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

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.

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Accumulation of human T-lymphotropic virus type I (HTLV-I)–infected cells in the cerebrospinal fluid during the exacerbation of HTLV-I–associated myelopathy

Journal of NeuroVirology ◽

10.1080/13550280802178538 ◽

2008 ◽

Vol 14 (5) ◽

pp. 459-463 ◽

Cited By ~ 17

Author(s):

Daisuke Hayashi ◽

Ryuji Kubota ◽

Norihiro Takenouchi ◽

Tomonori Nakamura ◽

Fujio Umehara ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Virus Type ◽

Type I ◽

T Lymphotropic Virus ◽

Infected Cells

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Inhibition of Human T-Lymphotropic Virus Type I Gene Expression by the Streptomyces-Derived Substance EM2487

Antiviral Chemistry and Chemotherapy ◽

10.1177/095632020201300304 ◽

2002 ◽

Vol 13 (3) ◽

pp. 177-183 ◽

Cited By ~ 5

Author(s):

X Wang ◽

M Okamoto ◽

M Kawamura ◽

S Izumo ◽

M Baba

Keyword(s):

Gene Expression ◽

Virus Type ◽

Mononuclear Cells ◽

Spastic Paraparesis ◽

Selective Inhibition ◽

Pcr Analysis ◽

Type I ◽

Peripheral Blood Mononuclear ◽

T Lymphotropic Virus ◽

Infected Cells

EM2487, a Streptomyces-derived substance, has previously been shown to inhibit HIV-1 replication in both acutely and chronically infected cells. In this study, we found that EM2487 was also a selective inhibitor of human T-lymphotropic virus type I (HTLV-I) replication in persistently infected cells. Its 50% effective concentrations for HTLV-I p19 antigen production were 3.6 and 1.2 μM in MT-2 and MT-4 cells, respectively. However, the compound did not reduce cell proliferation and viability at these concentrations. The 50% cytotoxic concentrations of EM2487 were 30.6 and 5.7 μM in MT-2 and MT-4 cells, respectively. The compound also displayed selective inhibition of HTLV-I production in peripheral blood mononuclear cells obtained from patients with HTLV-I-associated myelopathy/tropical spastic paraparesis. Quantitative reverse transcription PCR analysis revealed that EM2487 selectively suppressed HTLV-I mRNA synthesis in MT-2 cells in a dose-dependent fashion. However, the compound did not inhibit endogenous Tax-induced HTLV-I long terminal repeat-driven reporter gene expression. Furthermore, intracellular Tax accumulation was not suppressed in MT-2 cells exposed to EM2487. These results suggest that the inhibition occurred at the viral transcription level, but it cannot be attributed to the inhibition of the Tax function.

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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

Journal of General Virology ◽

10.1099/vir.0.80766-0 ◽

2005 ◽

Vol 86 (5) ◽

pp. 1515-1523 ◽

Cited By ~ 60

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.

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HTLV/HIV Dual Infection: Modeling and Analysis

Mathematics ◽

10.3390/math9010051 ◽

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.

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Prevention of Mother-to-Child Transmission of Human T-Lymphotropic Virus Type-I

PEDIATRICS ◽

10.1542/peds.86.1.11 ◽

1990 ◽

Vol 86 (1) ◽

pp. 11-17

Author(s):

Yoshiro Tsuji ◽

Hiroshi Doi ◽

Tooru Yamabe ◽

Tadayuki Ishimaru ◽

Tsutomu Miyamoto ◽

...

Keyword(s):

T Cell ◽

Breast Milk ◽

Virus Type ◽

Type I ◽

T Lymphotropic Virus ◽

Adult T Cell Leukemia ◽

Human T Cell ◽

Infected Cells ◽

Mother To Child ◽

Nagasaki Prefecture

Human T-cell lymphotropic virus type I (HTLV-I), an etiologic human retrovirus of adult T-cell leukemia/lymphoma (ATLL), causes approximately 60 new cases of ATLL each year in Nagasaki Prefecture; essentially all cases are fatal, and they account for approximately 0.5% of total deaths in the area. The estimated life risk for an HTLV-I carrier to develop ATLL is approximately 5%. The major transmission pathway of HTLV-I peculiarly endemic in the Nagasaki Prefecture was studied. The prevalence of HTLV-I infection in children of carrier mothers (21%) was significantly higher than that in children in the general population in the area (1%), and more than 85% of mothers of carrier children were carriers. The breast milk of carrier mothers contained HTLV-I-infected cells and was infectious for marmoset via oral administration. A retrospective survey of children of carrier mothers showed that the prevalence of carrier children of carrier mothers was 17 (39%) of 44 and 0 (0%) of 10 when they were given breast milk only or formula only, respectively. These data provide a powerful basis for devising an intervention measure to block the endemic cycle of HTLV-I; ie, if carrier mothers refrain from breast-feeding, the incidence of ATLL will be significantly reduced some 50 years later.

