Discrete biological modeling for the immune response to dengue virus

Dengue infection affects more than half of the world’s population, with 1 billion symptomatic cases identified per year and several distinct genetic serotypes: DENV 1–4. Transmitted via the mosquito bite, the dengue virus infects Langerhans cells. Monocytes, B lymphocytes, and mast cells infected with dengue virus produce various cytokines although it is not clear which ones are predominant during DHF disease. A mathematical model of the Dengue virus infection is developed according to complex dynamics determined by many factors. Starting from a state of equilibrium that we could define as “virus-free” asymptotically stable with a viral reproduction number lower than one which means a very effective action of the innate immune system: it stops the infectious process, the mathematical analysis of stability in the presence of the virus demonstrates that the proposed model is dynamically influenced. Dengue fever affects more than half of the world’s population, with 1 billion symptomatic cases and multiple genetic serotypes confirmed each year, which simulates a network of interactions between the various populations involved without considering the speeds of the processes in question which are indicated in a separate computation. In this research, a hybrid approach of petri nets is utilized to connect the discrete models of dengue.

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Impact of Humoral Immune Response and Absorption Effect on Dynamics of Dengue Virus

European Scientific Journal ESJ ◽

10.19044/esj.2017.v13n12p157 ◽

2017 ◽

Vol 13 (12) ◽

pp. 157

Author(s):

S.D. Perera ◽

S.S.N. Perera

Keyword(s):

Immune Response ◽

Dengue Virus ◽

Humoral Immune Response ◽

Dengue Infection ◽

Endemic Equilibrium ◽

Absorption Effect ◽

Globally Asymptotically Stable ◽

Humoral Immune ◽

Proposed Model ◽

Global Threat

Dengue infection represents a global threat causing 50-100 million infections per year and placing half of the world’s population at risk. Even though how infection is controlled and cured rather remains a mystery, antibodies are thought to play a major role in clearing the virus. In this paper, we study the dynamics of dengue virus with humoral immune response and absorption effect. The proposed model incorporates a time delay in production of antibodies. The basic reproduction number R0 is computed and a detailed stability analysis is done. It was found that the model has 3 steady states, namely, infection free equilibrium, no immune equilibrium and the endemic equilibrium. Conditions for R0 were developed for the local stability of these 3 equilibrium states. The global stability was studied using appropriate Lyapunov function and LaSalle’s invariance principle. We then established a condition for which the endemic equilibrium point is globally asymptotically stable. Also it was observed that the virus count goes to negligible levels within 7-14 days after the onset of symptoms.

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Novel phenotype of Wolbachia strain wPip in Aedes aegypti challenges assumptions on mechanisms of Wolbachia-mediated dengue virus inhibition

10.1101/2020.02.20.957423 ◽

2020 ◽

Cited By ~ 1

Author(s):

Johanna E. Fraser ◽

Tanya B. O’Donnell ◽

Johanna M. Duyvestyn ◽

Scott L. O’Neill ◽

Cameron P. Simmons ◽

...

Keyword(s):

