scholarly journals HTLV/HIV Dual Infection: Modeling and Analysis

Mathematics ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 51
Author(s):  
Ahmed M. Elaiw ◽  
Noura H. AlShamrani
Keyword(s):  
Asymptotic Stability ◽  
Dual Infection ◽  
Steady States ◽  
Single Infection ◽  
Infection Model ◽  
Type I ◽  
Modeling And Analysis ◽  
Specific Ctls ◽  
Infected Cells ◽  
The Impact

Human T-lymphotropic virus type I (HTLV-I) and human immunodeficiency virus (HIV) are two famous retroviruses that share similarities in their genomic organization, and differ in their life cycle as well. It is known that HTLV-I and HIV have in common a way of transmission via direct contact with certain body fluids related to infected patients. Thus, it is not surprising that a single-infected person with one of these viruses can be dually infected with the other virus. In the literature, many researchers have devoted significant efforts for modeling and analysis of HTLV or HIV single infection. However, the dynamics of HTLV/HIV dual infection has not been formulated. In the present paper, we formulate an HTLV/HIV dual infection model. The model includes the impact of the Cytotoxic T lymphocyte (CTLs) immune response, which is important to control the dual infection. The model describes the interaction between uninfected CD4+T cells, HIV-infected cells, HTLV-infected cells, free HIV particles, HIV-specific CTLs, and HTLV-specific CTLs. We establish that the solutions of the model are non-negative and bounded. We calculate all steady states of the model and deduce the threshold parameters which determine the existence and stability of the steady states. We prove the global asymptotic stability of all steady states by utilizing the Lyapunov function and Lyapunov–LaSalle asymptotic stability theorem. We solve the system numerically to illustrate the our main results. In addition, we compared between the dynamics of single and dual infections.

Modeling and stability analysis of HIV/HTLV-I co-infection

2021 ◽  
pp. 2150030
Author(s):  
A. M. Elaiw ◽  
N. H. AlShamrani
Keyword(s):  
T Cells ◽  
Infection Model ◽  
Type I ◽  
Infected Person ◽  
T Lymphotropic Virus ◽  
Specific Ctls ◽  
Immunodeficiency Virus ◽  
Existence And Stability ◽  
Infected Cells ◽  
The Impact

Human immunodeficiency virus (HIV) and human T-lymphotropic virus type I (HTLV-I) are two retroviruses that infect the susceptible CD[Formula: see text]T cells. It is known that HIV and HTLV-I have in common a way of transmission through direct contact with certain body fluids related to infected individuals. Therefore, it is not surprising that a mono-infected person with one of these viruses can be co-infected with the other virus. In the literature, a great number of mathematical models has been presented to describe the within-host dynamics of HIV or HTLV-I mono-infection. However, the within-host dynamics of HIV/HTLV-I co-infection has not been modeled. In this paper, we develop a new within-host HIV/HTLV-I co-infection model. The model includes the impact of Cytotoxic T lymphocytes (CTLs) immune response, which is important to control the progression of viral co-infection. The model describes the interaction between susceptible CD[Formula: see text]T cells, silent HIV-infected cells, active HIV-infected cells, silent HTLV-infected cells, Tax-expressing HTLV-infected cells, free HIV particles, HIV-specific CTLs and HTLV-specific CTLs. We first show the nonnegativity and boundedness of the model’s solutions and then we calculate all possible equilibria. We derive the threshold parameters which govern the existence and stability of all equilibria of the model. We prove the global asymptotic stability of all equilibria by utilizing Lyapunov function and LaSalle’s invariance principle. We have presented numerical simulations to illustrate the effectiveness of our main results. In addition, we discuss the effect of HTLV-I infection on the HIV-infected patients and vice versa.

scholarly journals Analysis of an HTLV/HIV dual infection model with diffusion

2021 ◽  
Vol 18 (6) ◽  
pp. 9430-9473
Author(s):  
A. M. Elaiw ◽  
◽  
N. H. AlShamrani ◽  
◽  
Keyword(s):  
Lyapunov Functions ◽  
Global Solutions ◽  
Dual Infection ◽  
Steady States ◽  
Infection Model ◽  
Well Posedness ◽  
Pde Model ◽  
Existence And Stability ◽  
Infected Cells ◽  
Theoretical Results

