scholarly journals Influenza Virus Infection Model With Density Dependence Supports Biphasic Viral Decay

2018 ◽  
Author(s):  
Amanda P. Smith ◽  
David J. Moquin ◽  
Veronika Bernhauerova ◽  
Amber M. Smith
Keyword(s):  
Viral Load ◽  
Kinetic Model ◽  
Influenza A ◽  
High Efficiency ◽  
Influenza Virus Infection ◽  
Infection Model ◽  
Viral Control ◽  
Viral Growth ◽  
New Model ◽  
Viral Kinetic

AbstractMathematical models that describe infection kinetics help elucidate the time scales, effectiveness, and mechanisms underlying viral growth and infection resolution. For influenza A virus (IAV) infections, the standard viral kinetic model has been used to investigate the effect of different IAV proteins, immune mechanisms, antiviral actions, and bacterial coinfection, among others. We sought to further define the kinetics of IAV infections by infecting mice with influenza A/PR8 and measuring viral loads with high frequency and precision over the course of infection. The data highlighted dynamics that were not previously noted, including viral titers that remain elevated for several days during mid-infection and a sharp 4-5 log10decline in virus within one day as the infection resolves. The standard viral kinetic model, which has been widely used within the field, could not capture these dynamics. Thus, we developed a new model that could simultaneously quantify the different phases of viral growth and decay with high accuracy. The model suggests that the slow and fast phases of virus decay are due to the infected cell clearance rate changing as the density of infected cells changes. To characterize this model, we fit the model to the viral load data, examined the parameter behavior, and connected the results and parameters to linear regression estimates. The resulting parameters and model dynamics revealed that the rate of viral clearance during resolution occurs 25 times faster than the clearance during mid-infection and that small decreases to this rate can significantly prolong the infection. This likely reflects the high efficiency of the adaptive immune response. The new model provides a well-characterized representation of IAV infection dynamics, is useful for analyzing and interpreting viral load dynamics in the absence of immunological data, and gives further insight into the regulation of viral control.

scholarly journals In Vitro System for Modeling Influenza A Virus Resistance under Drug Pressure

2010 ◽  
Vol 54 (8) ◽  
pp. 3442-3450 ◽  
Author(s):  
Ashley N. Brown ◽  
James J. McSharry ◽  
Qingmei Weng ◽  
Elizabeth M. Driebe ◽  
David M. Engelthaler ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A Virus ◽  
Virus Replication ◽  
Influenza A ◽  
Mdck Cells ◽  
Influenza Virus Infection ◽  
Infection Model ◽  
Virus Infections ◽  
Drug Pressure

ABSTRACT One of the biggest challenges in the effort to treat and contain influenza A virus infections is the emergence of resistance during treatment. It is well documented that resistance to amantadine arises rapidly during the course of treatment due to mutations in the gene coding for the M2 protein. To address this problem, it is critical to develop experimental systems that can accurately model the selection of resistance under drug pressure as seen in humans. We used the hollow-fiber infection model (HFIM) system to examine the effect of amantadine on the replication of influenza virus, A/Albany/1/98 (H3N2), grown in MDCK cells. At 24 and 48 h postinfection, virus replication was inhibited in a dose-dependent fashion. At 72 and 96 h postinfection, virus replication was no longer inhibited, suggesting the emergence of amantadine-resistant virus. Sequencing of the M2 gene revealed that mutations appeared at between 48 and 72 h of drug treatment and that the mutations were identical to those identified in the clinic for amantadine-resistant viruses (e.g., V27A, A30T, and S31N). Interestingly, we found that the type of mutation was strongly affected by the dose of the drug. The data suggest that the HFIM is a good model for influenza virus infection and resistance generation in humans. The HFIM has the advantage of being a highly controlled system where multiplicity parameters can be directly and accurately controlled and measured.

scholarly journals Tile: Combination Therapy of Zinc and Trimethoprim Inhibits Influenza A Virus In Chick Embryo

2021 ◽  
Author(s):  
Magdi El Habbal ◽  
Magdi H EL Habbal
Keyword(s):  
Influenza Virus ◽  
Viral Load ◽  
Chick Embryo ◽  
Influenza A Virus ◽  
Influenza A ◽  
Rna Viruses ◽  
Influenza Virus Infection ◽  
Lethal Effect ◽  
Embryo Survival ◽  
Optimal Ratio

