Abstract
Human T-cell Leukemia virus type-1 (HTLV-1) causes adult T-cell leukemia/lymphoma (ATLL), HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and other inflammatory diseases. High viral DNA burden (VL) in peripheral blood mononuclear cells is a documented risk factor for ATLL and HAM/TSP, and patients with HAM/TSP have a higher VL in cerebrospinal fluid than in peripheral blood. VL alone is not sufficient to differentiate symptomatic patients from healthy carriers, suggesting the importance of other factors, including host immune response. HTLV-1 infection is life-long; CD4-infected cells are not eradicated by the immune response because HTLV-1 inhibits the function of dendritic cells, monocytes, Natural Killer cells, and adaptive cytotoxic CD8responses. Although the majority of infected CD4T-cells adopt a resting phenotype, antigen stimulation may result in bursts of viral expression. The antigen-dependent "on-off" viral expression creates "conditional latency" that when combined with ineffective host responses precludes virus eradication. Epidemiological and clinical data suggest that the continuous attempt of the host immunity to eliminate infected cells results in chronic immune activation that can be further exacerbated by co-morbidities, resulting in the development of severe disease. We review cell and animal model studies that uncovered mechanisms used by HTLV-1 to usurp and/or counteract host immunity.
Overview
- The study focuses on the role of Human T-cell Leukemia virus type-1 (HTLV-1) in the development of adult T-cell leukemia/lymphoma (ATLL), HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and other inflammatory diseases. The study aims to understand the mechanisms used by HTLV-1 to usurp and/or counteract host immunity. The methodology used for the experiment includes a review of cell and animal model studies. The primary objective of the study is to identify the mechanisms used by HTLV-1 to evade host immunity and contribute to the development of severe disease.
Comparative Analysis & Findings
- The study compares the outcomes observed under different experimental conditions or interventions detailed in the review. The results show that HTLV-1 inhibits the function of dendritic cells, monocytes, Natural Killer cells, and adaptive cytotoxic CD8 responses, leading to conditional latency. This conditional latency precludes virus eradication when combined with ineffective host responses. The study also highlights the importance of continuous host immunity attempts to eliminate infected cells, which can result in chronic immune activation and exacerbation of co-morbidities, leading to severe disease.
Implications and Future Directions
- The study's findings have significant implications for the field of research and clinical practice. The study suggests that the continuous attempt of the host immunity to eliminate infected cells results in chronic immune activation, which can be further exacerbated by co-morbidities, leading to severe disease. The study also highlights the importance of understanding the mechanisms used by HTLV-1 to evade host immunity and contribute to the development of severe disease. Future research directions could focus on developing effective strategies to eliminate infected cells and prevent the development of severe disease.