Human T-lymphotropic Virus Type I Infection Research Articles

Global Dynamics of an HTLV-I and SARS-CoV-2 Co-Infection Model with Diffusion

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel respiratory virus that causes coronavirus disease 2019 (COVID-19). Symptoms of COVID-19 range from mild to severe illness. It was observed that disease progression in COVID-19 patients depends on their immune response, especially in elderly patients whose immune system suppression may put them at increased risk of infection. Human T-cell lymphotropic virus type-I (HTLV-I) attacks the CD4+ T cells (T cells) of the immune system and leads to immune dysfunction. Co-infection with HTLV-I and SARS-CoV-2 has been reported in recent studies. Modeling HTLV-I and SARS-CoV-2 co-infection can be a helpful tool to understand the in-host co-dynamics of these viruses. The aim of this study was to construct a model that characterizes the in-host dynamics of HTLV-I and SARS-CoV-2 co-infection. By considering the mobility of the viruses and cells, the model is represented by a system of partial differential equations (PDEs). The system contains two independent variables, time t and position x, and seven dependent variables for representing the densities of healthy epithelial cells (ECs), latent SARS-CoV-2-infected ECs, active SARS-CoV-2-infected ECs, SARS-CoV-2, healthy T cells, latent HTLV-I-infected T cells and active HTLV-I-infected T cells. We first studied the fundamental properties of the solutions of the system, then deduced all steady states and proved their global properties. We examined the global stability of the steady states by constructing appropriate Lyapunov functions. The analytical results were illustrated by performing numerical simulations. We discussed the effect of HTLV-I infection on COVID-19 progression. The results suggest that patients with HTLV-I have a weakened immune response; consequently, their risk of COVID-19 infection may be increased.

Global stability of HIV/HTLV co-infection model with CTL-mediated immunity

<p style='text-indent:20px;'>Mathematical modeling of human immunodeficiency virus (HIV) and human T-lymphotropic virus type Ⅰ (HTLV-I) mono-infections has received considerable attention during the last decades. These two viruses share the same way of transmission between individuals; through direct contact with certain contaminated body fluids. Therefore, a person can be co-infected with both viruses. In the present paper, we construct and analyze a new HIV/HTLV-I co-infection model under the effect of Cytotoxic T lymphocytes (CTLs) immune response. The model describes the interaction between susceptible CD<inline-formula><tex-math id="M1">\begin{document}$ 4^{+} $\end{document}</tex-math></inline-formula>T cells, silent HIV-infected cells, active HIV-infected cells, silent HTLV-infected cells, Tax-expressing (active) HTLV-infected cells, free HIV particles, HIV-specific CTLs and HTLV-specific CTLs. The HIV can spread by two routes of transmission, virus-to-cell (VTC) and cell-to-cell (CTC). Both active and silent HIV-infected cells can infect the susceptible CD<inline-formula><tex-math id="M2">\begin{document}$ 4^{+} $\end{document}</tex-math></inline-formula>T cells by CTC mechanism. On the other side, HTLV-I has only one mode of transmission via direct cell-to-cell contact. The well-posedness of the model is established by showing that the solutions of the model are nonnegative and bounded. We calculate all possible equilibria and define the key threshold parameters which govern the existence and stability of all equilibria of the model. We explore the global asymptotic stability of all equilibria by utilizing Lyapunov function and LaSalle's invariance principle. We have discussed the influence of CTL immune response on the co-infection dynamics. We have presented numerical simulations to justify the applicability and effectiveness of the theoretical results. In addition, we evaluate the effect of HTLV-I infection on the HIV dynamics and vice versa.</p>

Modeling and analysis of a within-host HIV/HTLV-I co-infection.