<abstract><p>In the literature, several HTLV-I and HIV single infections models with spatial dependence have been developed and analyzed. However, modeling HTLV/HIV dual infection with diffusion has not been studied. In this work we derive and investigate a PDE model that describes the dynamics of HTLV/HIV dual infection taking into account the mobility of viruses and cells. The model includes the effect of Cytotoxic T lymphocytes (CTLs) immunity. Although HTLV-I and HIV primarily target the same host, CD$ 4^{+} $T cells, via infected-to-cell (ITC) contact, however the HIV can also be transmitted through free-to-cell (FTC) contact. Moreover, HTLV-I has a vertical transmission through mitosis of active HTLV-infected cells. The well-posedness of solutions, including the existence of global solutions and the boundedness, is justified. We derive eight threshold parameters which govern the existence and stability of the eight steady states of the model. We study the global stability of all steady states based on the construction of suitable Lyapunov functions and usage of Lyapunov-LaSalle asymptotic stability theorem. Lastly, numerical simulations are carried out in order to verify the validity of our theoretical results.</p></abstract>

ON THE DYNAMICS MALARIA-DYSENTERY CO-INFECTION MODEL

2020 ◽  
Vol 28 (02) ◽  
pp. 453-474 ◽  
Author(s):  
KAZEEM OARE OKOSUN
Keyword(s):  
Control Measures ◽  
Single Infection ◽  
Infection Model ◽  
Policy Makers ◽  
Effective Prevention ◽  
Dynamic Relationship ◽  
Increased Risk ◽  
Treatment Measures ◽  
Existence And Stability ◽  
The Impact

In this paper, a mathematical model for malaria-dysentery co-infection was formulated in order to study and examine its dynamic relationship in the presence of malaria and dysentery preventive and treatment measures. First, analysis of the single infection steady states was done and then the basic reproduction number was obtained. Furthermore, investigation into the existence and stability of equilibria carried out. The single infection models were found to exhibit the possibility of backward bifurcation. Thereafter, the impact of malaria on the dynamics of dysentery is further investigated. Second, incorporating time-dependent controls, using Pontryagin’s Maximum Principle, the necessary conditions for the optimal control of the disease was derived. It is found that malaria infection may be associated with an increased risk of dysentery. Also, that dysentery infection may be associated with an increased risk for malaria. Therefore, to effectively control malaria, the malaria intervention strategies by policy makers must at the same time it also includes effective prevention and control measures for dysentery. Policy makers should take efforts on preventive strategies in combating dysentery and malaria.

scholarly journals Combined Cytolytic Effects of a Vaccinia Virus Encoding a Single Chain Trimer of MHC-I with a Tax-Epitope and Tax-Specific CTLs on HTLV-I-Infected Cells in a Rat Model

2014 ◽  
Vol 2014 ◽  
pp. 1-13
Author(s):  
Takashi Ohashi ◽  
Takafumi Nakamura ◽  
Minoru Kidokoro ◽  
Xianfeng Zhang ◽  
Hisatoshi Shida
Keyword(s):  
T Cell ◽  
Vaccinia Virus ◽  
Combined Treatment ◽  
Type I ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Single Chain ◽  
Cell Leukemia Virus Type ◽  
Specific Ctls ◽  
Infected Cells

Adult T cell leukemia (ATL) is a malignant lymphoproliferative disease caused by human T cell leukemia virus type I (HTLV-I). To develop an effective therapy against the disease, we have examined the oncolytic ability of an attenuated vaccinia virus (VV), LC16m8Δ (m8Δ), and an HTLV-I Tax-specific cytotoxic T lymphocyte (CTL) line, 4O1/C8, against an HTLV-I-infected rat T cell line, FPM1. Our results demonstrated that m8Δ was able to replicate in and lyse tumorigenic FPM1 cells but was incompetent to injure 4O1/C8 cells, suggesting the preferential cytolytic activity toward tumor cells. To further enhance the cytolysis of HTLV-I-infected cells, we modified m8Δ and obtained m8Δ/RT1AlSCTax180L, which can express a single chain trimer (SCT) of rat major histocompatibility complex class I with a Tax-epitope. Combined treatment with m8Δ/RT1AlSCTax180L and 4O1/C8 increased the cytolysis of FPM1V.EFGFP/8R cells, a CTL-resistant subclone of FPM1, compared with that using 4O1/C8 and m8Δ presenting an unrelated peptide, suggesting that the activation of 4O1/C8 by m8Δ/RT1AlSCTax180L further enhanced the killing of the tumorigenic HTLV-I-infected cells. Our results indicate that combined therapy of oncolytic VVs with SCTs and HTLV-I-specific CTLs may be effective for eradication of HTLV-I-infected cells, which evade from CTL lysis and potentially develop ATL.