Abstract Background. Respiratory RNA viruses including influenza virus have been a cause of health and economic hardships. These viruses depend on its host for replication and infection. Influenza virus infection is lethal to the chick embryo. We examined whether a combination of trimethoprim and zinc (Tri-Z), that acts on the host, can reduce the lethal effect of influenza A virus in chick embryo model. Method. Influenza virus was isolated from patients and propagated in eggs. We determined viral load that infects 50% of eggs (50% egg lethal dose, ELD50). We introduced 10 ELD50 into embryonated eggs and repeated the experiments using 100 ELD50. A mixture of zinc oxide (Zn) and trimethoprim (TMP) (weight / weight ratios ranged from 0.01 to 0.3, Zn/TMP with increment of 0.1) was tested for embryo survival of the infection (n = 12 per ratio, in triplicates). Embryo survival was determined by candling eggs daily for 7 days. Controls of Zn, TMP, saline or convalescent serum were conducted in parallel. The effect of Tri-Z on virus binding to its cell surface receptor was evaluated in a hemagglutination inhibition (HAI) assay using chicken red cells. Tri-Z was prepared to concentration of 10 mg TMP and 1.8 mg Zn per ml, then serial dilutions were made. HAI effect was expressed as scores where ++++ = no effect; 0 = complete HAI effect.Results. TMP, Zn or saline separately had no effect on embryo survival, none of the embryos survived influenza virus infection. All embryos treated with convalescent serum survived. Tri-Z, at ratio range of 0.15 to 0.2 (optimal ratio of 0.18) Zn / TMP, enabled embryos to survive influenza virus despite increasing viral load (>80% survival at optimal ratio). At concentration of 15 microgram/ml of optimal ratio, Tri-Z had total HAI effect (scored 0). However, at clinical concentration of 5 microgram/ml, Tri-Z had partial HAI effect (++).Conclusion. Acting on host cells, Tri-Z at optimal ratio can reduce the lethal effect of influenza A virus in chick embryo. Tri-Z has HAI effect. These findings suggest that combination of trimethoprim and zinc at optimal ratio can be provided as treatment for influenza and possibly other respiratory RNA viruses infection in man.

Combination Therapy of Zinc and Trimethoprim Inhibits Influenza A Virus in Chick Embryo  

2020 ◽  
Author(s):  
Magdi El Habbal ◽  
Magdi H EL Habbal
Keyword(s):  
Influenza Virus ◽  
Viral Load ◽  
Chick Embryo ◽  
Influenza A Virus ◽  
Influenza A ◽  
Rna Viruses ◽  
Influenza Virus Infection ◽  
Lethal Effect ◽  
Embryo Survival ◽  
Optimal Ratio

Abstract Background. Respiratory RNA viruses including influenza virus have been a cause of health and economic hardships. These viruses depend on its host for replication and infection. Influenza virus infection is lethal to the chick embryo. We examined whether a combination of trimethoprim and zinc (Tri-Z), that acts on the host, can reduce the lethal effect of influenza A virus in chick embryo model. Method. Influenza virus was isolated from patients and propagated in eggs. We determined viral load that infects 50% of eggs (50% egg lethal dose, ELD50). We introduced 10 ELD50 into embryonated eggs and repeated the experiments using 100 ELD50. A mixture of zinc oxide (Zn) and trimethoprim (TMP) (weight / weight ratios ranged from 0.01 to 0.3, Zn/TMP with increment of 0.1) was tested for embryo survival of the infection (n = 12 per ratio, in triplicates). Embryo survival was determined by candling eggs daily for 7 days. Controls of Zn, TMP, saline or convalescent serum were conducted in parallel. The effect of Tri-Z on virus binding to its cell surface receptor was evaluated in a hemagglutination inhibition (HAI) assay using chicken red cells. HAI effect was expressed as scores where ++++ = no effect; 0 = complete HAI effect.Results. TMP, Zn or saline separately had no effect on embryo survival, none of the embryos survived influenza virus infection. All embryos treated with convalescent serum survived. Tri-Z, at ratio range of 0.15 to 0.2 (optimal ratio of 0.18) Zn / TMP, enabled embryos to survive influenza virus despite increasing viral load (>80% survival at optimal ratio). At concentration of 15 microgram/ml of optimal ratio, Tri-Z had total HAI effect (scored 0). However, at clinical concentration of 5 microgram/ml, Tri-Z had partial HAI effect (++).Conclusion. Acting on host cells, Tri-Z at optimal ratio can reduce the lethal effect of influenza A virus in chick embryo. Tri-Z has HAI effect. These findings suggest that combination of trimethoprim and zinc at optimal ratio can be provided as treatment for influenza and possibly other respiratory RNA viruses infection in man.