Human immunodeficiency virus (HIV) and human T-lymphotropic virus type I (HTLV-I) are two retroviruses that attack the {text {CD4}}^{+}T cells and impair their functions. Both HIV and HTLV-I can be transmitted between individuals through direct contact with certain body fluids from infected individuals. Therefore, a person can be co-infected with both viruses. HIV causes acquired immunodeficiency syndrome (AIDS), while HTLV-I is the causative agent for adult T-cell leukemia (ATL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Several mathematical models have been developed in the literature to describe the within-host dynamics of HIV and HTLV-I mono-infections. However, modeling a within-host dynamics of HIV/HTLV-I co-infection has not been involved. The present paper is concerned with the formulation and investigation of a new HIV/HTLV-I co-infection model under the effect of Cytotoxic T lymphocytes (CTLs) immune response. The model describes the interaction between susceptible {text {CD4}}^{+}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. The HIV can spread by virus-to-cell transmission. On the other side, HTLV-I has two modes of transmission, (i) horizontal transmission via direct cell-to-cell contact through the virological synapse, and (ii) vertical transmission through the mitotic division of Tax-expressing HTLV-infected cells. The well-posedness of the model is established by showing that the solutions of the model are nonnegative and bounded. We define a set of threshold parameters which govern the existence and stability of all equilibria of the model. We explore the global asymptotic stability of all equilibria by utilizing Lyapunov function and Lyapunov–LaSalle asymptotic stability theorem. We have presented numerical simulations to justify the applicability and effectiveness of the theoretical results. In addition, we evaluate the effect of HTLV-I infection on the HIV dynamics and vice versa.

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

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.

Mathematical analysis of an HTLV-I infection model with the mitosis of CD4+ T cells and delayed CTL immune response

In this paper, we consider an improved Human T-lymphotropic virus type I (HTLV-I) infection model with the mitosis of CD4+ T cells and delayed cytotoxic T-lymphocyte (CTL) immune response by analyzing the distributions of roots of the corresponding characteristic equations, the local stability of the infection-free equilibrium, the immunity-inactivated equilibrium, and the immunity-activated equilibrium when the CTL immune delay is zero is established. And we discuss the existence of Hopf bifurcation at the immunity-activated equilibrium. We define the immune-inactivated reproduction ratio R0 and the immune-activated reproduction ratio R1. By using Lyapunov functionals and LaSalle’s invariance principle, it is shown that if R0 < 1, the infection-free equilibrium is globally asymptotically stable; if R1 < 1 < R0, the immunity-inactivated equilibrium is globally asymptotically stable; if R1 > 1, the immunity-activated equilibrium is globally asymptotically stable when the CTL immune delay is zero. Besides, uniform persistence is obtained when R1 > 1. Numerical simulations are carried out to illustrate the theoretical results.

Analysis of a within-host HIV/HTLV-I co-infection model with immunity

Human immunodeficiency virus (HIV) and human T-lymphotropic virus type I (HTLV-I) are two retroviruses that attack the immune cells and impair their functions. Both HIV and HTLV-I can be transmitted between individuals through direct contact with certain body fluids from infected individuals. Therefore, a person can be co-infected with both viruses. HIV causes acquired immunodeficiency syndrome, while HTLV-I is the causative agent for adult T-cell leukemia and HTLV-I-associated myelopathy/tropical spastic paraparesis. Several mathematical models have been developed in the literature to describe the within-host dynamics of HIV and HTLV-I mono-infections. However, modeling a within-host dynamics of HIV/HTLV-I co-infection has not been involved. In the present paper, we are concerned to formulate and analyze a new HIV/HTLV co-infection model under the effect of Cytotoxic T lymphocytes (CTLs) immune response. The model describes the interaction between susceptible CD4+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. The HIV can spread by two routes of transmission, virus-to-cell and cell-to-cell. On the other side, HTLV-I has two modes of transmission, (i) horizontal transmission via direct cell-to-cell contact, and (ii) vertical transmission through mitotic division of Tax-expressing HTLV-infected cells. The well-posedness of the model is established by showing that the solutions of the model are nonnegative and bounded. We define a set of threshold parameters which govern the existence and stability of all equilibria of the model. We explore the global asymptotic stability of all equilibria by utilizing Lyapunov function and LaSalle's invariance principle. We have presented numerical simulations to justify the applicability and effectiveness of the theoretical results. In addition, we evaluate the effect of HTLV-I infection on the HIV dynamics and vice versa.