Aedes Aegypti ◽

Dengue Virus ◽

Dengue Infection ◽

Innate Immune ◽

Control Programs ◽

Virus Inhibition ◽

Limited Efficacy ◽

Positive Sense ◽

Pathogenic Viruses ◽

Human Infections

AbstractThe bacterial endosymbiont Wolbachia is a biocontrol tool that inhibits the ability of the Aedes aegypti mosquito to transmit positive-sense RNA viruses such as dengue and Zika. Growing evidence indicates that when Wolbachia strains wMel or wAlbB are introduced into local mosquito populations, human dengue incidence is reduced. Despite the success of this novel intervention, we still do not fully understand how Wolbachia protects mosquitoes from viral infection. Here, we demonstrate that the Wolbachia strain wPip does not inhibit virus infection in Ae. aegypti. We have leveraged this novel finding, and a panel of Ae. aegypti lines carrying virus-inhibitory (wMel and wAlbB) and non-inhibitory (wPip) strains in a common genetic background, to rigorously test a number of hypotheses about the mechanism of Wolbachia-mediated virus inhibition. We demonstrate that, contrary to previous suggestions, there is no association between a strain’s ability to inhibit dengue infection in the mosquito and either its typical density in the midgut or salivary glands, or the degree to which it elevates innate immune response pathways in the mosquito. These findings, and the experimental platform provided by this panel of genetically comparable mosquito lines, clear the way for future investigations to define how Wolbachia prevents Ae. aegypti from transmitting viruses.Author summaryDengue virus, transmitted by the Aedes aegypti mosquito, is one of the fastest-growing infectious diseases, causing an estimated 390 million human infections per year worldwide. Vaccines have limited efficacy and there are no approved therapeutics. This has driven the rise of novel vector control programs, in particular those that use the bacterium, Wolbachia, which prevents transmission of dengue and other human pathogenic viruses when stably introduced into Ae. aegypti populations. Although this is proving to be a highly effective method, the details of how this biocontrol tool works are not well understood. Here we characterise a new Wolbachia strain, wPip, and find that Ae. aegypti carrying wPip are still able to transmit dengue similar to mosquitoes that do not carry Wolbachia. This finding has allowed us to begin a rigorous program of comparative studies to determine which features of a Wolbachia strain determine whether it is antiviral. Understanding these mechanisms will enable us to predict the risk of viral resistance arising against Wolbachia and facilitate preparation of second-generation field release lines.

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The Lethal(2)-Essential-for-Life [L(2)EFL] Gene Family Modulates Dengue Virus Infection in Aedes aegypti

International Journal of Molecular Sciences ◽

10.3390/ijms21207520 ◽

2020 ◽

Vol 21 (20) ◽

pp. 7520

Author(s):

Lucky R. Runtuwene ◽

Shuichi Kawashima ◽

Victor D. Pijoh ◽

Josef S. B. Tuda ◽

Kyoko Hayashida ◽

...

Keyword(s):

Aedes Aegypti ◽

Dengue Virus ◽

Cell Line ◽

Dengue Infection ◽

Fruit Fly ◽

Initiation Factor ◽

Poly I:C ◽

Gene Products ◽

Vector Mosquito

Efforts to determine the mosquito genes that affect dengue virus replication have identified a number of candidates that positively or negatively modify amplification in the invertebrate host. We used deep sequencing to compare the differential transcript abundances in Aedes aegypti 14 days post dengue infection to those of uninfected A. aegypti. The gene lethal(2)-essential-for-life [l(2)efl], which encodes a member of the heat shock 20 protein (HSP20) family, was upregulated following dengue virus type 2 (DENV-2) infection in vivo. The transcripts of this gene did not exhibit differential accumulation in mosquitoes exposed to insecticides or pollutants. The induction and overexpression of l(2)efl gene products using poly(I:C) resulted in decreased DENV-2 replication in the cell line. In contrast, the RNAi-mediated suppression of l(2)efl gene products resulted in enhanced DENV-2 replication, but this enhancement occurred only if multiple l(2)efl genes were suppressed. l(2)efl homologs induce the phosphorylation of eukaryotic initiation factor 2α (eIF2α) in the fruit fly Drosophila melanogaster, and we confirmed this finding in the cell line. However, the mechanism by which l(2)efl phosphorylates eIF2α remains unclear. We conclude that l(2)efl encodes a potential anti-dengue protein in the vector mosquito.

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Serum Metabolomics Investigation of Humanized Mouse Model of Dengue Virus Infection

Journal of Virology ◽

10.1128/jvi.00386-17 ◽

2017 ◽

Vol 91 (14) ◽

Cited By ~ 11

Author(s):

Liang Cui ◽

Jue Hou ◽

Jinling Fang ◽

Yie Hou Lee ◽

Vivian Vasconcelos Costa ◽

...

Keyword(s):