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Transcriptional activation of human TR3/nur77 gene expression by human T-lymphotropic virus type I Tax protein through two AP-1-like elements

Journal of General Virology ◽

10.1099/0022-1317-80-12-3073 ◽

1999 ◽

Vol 80 (12) ◽

pp. 3073-3081 ◽

Cited By ~ 17

Author(s):

Xiangdong Liu ◽

Xiaolin Chen ◽

Vladimir Zachar ◽

Chawnshang Chang ◽

Peter Ebbesen

Keyword(s):

Transcription Factor ◽

Virus Type ◽

Transcriptional Activation ◽

Gene Deletion ◽

Type I ◽

Transcription Start ◽

T Lymphotropic Virus ◽

Tax Protein ◽

Infected Cells ◽

Mutation Analyses

The Tax transactivator of human T-lymphotropic virus type I (HTLV-I) is capable of inducing expression of the human immediate-early TR3/nur77 gene. Deletion and mutation analyses of the TR3/nur77 promoter demonstrated that multiple transcription elements in the 121 bp sequence proximal to the transcription start site are required for full Tax transactivation. Mutations of CArG-like, Ets and RCE motifs in this region severely decreased Tax transactivation. Mutation of either of the two identical AP-1-like elements (NAP 1 and 2) immediately upstream of the TATA box caused around 80% reduction of Tax transactivation. Mutation of both NAP elements blocked Tax-mediated activation totally. These two NAP elements could confer Tax-responsiveness on a heterologous basal promoter. Furthermore, the specific NAP-binding complex was only observed in HTLV-I-infected cells. Formation of this specific NAP-binding complex was correlated directly with Tax expression, as demonstrated in JPX-9 cells upon induction of Tax expression. The specific NAP binding could be competed for by consensus AP-1 and CREB elements, indicating that the NAP-binding proteins probably belong to the AP-1 and CREB/ATF transcription factor families. Supershift analysis with antibodies to both the AP-1 and CREB/ATF transcription factor families revealed that only anti-JunD antibody could partially shift this NAP-binding complex, indicating that JunD is a component of the NAP complex. This work suggests that JunD is involved in Tax-regulated TR3/nur77 expression.

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Synchronization Analysis of a Class of Neural Networks with Multiple Time Delays

Journal of Mathematics ◽

10.1155/2021/5573619 ◽

2021 ◽

Vol 2021 ◽

pp. 1-9

Author(s):

Changyou Wang ◽

Qiang Yang ◽

Tao Jiang ◽

Nan Li

Keyword(s):

Neural Network ◽

Neural Networks ◽

Lyapunov Function ◽

Differential Inequality ◽

Time Delays ◽

Multiple Delays ◽

Multiple Time ◽

Multiple Time Delays ◽

Delay Differential ◽

Delay Differential Inequality

In this paper, we study the synchronization of a new fractional-order neural network with multiple delays. Based on the control theory of linear systems with multiple delays, we get the controller to analyse the synchronization of the system. In addition, a suitable Lyapunov function is constructed by using the theory of delay differential inequality, and some criteria ensuring the synchronization of delay fractional neural networks with Caputo derivatives are obtained. Finally, the accuracy of the method is verified by a numerical example.

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A Fractional-Order Model for Zika Virus Infection with Multiple Delays

Complexity ◽

10.1155/2019/4178073 ◽

2019 ◽

Vol 2019 ◽

pp. 1-20 ◽

Cited By ~ 3

Author(s):

R. Rakkiyappan ◽

V. Preethi Latha ◽

Fathalla A. Rihan

Keyword(s):

Hopf Bifurcation ◽

Virus Infection ◽

Numerical Simulations ◽

Fractional Order ◽

Zika Virus ◽

Epidemic Model ◽

Time Delays ◽

Multiple Delays ◽

Multiple Time ◽

Zika Virus Infection

Time delays and fractional order play a vital role in biological systems with memory. In this paper, we propose an epidemic model for Zika virus infection using delay differential equations with fractional order. Multiple time delays are incorporated in the model to consider the latency of the infection in a vector and the latency of the infection in the infected host. We investigate the necessary and sufficient conditions for stability of the steady states and Hopf bifurcation with respect to three time delays τ1, τ2, and τ3. The model undergoes a Hopf bifurcation at the threshold parameters τ1∗, τ2∗, and τ3∗. Some numerical simulations are given to show the effectiveness of obtained results. The numerical simulations confirm that combination of fractional order and time delays in the epidemic model effectively enriches the dynamics and strengthens the stability condition of the model.

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