Human T-lymphotropic virus type I and breastfeeding; systematic review and meta-analysis of the literature

Background: The human T-cell lymphotropic virus type-I (HTLV-I) is the first identified pathogenic human retrovirus. Breastfeeding has been reported to be the predominant route of vertical transmission of HTLV-I. The objective of this systematic review was to pool and evaluate the data on the transmission of HTLV-I with different infant-feeding practices on children born to HTLV-I-positive mothers. We conducted a systematic review of comparison of HTLV-I transmission risk to breastfed and bottle-fed babies. Methods: We searched the following databases: MEDLINE, SID, Magiran, and Cochrane Library. The search strategy was limited to articles in English. Initial screening identified 254 citations; of these, 96 potentially relevant articles were identified. After reviewing the 96 full-text articles in detail, 7 reports met the inclusion criteria for this review. Results: Pooled odds ratio (OR) and risk difference (RD) of HTLV-I transmission in the breastfed group compared to the bottle-fed infants were [OR = 3.48, 95% confidence interval (CI): 1.58-7.64, P = 0.0020, Cochran's Q = 27.7, P = 0.0010, and I2 = 67.5%] and (RD = 17.1%, 95% CI: 7.5%-26.7%, P < 0.0001, Cochran's Q = 106, P < 0.0001, and I2 = 91.5%). So, we have evidence to support that exclusive breast feeding more than 6 months in comparison to bottle feeding highly increases transmission rate of HTLV-I infection. We have also enough evidence to support that exclusive breast feeding up to 6 months compared to bottle feeding does not increase transmission rate of HTLV-I infection (pooled OR = 0.912, CI: 0.45-1.80; OR: 3.83, CI: 1.80-8.10, respectively). Conclusion: The current meta-analysis showed that short period (less than 6 months) of breastfeeding did not increase risk of HTLV-I infection transmission from mother to child among breastfeeders and more than 6 months of breastfeeding significantly increased the risk of HTLV-I infection. However, our meta-analysis shows that refraining from breastfeeding can decrease the risk of vertical HTLV-I transmission.

Brief Report: Attenuated Effectiveness of Tumor Necrosis Factor Inhibitors for Anti-Human T Lymphotropic Virus Type I Antibody-Positive Rheumatoid Arthritis.

To evaluate the effectiveness of tumor necrosis factor (TNF) inhibitors for the treatment of human T lymphotropic virus type I (HTLV-I)-positive patients with rheumatoid arthritis (RA) in an area endemic for HTLV-I infection. We conducted an observational study of 585 RA patients in whom TNF inhibitors were newly introduced as a first biologic disease-modifying antirheumatic drug in an area in southwestern Japan that is endemic for HTLV-I infection. Fifty patients (8.5%) were anti-HTLV-I antibody-positive. The ages of the patients in this group were significantly higher at entry compared with the ages of patients who were anti-HTLV-I antibody-negative (n = 535). The median Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR) was 5.21. Among the total group of patients, 82% were anti-citrullinated protein antibody (ACPA)-positive. The persistence rate of TNF inhibitors at 24 weeks was 89%. The median DAS28-ESR was significantly decreased at 24 weeks in each group. The European League Against Rheumatism (EULAR) response rate was significantly better in the anti-HTLV-I antibody-negative patients (P = 0.0277). Multiple regression analysis demonstrated that anti-HTLV-I antibody status was significantly associated with the EULAR response rate and change in the DAS28-ESR and was prominent especially in the ACPA-negative subjects. No patients developed adult T cell leukemia/lymphoma (ATL) or HTLV-I-associated myelopathy (HAM) during the 24-week treatment period. The efficacy of TNF inhibitors may be attenuated in anti-HTLV-I antibody-positive patients with RA. ATL and HAM did not develop when TNF inhibitors were used for 24 weeks, but the long-term risk is not known.

Utilizing multiple pathway cross-talk networks reveals hub pathways in primary mediastinal B-cell lymphoma.

