Mathematical Modeling of Dengue Virus Control and Vaccination Method

Algebraic modeling the infectious syndrome is expedient to nurture the appliance in pardon method syndrome suckers and in pardon method splendid. Now consume deliberate in ascending order the dengue virus. Now edge the totally limitless Non-Standard Finite Difference (NSFD) construction bound for a mathematical typical the dengue virus. The explain numerical display is limited, dynamically label and comprise the positivity of the explanation, who is central rations so modeling a dominant infectious. The contrast amongst the original Non-Standard Finite Change erection, Euler technique and Runge-Kutta organization of instruction four (RK-4) parades the worth of the proposed Non-Standard Finite Change scheme. Explicit NSFD scheme displays meeting the careful evenness truths of the perfect for any value increase or decrease but Euler and RK-4 fail for huge change value. Keywords: Dengue Virus, Dynamical System, Numerical Modeling, Convergence. DOI: 10.7176/MTM/9-4-01 Publication date: April 30th 2019

Numerically Modeling Solve by Homotopy Perturbation Method

In this paper, we used the homotopy perturbation method (HPM) to obtain a different approximate solutions of the Cauchy problem using in one dimensional nonlinear thermoelasticity. The comparison of the numerical solutions obtained by HPM with the exact solution shows the efficiency of the method of HPM. Keywords: Homotopy perturbation method, Cauchy problem, nonlinear thermoelasticity, analytical approximate solution. DOI: 10.7176/MTM/9-4-03 Publication date: April 30th 2019

Numerical Modeling for Transmission Dynamics of Hepatitis B Virus Disease

Numerical modeling of communicable disease is a device to appreciate the instrument in what way syndrome pushovers and in what way stately. we have studied numerically the dynamics of HBV. We frame an entirely constant Non-Standard Finite Difference (NSFD) structure for a mathematical model of HBV. The introduce numerical array is bounded, dynamically designate and contain the positivity of the solution, which is one of the important requirements when modeling a prevalent contagious. The comparison between the innovative Non-Standard Finite Alteration structure, Euler method and Runge-Kutta scheme of order four (RK-4) displays the usefulness of the suggested Non-Standard Finite Alteration scheme. NSFD scheme shows convergence to the exact equilibrium facts of the model for any time steps used but Euler and RK-4 fail for large time steps. Keywords: Hepatitis B Disease, Dynamical System, Numerical Modeling, Convergence. DOI: 10.7176/MTM/9-1-04

Dual HLA B*42 and B*81-reactive T cell receptors recognize more diverse HIV-1 Gag escape variants

Closely related HLA alleles presenting similar HIV-1 epitopes can be associated with variable clinical outcome. Here the authors report their findings on CD8+ T cell responses to the HIV-1 Gag-p24 TL9 immunodominant epitope in the context of closely related protective and less protective HLA alleles, and their differential effect on viral contro

Augmentation of HIV-specific T cell function by immediate treatment of hyperacute HIV-1 infection

Sustained viremia after acute HIV infection is associated with profound CD4+ T cell loss and exhaustion of HIV-specific CD8+ T cell responses. To determine the impact of combination antiretroviral therapy (cART) on these processes, we examined the evolution of immune responses in acutely infected individuals initiating treatment before peak viremia. Immediate treatment of Fiebig stages I and II infection led to a rapid decline in viral load and diminished magnitude of HIV-specific (tetramer+) CD8+ T cell responses compared to untreated donors. There was a strong positive correlation between cumulative viral antigen exposure before full cART-induced suppression and immune responses measured by MHC class I tetramers, IFN-γ ELISPOT, and CD8+ T cell activation. HIV-specific CD8+ T responses of early treated individuals were characterized by increased CD127 and BCL-2 expression, greater in vitro IFN-γ secretion, and enhanced differentiation into effector memory (Tem) cells. Transcriptional analysis of tetramer+ CD8+ T cells from treated persons revealed reduced expression of genes associated with activation and apoptosis, with concurrent up-regulation of prosurvival genes including BCL-2, AXL, and SRC. Early treatment also resulted in robust HIV-specific CD4+ T cell responses compared to untreated HIV-infected individuals. Our data show that limiting acute viremia results in enhanced functionality of HIV-specific CD4+ and CD8+ T cells, preserving key antiviral properties of these cells

Nef-mediated down-regulation of CD4 and HLA class I in HIV-1 subtype C infection: association with disease progression and influence of immune pressure.

