLTF/ARE), the STAT3 binding site on the MT-I upstream promoter, and the glucocorticoid responsive element (GRE1), located upstream of the MT-II gene, in the induction process in the liver and lung. In the lung, inducible footprinting was also identified at a unique gamma interferon (IFN-γ) response element (γ-IRE) and at Sp1 sites. The mobility shift analysis showed activation of STAT3 and the glucocorticoid receptor in the liver and lung nuclear extracts, which was consistent with the IVGF data. Analysis of the newly synthesized mRNA for cytokines in the infected lung by real-time PCR showed a robust increase in the levels of IL-10 and IFN-γ mRNA that can activate STAT3 and STAT1, respectively. A STAT1-containing complex that binds to the γ-IRE in vitro was activated in the infected lung. No major change in MLTF/ARE DNA binding activity in the liver and lung occurred after infection. These results have demonstrated that MT-I and MT-II can be induced robustly in the liver and lung following experimental influenza virus infection by overlapping but distinct molecular mechanisms.

Sign in / Sign up

Export Citation Format

Share Document