The objective of this paper was to reveal hub pathways in primary mediastinal B-cell lymphoma (PMBL) based on multiple pathway crosstalk networks (PCNs) and give insight for its pathological mechanism. Based on gene expression data, pathway data and protein-protein interaction data, background PCN (BPCN) and tumor PCN (TPCN) of PMBL were constructed. The rank product algorithm was implemented to identify hub pathways of BPCN and TPCN. Finally, topological properties (degree, closeness, betweenness, and transitivity) of hub pathways were analyzed. For BPCN, there were three hundred nodes and 42,239 edges, and the pathway pairs had great overlaps. TPCN was composed of 281 nodes and 12,700 cross-talks. A total of five hub pathways were identified, nonalcoholic fatty liver disease (NAFLD), tuberculosis, human T-lymphotropic virus type-I (HTLV-I) infection, hepatitis B, and Epstein-Barr virus infection. The topological properties for them were different from each other, further between PMBL and normal controls. We have identified five hub pathways for PMBL, such as NAFLD, HTLV-I infection, and Hepatitis B, which might be potential biomarkers for target therapy for PMBL.

Interactions between inflammatory gene polymorphisms and HTLV-I infection for total death, incidence of cancer, and atherosclerosis-related diseases among the Japanese population.

BackgroundAn increased risk of total death owing to human T-lymphotropic virus type-I (HTLV-I) infection has been reported. However, its etiology and protective factors are unclear. Various studies reported fluctuations in immune-inflammatory status among HTLV-I carriers. We conducted a matched cohort study among the general population in an HTLV-I-endemic region of Japan to investigate the interaction between inflammatory gene polymorphisms and HTLV-I infection for total death, incidence of cancer, and atherosclerosis-related diseases.MethodWe selected 2180 sub-cohort subjects aged 35–69 years from the cohort population, after matching for age, sex, and region with HTLV-I seropositives. They were followed up for a maximum of 10 years. Inflammatory gene polymorphisms were selected from TNF-α, IL-10, and NF-κB1. A Cox proportional hazard model was used to estimate the hazard ratio (HR) and the interaction between gene polymorphisms and HTLV-I for risk of total death and incidence of cancer and atherosclerosis-related diseases.ResultsHTLV-I seropositivity rate was 6.4% in the cohort population. The interaction between TNF-α 1031T/C and HTLV-I for atherosclerosis-related disease incidence was statistically significant (p = 0.020). No significant interaction was observed between IL-10 819T/C or NF-κB1 94ATTG ins/del and HTLV-I. An increased HR for total death was observed in the Amami island region, after adjustment of various factors with gene polymorphisms (HR 3.03; 95% confidence interval, 1.18–7.77).ConclusionThe present study found the interaction between TNF-α 1031T/C and HTLV-I to be a risk factor for atherosclerosis-related disease. Further follow-up is warranted to investigate protective factors against developing diseases among susceptible HTLV-I carriers.

Association between HLA-DRB1*01 and HLA-Cw*08 and outcome following HTLV-I infection.

Human T cell lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is an inflammatory disease which occurs in less than 2% of HTLV-I -infected individuals. High proviral load, high HTLV-I-specific CD8+ cytotoxic T lymphocyte frequency (CTL) and host genetic factors such as HLA all appear to be associated with HTLV-I infection. Previous studies have shown that HLA-DRB1*01 increases the risk of HAM/TSP in Japanese HTLV-I infected individuals. To investigate the association between HLA class II DRB1 alleles and HLA class I alleles (HLA-Cw*08, B54, A*02 and A-30) in HTLV-I infected individuals in Mashhad. Here we determined the frequency of HLA class II DRB1, using INNO-LIPA reverse hybridization line probe assay, and HLA class I alleles (HLA-Cw*08,B54, A*02 and A-30) by PCR-SSCP method in healthy controls, HAM/TSP patients and HTLV-I infected individuals born and resident in Mashhad. The frequency of HLA-DRB1*01 alleles in this population was different from other areas of Iran. The frequency of HLA-DRB1*01 was significantly increased in HAM/TSP patients compared with carriers (p 0.028; OR=9.4). The frequency of HLA-Cw*08 was also significantly increased in HAM/TSP patients compared with controls (p=0.03; OR=13.5). Our results may suggest that possession of HLA-DRB1*01 increases the risk of HAM/TSP in HTLV-I-infected individuals and HLA-Cw*08 correlates with low CTL immune response in HAM/TSP patients.