Fatty Acids ◽

Animal Model ◽

Bile Acid ◽

Dengue Virus ◽

Metabolic Pathways ◽

Dengue Infection ◽

Small Animal ◽

Humanized Mice ◽

Small Animal Model ◽

Serum Metabolomics

ABSTRACT Dengue is an acute febrile illness caused by dengue virus (DENV) and a major cause of morbidity and mortality in tropical and subtropical regions of the world. The lack of an appropriate small-animal model of dengue infection has greatly hindered the study of dengue pathogenesis and the development of therapeutics. In this study, we conducted mass spectrometry-based serum metabolic profiling from a model using humanized mice (humice) with DENV serotype 2 infection at 0, 3, 7, 14, and 28 days postinfection (dpi). Forty-eight differential metabolites were identified, including fatty acids, purines and pyrimidines, acylcarnitines, acylglycines, phospholipids, sphingolipids, amino acids and derivatives, free fatty acids, and bile acid. These metabolites showed a reversible-change trend—most were significantly perturbed at 3 or 7 dpi and returned to control levels at 14 or 28 dpi, indicating that the metabolites might serve as prognostic markers of the disease in humice. The major perturbed metabolic pathways included purine and pyrimidine metabolism, fatty acid β-oxidation, phospholipid catabolism, arachidonic acid and linoleic acid metabolism, sphingolipid metabolism, tryptophan metabolism, phenylalanine metabolism, lysine biosynthesis and degradation, and bile acid biosynthesis. Most of these disturbed pathways are similar to our previous metabolomics findings in a longitudinal cohort of adult human dengue patients across different infection stages. Our analyses revealed the commonalities of host responses to DENV infection between humice and humans and suggested that humice could be a useful small-animal model for the study of dengue pathogenesis and the development of dengue therapeutics. IMPORTANCE Dengue virus is the most widespread arbovirus, causing an estimated 390 million dengue infections worldwide every year. There is currently no effective treatment for the disease, and the lack of an appropriate small-animal model of dengue infection has greatly increased the challenges in the study of dengue pathogenesis and the development of therapeutics. Metabolomics provides global views of small-molecule metabolites and is a useful tool for finding metabolic pathways related to disease processes. Here, we conducted a serum metabolomics study on a model using humanized mice with dengue infection that had significant levels of human platelets, monocytes/macrophages, and hepatocytes. Forty-eight differential metabolites were identified, and the underlying perturbed metabolic pathways are quite similar to the pathways found to be altered in dengue patients in previous metabolomics studies, indicating that humanized mice could be a highly relevant small-animal model for the study of dengue pathogenesis and the development of dengue therapeutics.

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KGPMH: A hybrid approach for solving a novel facility location problem

10.36227/techrxiv.16866895.v1 ◽

2021 ◽

Author(s):

Maryam DehghanChenary ◽

Arman Ferdowsi ◽

Fariborz Jolai ◽

Reza Tavakkoli-Moghaddam

Keyword(s):

Mathematical Model ◽

Location Problem ◽

Hybrid Approach ◽

Facility Location Problem ◽

Evaluation Function ◽

Genetic Approach ◽

Hub Location ◽

Hub Location Problem ◽

Proposed Model ◽

The Impact

<pre>The focus of this paper is to propose a bi-objective mathematical model for a new extension of a multi-period p-mobile hub location problem and then to devise an algorithm for solving it. The developed model considers the impact of the time spent traveling at the hubs' network, the time spent at hubs for processing the flows, and the delay caused by congestion at hubs with specific capacities. Following the unveiled model, a hybrid meta-heuristic algorithm will be devised that simultaneously takes advantage of a novel evaluation function, a clustering technique, and a genetic approach for solving the proposed model.</pre>

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Comparison of Seven Commercial Antigen and Antibody Enzyme-Linked Immunosorbent Assays for Detection of Acute Dengue Infection

Clinical and Vaccine Immunology ◽

10.1128/cvi.05717-11 ◽

2012 ◽

Vol 19 (5) ◽

pp. 804-810 ◽

Cited By ~ 76

Author(s):

Stuart D. Blacksell ◽

Richard G. Jarman ◽

Robert V. Gibbons ◽

Ampai Tanganuchitcharnchai ◽

Mammen P. Mammen ◽

...

Keyword(s):