Exacerbation of disease by intranasal liquid administration following influenza virus infection in mice

2020 ◽  
Vol 78 (2) ◽  
Author(s):  
Yuanjun Lyu ◽  
Pengcheng Li ◽  
Zifeng Yang ◽  
Nanshan Zhong
Keyword(s):  
Mouse Models ◽  
Influenza A ◽  
Secondary Infection ◽  
Survival Rates ◽  
Influenza Virus Infection ◽  
Dual Infection ◽  
Lung Damage ◽  
Infection Model ◽  
Lung Pathology ◽  
Infectious Dose

ABSTRACT Although numerous studies have clarified the synergistic pathogenesis in mouse models of influenza A virus (IAV)-associated dual infections, fewer studies have investigated the influence of intranasal liquid administration on the disease. This study explored the effects of intranasal PBS administration in mouse models of mimic IAV dual infection and the infectious dose of IAV that caused equivalent pathogenesis in different dual infection models. Weights, survival rates, virus loads, lung indexes and lung pathology were compared. We demonstrated that intranasal PBS administration following H1N1 or H3N2 infection increased weight loss, mortality, virus replication and lung damage. No difference was observed if the order was reversed or PBS was given simultaneously with IAV. To induce equivalent virulence, a 20-fold difference in the infectious dose was needed when the H3N2–PBS superinfection and H3N2–PBS coinfection or PBS–H3N2 superinfection groups were compared. Our study demonstrated that the unfavourable effect of intranasal liquid administration should not be neglected and that both the strain and infectious dose of IAV should be considered to avoid an illusion of synergistic pathogenicity when establishing IAV-associated dual infection model. A 20-fold lower dose than that of coinfection may be a better choice for secondary infection following IAV.

scholarly journals Combination therapy of zinc and trimethoprim inhibits infection of influenza A virus in chick embryo

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Magdi H. El Habbal
Keyword(s):  
Influenza Virus ◽  
Viral Load ◽  
Chick Embryo ◽  
Influenza A Virus ◽  
Influenza A ◽  
Rna Viruses ◽  
Influenza Virus Infection ◽  
Lethal Effect ◽  
Embryo Survival ◽  
Optimal Ratio

Abstract Background Respiratory RNA viruses including influenza virus have been a cause of health and economic hardships. These viruses depend on its host for replication and infection. Influenza virus infection is lethal to the chick embryo. We examined whether a combination of trimethoprim and zinc (Tri-Z), that acts on the host, can reduce the lethal effect of influenza A virus in chick embryo model. Method Influenza virus was isolated from patients and propagated in eggs. We determined viral load that infects 50% of eggs (50% egg lethal dose, ELD50). We introduced 10 ELD50 into embryonated eggs and repeated the experiments using 100 ELD50. A mixture of zinc oxide (Zn) and trimethoprim (TMP) (weight/weight ratios ranged from 0.01 to 0.3, Zn/TMP with increment of 0.1) was tested for embryo survival of the infection (n = 12 per ratio, in triplicates). Embryo survival was determined by candling eggs daily for 7 days. Controls of Zn, TMP, saline or convalescent serum were conducted in parallel. The effect of Tri-Z on virus binding to its cell surface receptor was evaluated in a hemagglutination inhibition (HAI) assay using chicken red cells. Tri-Z was prepared to concentration of 10 mg TMP and 1.8 mg Zn per ml, then serial dilutions were made. HAI effect was expressed as scores where ++++ = no effect; 0 = complete HAI effect. Results TMP, Zn or saline separately had no effect on embryo survival, none of the embryos survived influenza virus infection. All embryos treated with convalescent serum survived. Tri-Z, at ratio range of 0.15–0.2 (optimal ratio of 0.18) Zn/TMP, enabled embryos to survive influenza virus despite increasing viral load (> 80% survival at optimal ratio). At concentration of 15 µg/ml of optimal ratio, Tri-Z had total HAI effect (scored 0). However, at clinical concentration of 5 µg/ml, Tri-Z had partial HAI effect (+ +). Conclusion Acting on host cells, Tri-Z at optimal ratio can reduce the lethal effect of influenza A virus in chick embryo. Tri-Z has HAI effect. These findings suggest that combination of trimethoprim and zinc at optimal ratio can be provided as treatment for influenza and possibly other respiratory RNA viruses infection in man.