Tumor necrosis factor alpha inhibitors have no effect on a human T-lymphotropic virus type-I (HTLV-I)-infected cell line from patients with HTLV-I-associated myelopathy

BackgroundWhile tumor necrosis factor alpha (TNF-α) inhibitors (TNFi) and other biologics are very effective against autoimmune diseases, they can also cause infectious diseases. Therefore, it is important to clarify whether the TNFi sometimes used to treat patients with rheumatoid arthritis (RA) complicated with human T-lymphotropic virus type-I (HTLV-I) infection have the unintended side effect of promoting HTLV-I proliferation.MethodsWe used the HTLV-I-infected cell line HCT-5, derived from spinal fluid cells of a patient with HTLV-I associated myelopathy, to evaluate the production of cytokines and chemokines, TNF-α receptor (TNFR), the expression of HTLV-I associated genes, the HTLV-I proviral load (PVL), the expression of HTLV-I structural protein, and apoptosis. We used Jurkat cells as a control.ResultsSupernatants of HCT-5 showed time-dependent elevations of IL-6, RANTES and ICAM-1. HCT-5 supernatants treated with infliximab, adalimumab, etanercept (ETN), golimumab and certolizumab pegol showed no significant differences in the levels of these molecules compared to the control. Neither TNFR1 nor TNFR2 expression was altered by any TNFi treatment, relative to phosphate-buffered saline (PBS) treatment, with the exception that TNFR2 was significantly decreased and internalized in HCT-5 cells by ETN treatment. The HTLV-I associated genes Tax and HBZ and the PVL levels were not significantly changed. Immunofluorescence staining of HCT-5 for an HTLV-I-associated protein, GAG, was also not significantly different between any of the TNFi treatments and the PBS treatment. DNA ladders as an index of apoptosis were not detected. Apoptotic cells were not increased by the addition of any TNFi.ConclusionsIn vitro, TNFi did not affect the cytokine profiles, expression of associated genes and proteins, proviral load or apoptosis of HCT-5 cells. The results suggested that TNFi treatment of RA patients complicated with HTLV-I might have no effect on HTLV-I infection.

Prevalence of Sjögren's syndrome in Brazilian patients infected with human T-cell lymphotropic virus.

Human T-lymphotropic virus type I (HTLV-I) is known to be associated with neoplastic and neurodegenerative changes, and it is believed to be associated with various systemic inflammatory diseases, including Sjögren's syndrome (SS). Although HTLV-I infection is endemic in Brazil, there is no information regarding the association between HTLV-I infection and SS in the Brazilian population. The objective of this study was to determine the prevalence of SS in HTLV-I-infected individuals and the prevalence of HTLV-I infection in individuals diagnosed with SS. Serology for HTLV-I was performed in 50 patients presenting with complaints consistent with SS (the SS group). The HTLV-I group comprised 129 HTLV-I-infected patients who were screened for SS. None of the patients in the SS group tested positive for HTLV-I. Of the 129 patients in the HTLV-I group, 46 (35.7%) had xerostomia, 18 (13.95%) had xerophthalmia, eight (6.2%) had hyposalivation, two (1.55%) showed impaired tear secretion, and one (0.77%) was positive for autoantibodies (anti-SSB). In addition, six underwent minor salivary gland biopsy, and the histopathological findings were consistent with SS. Only two (1.55%) met the diagnostic criteria for SS. The prevalence of SS was found to be three times as high in HTLV-I-infected individuals as it was in those without HTLV-I infection. However, given the small number of HTLV-seropositive patients with SS, it is impossible to state that HTLV acts as an immune-activating pathogen for SS.

Seroepidemiology of human T-cell lymphotropic virus type-I in blood donors of Northeastern Iran, Sabzevar.