CAPRISA, 2014.Abstract available in pdf

A mechanistic investigation of T cell receptor-mediated HIV control

HIV remains a global pandemic. No vaccine or cure exists. Most infected individuals progress to AIDS in the absence of antiretroviral therapy, but a rare group of elite controllers (<0.5% of the infected population) suppresses viremia to an undetectable level. HIV control is often associated with a robust host immune response, mediated by selected HLA alleles that elicit T cells against more conserved HIV peptide epitopes. T cell recognition of an infected cell is determined by its unique T cell receptor (TCR), which binds a virus-derived peptide presented on the cell surface by an HLA protein. An individual’s repertoire of TCR clones is large, but finite, and varies even among those who express the same HLA alleles. TCR sequence differences between controllers and non-controllers have been associated with variation in the antiviral activity of T cells, but few studies have explored this question comprehensively. My thesis project aims to identify TCR features that contribute to HIV control. To do this, I examined CD8+ T cell responses against the immunodominant HIV Gag TL9 (TPQDLNTML) epitope. TL9 is presented by HLA-B*42 and B*81, but only B*81 is associated with HIV control. I sequenced TCR from TL9-specific T cells, including dual-reactive cells associated with HIV control in B*42 individuals that recognized TL9 presented by both B*42 and B*81, and then conducted functional and structural assessments of selected TCR clones. TL9-specific TCR from B*81 individuals and dual-reactive TCR from B*42 individuals were highly enriched for TRBV12-3 gene usage. Furthermore, dual-reactive TCR from B*42 individuals were dominated by shared (or public) clones. Comprehensive functional analyses revealed that TCR from B*81 individuals and dual-reactive TCR from B*42 individuals displayed greater capacity to recognize TL9 variants, including common HIV escape mutations. Structural analyses of two dual-reactive TCR clones demonstrated an unusual peptide binding conformation driven by TRBV12-3 germline residues. My results demonstrate that clonal differences in the ability of TCR to recognize TL9 variants are associated with HIV control. Functional and structural data provide mechanistic insight into key features of more effective TL9-specific TCR. By highlighting the impact of TCR clonotype on HIV control, my results will inform development of new vaccine and therapeutic strategies

Dual HLA B*42 and B*81-reactive T cell receptors recognize more diverse HIV-1 Gag escape variants

Closely related HLA alleles presenting similar HIV-1 epitopes can be associated with variable clinical outcome. Here the authors report their findings on CD8+ T cell responses to the HIV-1 Gag-p24 TL9 immunodominant epitope in the context of closely related protective and less protective HLA alleles, and their differential effect on viral contro

Augmentation of HIV-specific T cell function by immediate treatment of hyperacute HIV-1 infection

Sustained viremia after acute HIV infection is associated with profound CD4⁺ T cell loss and exhaustion of HIV-specific CD8⁺ T cell responses. To determine the impact of combination antiretroviral therapy (cART) on these processes, we examined the evolution of immune responses in acutely infected individuals initiating treatment before peak viremia. Immediate treatment of Fiebig stages I and II infection led to a rapid decline in viral load and diminished magnitude of HIV-specific (tetramer⁺) CD8⁺ T cell responses compared to untreated donors. There was a strong positive correlation between cumulative viral antigen exposure before full cART-induced suppression and immune responses measured by MHC class I tetramers, IFN-γ ELISPOT, and CD8⁺ T cell activation. HIV-specific CD8⁺ T responses of early treated individuals were characterized by increased CD127 and BCL-2 expression, greater in vitro IFN-γ secretion, and enhanced differentiation into effector memory (Tₑₘ) cells. Transcriptional analysis of tetramer⁺ CD8⁺ T cells from treated persons revealed reduced expression of genes associated with activation and apoptosis, with concurrent up-regulation of prosurvival genes including BCL-2, AXL, and SRC. Early treatment also resulted in robust HIV-specific CD4⁺ T cell responses compared to untreated HIV-infected individuals. Our data show that limiting acute viremia results in enhanced functionality of HIV-specific CD4⁺ and CD8⁺ T cells, preserving key antiviral properties of these cells.National Institute of Health (U.S.) (5U24AI118672)National Institute of Health (U.S.) (1U54CA217377)National Institute of Health (U.S.) (1R33CA202820)National Institute of Health (U.S.) (2U19AI089992)National Institute of Health (U.S.) (1R01HL134539)National Institute of Health (U.S.) (2RM1HG006193)National Institute of Health (U.S.) (2R01HL095791)National Institute of Health (U.S.) (P01AI039671)Bill and Melinda Gates Foundation (OPP1139972

In vitro functional assessment of natural HIV-1 group M Vpu sequences using a universal priming approach

The HIV-1 accessory protein Vpu exhibits high inter- and intra- subtype genetic diversity that may influence Vpu function and possibly contribute to HIV-1 pathogenesis. However, scalable methods to evaluate genotype/phenotype relationships in natural Vpu sequences are limited, particularly those expressing the protein in CD4+ T-cells, the natural target of HIV-1 infection. A major impediment to assay scalability is the extensive genetic diversity within, and immediately upstream of, Vpu's initial 5' coding region, which has necessitated the design of oligonucleotide primers specific for each individual HIV-1 isolate (or subtype). To address this, we developed two universal forward primers, located in relatively conserved regions 38 and 90 bases upstream of Vpu, and a single universal reverse primer downstream of Vpu, which are predicted to cover the vast majority of global HIV-1 group M sequence diversity. We show that inclusion of up to 90 upstream bases of HIV-1 genomic sequence does not significantly influence in vitro Vpu expression or function when a Rev/Rev Response Element (RRE)-dependent expression system is used. We further assess the function of four diverse HIV-1 Vpu sequences, revealing reproducible and significant differences between them. Our approach represents a scalable option to measure the in vitro function of genetically diverse natural Vpu isolates in a CD4+ T-cell line