scholarly journals A functional CD8+ cell assay reveals individual variation in CD8+ cell antiviral efficacy and explains differences in human T-lymphotropic virus type 1 proviral load

2005 ◽  
Vol 86 (5) ◽  
pp. 1515-1523 ◽  
Author(s):  
Becca Asquith ◽  
Angelina J. Mosley ◽  
Anna Barfield ◽  
Sara E. F. Marshall ◽  
Adrian Heaps ◽  
...  
Keyword(s):  
Virus Type ◽  
Individual Variation ◽  
Proviral Load ◽  
Ex Vivo ◽  
Type I ◽  
T Lymphotropic Virus ◽  
Viral Burden ◽  
Infected Cells ◽  
Cd8 Cell ◽  
The Impact

The CD8+ lymphocyte response is a main component of host immunity, yet it is difficult to quantify its contribution to the control of persistent viruses. Consequently, it remains controversial as to whether CD8+ cells have a biologically significant impact on viral burden and disease progression in infections such as human immunodeficiency virus-1 and human T-lymphotropic virus type I (HTLV-I). Experiments to ascertain the impact of CD8+ cells on viral burden based on CD8+ cell frequency or specificity alone give inconsistent results. Here, an alternative approach was developed that directly quantifies the impact of CD8+ lymphocytes on HTLV-I proviral burden by measuring the rate at which HTLV-I-infected CD4+ cells were cleared by autologous CD8+ cells ex vivo. It was demonstrated that CD8+ cells reduced the lifespan of infected CD4+ cells to 1 day, considerably shorter than the 30 day lifespan of uninfected cells in vivo. Furthermore, it was shown that HTLV-I-infected individuals vary considerably in the rate at which their CD8+ cells clear infected cells, and that this was a significant predictor of their HTLV-I proviral load. Forty to 50 % of between-individual variation in HTLV-I proviral load was explained by variation in the rate at which CD8+ cells cleared infected cells. This novel approach demonstrates that CD8+ cells are a major determinant of HTLV-I proviral load. This assay is applicable to quantifying the CD8+ cell response to other viruses and malignancies and may be of particular importance in assessing vaccines.

scholarly journals Stability of a Discrete-Time Pathogen Infection Model with Adaptive Immune Response

2020 ◽  
Vol 2020 ◽  
pp. 1-26
Author(s):  
M. A. Alshaikh ◽  
A. M. Elaiw
Keyword(s):  
Global Stability ◽  
Discrete Time ◽  
Adaptive Immune Response ◽  
Steady States ◽  
Infection Model ◽  
Continuous Time Model ◽  
Time Model ◽  
Adaptive Immune ◽  
Existence And Stability ◽  
Infected Cells

This paper studies the global stability of a discrete-time pathogen dynamic model with both cell-mediated and antibody immune responses. Both latently and actively infected cells are incorporated into the model. We discretize the continuous-time model by using the nonstandard finite difference (NSFD) method. We establish that NSFD preserves the nonnegativity and boundedness of the solutions of the model. We derive four threshold parameters which govern the existence and stability of the steady states. We establish by using the Lyapunov method, the global stability of the five steady states of the model. We illustrate our theoretical results by using numerical simulations.

scholarly journals Transcriptome Analysis of Atlantic Salmon (Salmo salar) Skin in Response to Sea Lice and Infectious Salmon Anemia Virus Co-Infection Under Different Experimental Functional Diets

2022 ◽  
Vol 12 ◽  
Author(s):  
Wenlong Cai ◽  
Surendra Kumar ◽  
Umasuthan Navaneethaiyer ◽  
Albert Caballero-Solares ◽  
Laura A. Carvalho ◽  
...  
Keyword(s):  
Atlantic Salmon ◽  
Salmo Salar ◽  
Sea Lice ◽  
Single Infection ◽  
Type I ◽  
Infectious Salmon Anemia Virus ◽  
Infectious Salmon Anemia ◽  
Salmon Anemia Virus ◽  
Anemia Virus ◽  
The Impact