Background and Objectives:Human T-cell lymphotropic virus type-I (HTLV-I) infection is considered as a public health challenge in endemic areas. The virus is associated with severe diseases, such as adult T-cell leukemia/lymphoma, and HTLV-I-associated myelopathy/tropical spastic paraparesis. One of the major routes of the HTLV-I transmission includes blood transfusion. Sabzevar is located in the endemic region of HTLV-I infection. The aim of the present study was to determine the seroprevalence of HTLV-I infection in the blood donors in Sabzevar.Materials and Methods:A total of 35,067 blood donors in Sabzevar from March 2009 to April 2012 who were screened with HTLV-I on the enzyme-linked immunosorbent assay screening test were included in this survey. Reactive samples that confirmed by western blot were considered to be seropositive cases. The required data were obtained from blood donors’ database of blood transfusion service.Results:The overall prevalence of HTLV-1 based on the positive result of western blot test was 0.14%. The seropositive donors aged 17–59 years with a mean age of 38.10 ± 11.82. The prevalence rates of HTLV-I infection in 3 years of study were 0.19%, 0.14%, and 0.09%, respectively. A significant relation between age, sex, educational level, and history of blood donation was observed with seropositivity of HTLV-I.Conclusion:The improvement of donor selection and laboratory screening caused a decline in the prevalence of infection in blood donors. Given the lower prevalence of infection in regular donors with lower age and higher educational level, more efforts should be done to attract blood donors from these populations.

Treatment With Anti–Tumor Necrosis Factor Biologic Agents in Human T Lymphotropic Virus Type I–Positive Patients With Rheumatoid Arthritis

To investigate the response to and safety of anti–tumor necrosis factor (anti-TNF) therapy in human T lymphotropic virus type I (HTLV-I)–positive patients with rheumatoid arthritis (RA). Therapeutic response was evaluated in 10 HTLV-I–positive and 20 HTLV-I–negative patients with RA (sex and age matched) at 3 months after the beginning of anti-TNF therapy using the European League Against Rheumatism improvement criteria. As secondary end points, the discontinuation rate of anti-TNF therapy and its safety, especially the development of adult T cell leukemia (ATL), were evaluated over a 2-year period. Significantly higher baseline levels of C-reactive protein (CRP) were observed in HTLV-I–positive patients than in HTLV-I–negative patients (P = 0.0003). The response rate to anti-TNF therapy was lower in HTLV-I–positive patients than in HTLV-I–negative patients. The median CRP level, erythrocyte sedimentation rate, and Disease Activity Score in 28 joints at 3 months after anti-TNF treatment in HTLV-I–positive patients were significantly higher than in HTLV-I– negative patients (P = 0.003, P = 0.03, and P = 0.003, respectively). The discontinuation rate due to insufficient response was significantly higher in HTLV-I–positive patients than in HTLV-I–negative patients (P = 0.013). During the 2-year observation period, no patients developed ATL. These data suggest that HTLV-I–positive patients with RA had higher inflammation and greater resistance to anti-TNF treatment than HTLV-I–negative patients. Further study is necessary to determine whether HTLV-I infection should be measured when anti-TNF agents are administered to patients with RA, especially in areas were HTLV-I is endemic.

HTLV-I infection: A dynamic struggle between viral persistence and host immunity

Human T-lymphotropic virus type I (HTLV-I) causes chronic infection for which there is no cure or neutralising vaccine. HTLV-I has been clinically linked to the development of adult T-cell leukaemia/lymphoma (ATL), an aggressive blood cancer, and HAM/TSP, a progressive neurological and inflammatory disease. Infected individuals typically mount a large, persistently activated CD8+ cytotoxic T-lymphocyte (CTL) response against HTLV-I-infected cells, but ultimately fail to effectively eliminate the virus. Moreover, the identification of determinants to disease manifestation has thus far been elusive.A key issue in current HTLV-I research is to better understand the dynamic interaction between persistent infection by HTLV-I and virus-specific host immunity. Recent experimental hypotheses for the persistence of HTLV-I in vivo have led to the development of mathematical models illuminating the balance between proviral latency and activation in the target cell population. We investigate the role of a constantly changing anti-viral immune environment acting in response to the effects of infected T-cell activation and subsequent viral expression. The resulting model is a four-dimensional, non-linear system of ordinary differential equations that describes the dynamic interactions among viral expression, infected target cell activation, and the HTLV-I-specific CTL response. The global dynamics of the model is established through the construction of appropriate Lyapunov functions. Examining the particular roles of viral expression and host immunity during the chronic phase of HTLV-I infection offers important insights regarding the evolution of viral persistence and proposes a hypothesis for pathogenesis.