South Korea ◽

Dengue Virus ◽

Dengue Infection ◽

Virus Antigen ◽

Enzyme Linked Immunosorbent Assay ◽

Capture Elisa ◽

Igm Antibody ◽

Antigen Elisa ◽

Ns1 Antigen ◽

Elisa Format

ABSTRACTSeven commercial assays were evaluated to determine their suitability for the diagnosis of acute dengue infection: (i) the Panbio dengue virus Pan-E NS1 early enzyme-linked immunosorbent assay (ELISA), second generation (Alere, Australia); (ii) the Panbio dengue virus IgM capture ELISA (Alere, Australia); (iii) the Panbio dengue virus IgG capture ELISA (Alere, Australia); (iv) the Standard Diagnostics dengue virus NS1 antigen ELISA (Standard Diagnostics, South Korea); (v) the Standard Diagnostics dengue virus IgM ELISA (Standard Diagnostics, South Korea); (vi) the Standard Diagnostics dengue virus IgG ELISA (Standard Diagnostics, South Korea); and (vii) the Platelia NS1 antigen ELISA (Bio-Rad, France). Samples from 239 Thai patients confirmed to be dengue virus positive and 98 Sri Lankan patients negative for dengue virus infection were tested. The sensitivities and specificities of the NS1 antigen ELISAs ranged from 45 to 57% and 93 to 100% and those of the IgM antibody ELISAs ranged from 85 to 89% and 88 to 100%, respectively. Combining the NS1 antigen and IgM antibody results from the Standard Diagnostics ELISAs gave the best compromise between sensitivity and specificity (87 and 96%, respectively), as well as providing the best sensitivity for patients presenting at different times after fever onset. The Panbio IgG capture ELISA correctly classified 67% of secondary dengue infection cases. This study provides strong evidence of the value of combining dengue virus antigen- and antibody-based test results in the ELISA format for the diagnosis of acute dengue infection.

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Acute dengue virus 2 infection in Gabonese patients is associated with an early innate immune response, including strong interferon alpha production

BMC Infectious Diseases ◽

10.1186/1471-2334-10-356 ◽

2010 ◽

Vol 10 (1) ◽

Cited By ~ 38

Author(s):

Pierre Becquart ◽

Nadia Wauquier ◽

Dieudonné Nkoghe ◽

Angélique Ndjoyi-Mbiguino ◽

Cindy Padilla ◽

...

Keyword(s):

Immune Response ◽

Dengue Virus ◽

Interferon Alpha ◽

Innate Immune Response ◽

Innate Immune ◽

Alpha Production

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Simulation Model for Dynamics of Dengue with Innate and Humoral Immune Responses

Computational and Mathematical Methods in Medicine ◽

10.1155/2018/8798057 ◽

2018 ◽

Vol 2018 ◽

pp. 1-18 ◽

Cited By ~ 3

Author(s):

S. D. Perera ◽

S. S. N. Perera

Keyword(s):

Immune Response ◽

Immune Responses ◽

Dengue Virus ◽

Dengue Infection ◽

Asymptomatic Infection ◽

Severe Dengue ◽

Viral Kinetics ◽

Humoral Immune ◽

Humoral Immune Responses ◽

Kinetics Of

Dengue virus is a mosquito borne Flavivirus and the most prevalent arbovirus in tropical and subtropical regions around the world. The incidence of dengue has increased drastically over the last few years at an alarming rate. The clinical manifestation of dengue ranges from asymptomatic infection to severe dengue. Even though the viral kinetics of dengue infection is lacking, innate immune response and humoral immune response are thought to play a major role in controlling the virus count. Here, we developed a computer simulation mathematical model including both innate and adaptive immune responses to study the within-host dynamics of dengue virus infection. A sensitivity analysis was carried out to identify key parameters that would contribute towards severe dengue. A detailed stability analysis was carried out to identify relevant range of parameters that contributes to different outcomes of the infection. This study provides a qualitative understanding of the biological factors that can explain the viral kinetics during a dengue infection.

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Complete Genome Sequences of Dengue Virus Type 2 Strains from Kilifi, Kenya

Microbiology Resource Announcements ◽

10.1128/mra.01566-18 ◽

2019 ◽

Vol 8 (4) ◽

Cited By ~ 7

Author(s):

Everlyn Kamau ◽

Charles N. Agoti ◽

Joyce M. Ngoi ◽

Zaydah R. de Laurent ◽

John Gitonga ◽

...

Keyword(s):

Dengue Virus ◽

Virus Type ◽

Complete Genome ◽

Sequence Data ◽

Dengue Infection ◽

Clinical Samples ◽

Genome Sequences ◽

Coastal Kenya ◽

Dengue Virus Type 2

Dengue infection remains poorly characterized in Africa and little is known regarding its associated viral genetic diversity. Here, we report dengue virus type 2 (DENV-2) sequence data from 10 clinical samples, including 5 complete genome sequences of the cosmopolitan genotype, obtained from febrile adults seeking outpatient care in coastal Kenya.

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