Sea lice (Lepeophtheirus salmonis) are ectoparasitic copepods that cause significant economic loss in marine salmoniculture. In commercial salmon farms, infestation with sea lice can enhance susceptibility to other significant pathogens, such as the highly contagious infectious salmon anemia virus (ISAv). In this study, transcriptomic analysis was used to evaluate the impact of four experimental functional feeds (i.e. 0.3% EPA/DHA+high-ω6, 0.3% EPA/DHA+high-ω6+immunostimulant (IS), 1% EPA/DHA+high-ω6, and 1% EPA/DHA+high-ω3) on Atlantic salmon (Salmo salar) during a single infection with sea lice (L. salmonis) and a co-infection with sea lice and ISAv. The overall objectives were to compare the transcriptomic profiles of skin between lice infection alone with co-infection groups and assess differences in gene expression response among animals with different experimental diets. Atlantic salmon smolts were challenged with L. salmonis following a 28-day feeding trial. Fish were then challenged with ISAv at 18 days post-sea lice infection (dpi), and maintained on individual diets, to establish a co-infection model. Skin tissues sampled at 33 dpi were subjected to RNA-seq analysis. The co-infection’s overall survival rates were between 37%-50%, while no mortality was observed in the single infection with lice. With regard to the infection status, 756 and 1303 consensus differentially expressed genes (DEGs) among the four diets were identified in “lice infection vs. pre-infection” and “co-infection vs. pre-infection” groups, respectively, that were shared between the four experimental diets. The co-infection groups (co-infection vs. pre-infection) included up-regulated genes associated with glycolysis, the interferon pathway, complement cascade activity, and heat shock protein family, while the down-regulated genes were related to antigen presentation and processing, T-cell activation, collagen formation, and extracellular matrix. Pathway enrichment analysis conducted between infected groups (lice infection vs. co-infection) resulted in several immune-related significant GO terms and pathways unique to this group, such as “autophagosome”, “cytosolic DNA-sensing pathway” and “response to type I interferons”. Understanding how experimental functional feeds can impact the host response and the trajectory of co-infections will be an essential step in identifying efficacious intervention strategies that account for the complexities of disease in open cage culture.

scholarly journals SARS-CoV-2 suppresses IFNβ production mediated by NSP1, 5, 6, 15, ORF6 and ORF7b but does not suppress the effects of added interferon

2021 ◽  
Vol 17 (8) ◽  
pp. e1009800
Author(s):  
Maya Shemesh ◽  
Turgut E. Aktepe ◽  
Joshua M. Deerain ◽  
Julie L. McAuley ◽  
Michelle D. Audsley ◽  
...  
Keyword(s):  
Type I Interferons ◽  
Type I ◽  
Mrna Levels ◽  
Interferon Stimulated Genes ◽  
Mild Disease ◽  
Major Player ◽  
Infected Cells ◽  
Type Iii Ifn ◽  
The Impact ◽  
Six Genes

Type I Interferons (IFN-Is) are a family of cytokines which play a major role in inhibiting viral infection. Resultantly, many viruses have evolved mechanisms in which to evade the IFN-I response. Here we tested the impact of expression of 27 different SARS-CoV-2 genes in relation to their effect on IFN production and activity using three independent experimental methods. We identified six gene products; NSP6, ORF6, ORF7b, NSP1, NSP5 and NSP15, which strongly (>10-fold) blocked MAVS-induced (but not TRIF-induced) IFNβ production. Expression of the first three of these SARS-CoV-2 genes specifically blocked MAVS-induced IFNβ-promoter activity, whereas all six genes induced a collapse in IFNβ mRNA levels, corresponding with suppressed IFNβ protein secretion. Five of these six genes furthermore suppressed MAVS-induced activation of IFNλs, however with no effect on IFNα or IFNγ production. In sharp contrast, SARS-CoV-2 infected cells remained extremely sensitive to anti-viral activity exerted by added IFN-Is. None of the SARS-CoV-2 genes were able to block IFN-I signaling, as demonstrated by robust activation of Interferon Stimulated Genes (ISGs) by added interferon. This, despite the reduced levels of STAT1 and phospho-STAT1, was likely caused by broad translation inhibition mediated by NSP1. Finally, we found that a truncated ORF7b variant that has arisen from a mutant SARS-CoV-2 strain harboring a 382-nucleotide deletion associating with mild disease (Δ382 strain identified in Singapore & Taiwan in 2020) lost its ability to suppress type I and type III IFN production. In summary, our findings support a multi-gene process in which SARS-CoV-2 blocks IFN-production, with ORF7b as a major player, presumably facilitating evasion of host detection during early infection. However, SARS-CoV-2 fails to suppress IFN-I signaling thus providing an opportunity to exploit IFN-Is as potential therapeutic antiviral drugs.