Dermatological manifestations of individuals infected with human T cell lymphotropic virus type I (HTLV‐I)

Human T cell lymphotropic virus type I (HTLV-I) is associated with specific manifestations such as adult T cell lymphoma/leukemia (ATLL), HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), HTLV-I-associated uveitis, and infective dermatitis associated with HTLV-I (IDH). Although ATLL and IDH are considered specific manifestations of HTLV-I infection, several dermatological manifestations have been described in HTLV-I seropositive patients. This study was conducted to determine the prevalences of skin lesions in patients infected with HTLV-I in an area of Brazil endemic for HTLV-I infection and to compare these prevalences with those in seronegative individuals in the same region. A prevalence study was conducted between 2008 and 2010 with two groups of individuals comprising, respectively, 179 HTLV-I seropositive (positive enzyme-linked immunosorbent assay [ELISA] and positive Western blot analysis) and 193 HTLV-I seronegative individuals (ELISA-negative). The subjects were selected on a random basis and evaluated using a questionnaire to obtain epidemiological and clinical data. A physical examination was performed to verify the presence of skin lesions. Superficial mycoses were found in 54 (30.2%) seropositive subjects and in 26 (13.5%) of the seronegative group (P<0.001). Xerosis was found in 39.1% of HTLV-I infected subjects and in 9.3% of seronegative controls (P<0.001). Ichthyosis was diagnosed in nine (5.0%) HTLV-I seropositive subjects but in none of the control group (P=0.001). A diagnosis of seborrheic dermatitis was made in 43 (24.0%) HTLV-I infected subjects and in 24 (12.4%) seronegative controls (P=0.004). Furthermore, dermatological manifestations were more intense in the HTLV-I seropositive group. Several dermatological manifestations are more common and more severe in HTLV-I seropositive subjects. The presence of these manifestations in an area endemic for HTLV-I infection may provide some clues in the investigation of this infection.

Human T Lymphotropic Virus Type I (HTLV-I) is a Risk Factor for Coronary Artery Disease.

Few studies have shown the association between HTLV-I infection and coronary artery disease (CAD). HTLV-I has been detected in heart autopsies, particularly in lymphoma\leukemia cases. Mashhad and Neyshabour (Razavi Khorasan Province, Iran) are endemic regions for HTLV-I. Therefore, the present study was carried out to evaluate the impact of HTLV-I on CAD in Neyshabourian patients. 7590 patients admitted to Razavi and Imam Reza Hospitals (2007-2008) were included in this study. The seroprevalance of HTLV-I infection was determined by the ELISA method and confirmed with the PCR method. Statistical analyses were performed using the SPSS software. Out of the 7590 studied subjects, 564 patients were born and had resided in Neyshabour. The HTLV-I sero-prevalence among these subjects was 13% (n=73). 294 subjects had an abnormal angiography (CAD) and among them 43 (14.6%) were sero-positive for HTLV-I. In the remaining 227 subjects who had a normal angiography, 30 cases were HTLV-I seropositve. The PCR test was performed on 35 cases in order to confirm the presence of infection, which was positive in 31. Regarding the initial population of 294, the rate of PCR-confirmed infection was 10.54%. Conclusion : This sero-prevalence of HTLV-I in subjects with heart complications in Neyshabour was nearly 3 times more than the general population of this city (10.5 % vs 3.4%). However, the results of this study show that in addition to HTLV-I infection, there might be other co-factors leading to the development of heart complications in Neyshabour.

Human T-lymphotropic Virus Type I (HTLV-I) Proviral Load and Clinical Features in Iranian HAM/TSP Patients: Comparison of HTLV-I Proviral Load in HAM/TSP Patients.