Five-Lump Kinetic Model for the Catalytic Cracking Process\

2018 ◽  
Vol 69 (10) ◽  
pp. 2633-2637
Author(s):  
Raluca Dragomir ◽  
Paul Rosca ◽  
Cristina Popa
Keyword(s):  
Kinetic Model ◽  
Programming Language ◽  
Catalytic Cracking ◽  
Computational Method ◽  
Industrial Data ◽  
New Model ◽  
Optimization And Control ◽  
Cracking Process ◽  
And Control ◽  
Matlab Programming

The main objectives of the present paper are to adaptation the five-kinetic model of the catalytic cracking process and simulation the riser to predicts the FCC products yields when one of the major input variable of the process is change. The simulation and adaptation are based on the industrial data from Romanian refinery. The adaptation is realize using a computational method from Optimization Toolbox from Matlab programming language. The new model can be used for optimization and control of FCC riser.

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.

scholarly journals Influenza A Virus Hemagglutinin and Other Pathogen Glycoprotein Interactions with NK Cell Natural Cytotoxicity Receptors NKp46, NKp44, and NKp30

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 156
Author(s):  
Jasmina M. Luczo ◽  
Sydney L. Ronzulli ◽  
Stephen M. Tompkins
Keyword(s):  
Influenza Virus ◽  
Nk Cells ◽  
Influenza A Virus ◽  
Influenza A ◽  
Nk Cell ◽  
Influenza Virus Infection ◽  
Target Cells ◽  
Natural Cytotoxicity ◽  
Activating Receptors ◽  
Natural Cytotoxicity Receptors

Natural killer (NK) cells are part of the innate immunity repertoire, and function in the recognition and destruction of tumorigenic and pathogen-infected cells. Engagement of NK cell activating receptors can lead to functional activation of NK cells, resulting in lysis of target cells. NK cell activating receptors specific for non-major histocompatibility complex ligands are NKp46, NKp44, NKp30, NKG2D, and CD16 (also known as FcγRIII). The natural cytotoxicity receptors (NCRs), NKp46, NKp44, and NKp30, have been implicated in functional activation of NK cells following influenza virus infection via binding with influenza virus hemagglutinin (HA). In this review we describe NK cell and influenza A virus biology, and the interactions of influenza A virus HA and other pathogen lectins with NK cell natural cytotoxicity receptors (NCRs). We review concepts which intersect viral immunology, traditional virology and glycobiology to provide insights into the interactions between influenza virus HA and the NCRs. Furthermore, we provide expert opinion on future directions that would provide insights into currently unanswered questions.

scholarly journals A New Model for the Stochastic Point Reactor: Development and Comparison with Available Models

Energies ◽  
2021 ◽  
Vol 14 (4) ◽  
pp. 955
Author(s):  
Alamir Elsayed ◽  
Mohamed El-Beltagy ◽  
Amnah Al-Juhani ◽  
Shorooq Al-Qahtani
Keyword(s):  
Kinetic Model ◽  
Differential Equations ◽  
Test Cases ◽  
System Of Differential Equations ◽  
Reactor Model ◽  
Time System ◽  
New Model ◽  
Reactor Dynamics ◽  
Mean And Variance ◽  
The Mean

The point kinetic model is a system of differential equations that enables analysis of reactor dynamics without the need to solve coupled space-time system of partial differential equations (PDEs). The random variations, especially during the startup and shutdown, may become severe and hence should be accounted for in the reactor model. There are two well-known stochastic models for the point reactor that can be used to estimate the mean and variance of the neutron and precursor populations. In this paper, we reintroduce a new stochastic model for the point reactor, which we named the Langevin point kinetic model (LPK). The new LPK model combines the advantages, accuracy, and efficiency of the available models. The derivation of the LPK model is outlined in detail, and many test cases are analyzed to investigate the new model compared with the results in the literature.

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