scholarly journals Stability of an HTLV-HIV coinfection model with multiple delays and CTL-mediated immunity

2021 ◽  
Vol 2021 (1) ◽  
Author(s):  
N. H. AlShamrani
Keyword(s):  
Time Delays ◽  
Mitotic Division ◽  
Steady States ◽  
Multiple Delays ◽  
Multiple Time ◽  
Type I ◽  
T Lymphotropic Virus ◽  
Fundamental Properties ◽  
Hiv Coinfection ◽  
Infected Cells

AbstractIn the literature, several mathematical models have been formulated and developed to describe the within-host dynamics of either human immunodeficiency virus (HIV) or human T-lymphotropic virus type I (HTLV-I) monoinfections. In this paper, we formulate and analyze a novel within-host dynamics model of HTLV-HIV coinfection taking into consideration the response of cytotoxic T lymphocytes (CTLs). The uninfected $\mathrm{CD} 4^{+}\mathrm{T}$ CD 4 + T cells can be infected via HIV by two mechanisms, free-to-cell and infected-to-cell. On the other hand, the HTLV-I has two modes for transmission, (i) horizontal, via direct infected-to-cell touch, and (ii) vertical, by mitotic division of active HTLV-infected cells. It is well known that the intracellular time delays play an important role in within-host virus dynamics. In this work, we consider six types of distributed-time delays. We investigate the fundamental properties of solutions. Then, we calculate the steady states of the model in terms of threshold parameters. Moreover, we study the global stability of the steady states by using the Lyapunov method. We conduct numerical simulations to illustrate and support our theoretical results. In addition, we discuss the effect of multiple time delays on stability of the steady states of the system.

scholarly journals Epitope targeting and viral inoculum are determinants of Nef-mediated immune evasion of HIV-1 from cytotoxic T lymphocytes

Blood ◽  
2012 ◽  
Vol 120 (1) ◽  
pp. 100-111 ◽  
Author(s):  
Diana Y. Chen ◽  
Arumugam Balamurugan ◽  
Hwee L. Ng ◽  
William G. Cumberland ◽  
Otto O. Yang
Keyword(s):  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
De Novo ◽  
Down Regulation ◽  
Specific Ctls ◽  
Cell Clearance ◽  
Infected Cells ◽  
The Impact ◽  
Hiv 1

AbstractThe impact of HIV-1 Nef-mediated HLA-I down-regulation on CD8+ cytotoxic T lymphocytes (CTLs) varies by epitope, but the determining factors have not been elucidated. In the present study, we investigated the impact of Nef on the antiviral efficiency of HIV-1–specific CTLs targeting 17 different epitopes to define properties that determine susceptibility to Nef. The impact of Nef was not correlated with the presenting HLA-I type or functional avidity of CTLs, but instead was related directly to the kinetics of infected cell clearance. Whereas Gag-specific CTLs generally were less susceptible to Nef than those targeting other proteins, this was determined by the ability to eliminate infected cells before de novo synthesis of viral proteins, which was also observed for CTLs targeting a Nef epitope. This very early clearance of infected cells depended on virus inoculum, and the required inoculum varied by epitope. These results suggest that whereas Gag-specific CTLs are more likely to recognize infected cells before Nef-mediated HLA-I down-regulation, this varies depending on the specific epitope and virus inoculum. Reduced susceptibility to Nef therefore may contribute to the overall association of Gag-specific CTL responses to better immune control if a sufficient multiplicity of infection is attained in vivo, but this property is not unique to Gag.

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