Human T-cell lymphotropic virus type I (HTLV-I) was the first human retrovirus discovered (1), and it has been estimated that 10-20 million people worldwide are infected with HTLV-I (2). This virus is endemic in several regions of the world, such as southwestern Japan, the Caribbean basin, Central Africa, South America, the Melanesian Islands, and the Middle East (3, 4). The prevalence of HTLV-I infection in Iran (Mashhad) is estimated to be 2-3% of the entire population, and 0.7% among blood donors (5). Most of HTLV-I-infected individuals remain asymptomatic carriers (6). Whereas, small percentage of infected individuals develop the neoplastic disease adult T-cell leukemia (ATL), and the inflammatory condition HTLV-I- associated myelopathy/tropical spastic paraparesis (HAM/TSP) (7). Only 5% of HTLV-I infected people develop HAM/TSP (8). HAM/TSP results in demyelination of the spinal cord and clinical manifestations of this disease include progressive muscle weakness and hyperreflexia of the lower limbs, sensory disturbance, urinary incontinence, and impotence (9-11). These symptoms are generally slowly progressive, while patients at older ages of onset show faster progression. Women are affected more frequently than men (12, 13). The precise pathophysiology of HAM/TSP is not yet clear but, previous studies suggested that both HTLV-I subgroups, host genetic and immunological factors may be associated with the development of HAM/TSP, particularly cytokine gene polymorphisms (14, 15). Proviral load is a major determinant of outcome for chronic virus infections such as HIV-1 and 2, hepatitis B virus, and hepatitis C virus. Also recent studies have suggested the important role of proviral load in the outcome of human T-lymphotropic virus-I infection (16). In patients with HAM/TSP, significantly higher proviral loads have been observed compared to asymptomatic carriers, suggesting that active HTLV-I viral replication plays a key role in the development of this disease. A recent study has shown that a high level of Tax expression and low CD8+ anti-viral efficiency are correlated with high proviral load (PVL) and HAM/TSP development (17). In a previous study the proviral load and host genetic risk factors for development of HAM/TSP between Iranian and Japanese HTLV-I infected individuals were compared, and it was found that the median HTLV-I proviral load of Iranian HAM/TSP patients was two-fold greater in HAM/TSP patients than in healthy carriers (HCs), whereas that of Japanese HAM/TSP patients was 13-fold greater than in HCs. In addition, The HTLV-I proviral load in Iranian HCs was significantly higher than Japanese HCs. These significant differences of proviral load between two populations reflect the role of genetic factors such as the human leukocyte antigen (HLA) genotype in populations. In this study the Iranian genome DNA samples were extracted from the whole blood but Japanese samples were from the peripheral blood mononuclear cells (PBMCs). The Iranian proviral load was probably underestimated in comparison with Japanese ones (18). The aim of this study was to evaluate the proviral load and clinical manifestation of HAM/TSP among Iranian to compare with other endemic parts of the world.

Transfusion‐transmitted human T‐lymphotropic virus Type I infection in a United States military emergency whole blood transfusion recipient in Afghanistan, 2010

The United States introduced human T-lymphotropic virus Type I (HTLV-I) screening of blood donors in 1988. The US military uses freshly collected blood products for life-threatening injuries when available stored blood components in theater have been exhausted or when these components are unsuccessful for resuscitation. These donors are screened after donation by the Department of Defense (DoD) retrospective testing program. All recipients of blood collected in combat are tested according to policy soon after and at 3, 6, and 12 months after transfusion. A 31-year-old US Army soldier tested positive for HTLV-I 44 days after receipt of emergency blood transfusions for severe improvised explosive device blast injuries. One donor's unit tested HTLV-I positive on the DoD-mandated retrospective testing. Both the donor and the recipient tested reactive with enzyme immunoassay and supplemental confirmation by HTLV-I Western blot. The donor and recipient reported no major risk factors for HTLV-I. Phylogenetic analysis of HTLV-I sequences indicated Cosmopolitan subtype, Subgroup B infections. Comparison of long terminal repeat and env sequences revealed molecular genetic linkage of the viruses from the donor and recipient. This case is the first report of transfusion transmission of HTLV-I in the US military during combat operations. The emergency fresh whole blood policy enabled both the donor and the recipient to be notified of their HTLV-I infection. While difficult in combat, predonation screening of potential emergency blood donors with Food and Drug Administration-mandated infectious disease testing as stated by the DoD Health Affairs policy should be the goal of every facility engaged with emergency blood collection in theater.