Immunogenetics and the Pathological Mechanisms of Human T-Cell Leukemia Virus Type 1- (HTLV-1-)Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP)

Mineki Saito

doi:10.1155/2010/478461

Abstract

Human T-cell leukemia virus type 1 (HTLV-1) is a replication-competent human retrovirus associated with two distinct types of disease only in a minority of infected individuals: the malignancy known as adult T-cell leukemia (ATL) and a chronic inflammatory central nervous system disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Although the factors that cause these different manifestations of HTLV-1 infection are not fully understood, accumulating evidence suggests that complex virus-host interactions play an important role in determining the risk of HAM/TSP. This review focuses on the role of the immune response in controlling or limiting viral persistence in HAM/TSP patients, and the reason why some HTLV-1-infected people develop HAM/TSP whereas the majority remains asymptomatic carriers of the virus.

Highlights

Human T-cell leukemia virus type 1 (HTLV-1) infection is of particular interest to the field of immunology as well as microbiology because HTLV-1 is never eliminated from the host in spite of vigorous cellular and humoral immune responses against the virus but causes no disease in vast majority of infected subjects
Only approximately 2%-3% develop adult T cell leukemia (ATL) [1, 2] and another 0.25%–3.8% develop chronic inflammatory diseases involving the central nervous system (HTLV-1-associated myelopathy/tropical spastic paraparesis: HAM/TSP) [3, 4], evaluation of the individual risk for developing diseases in each ACs would certainly be of considerable importance especially in HTLV-1 endemic area such as southern Japan, the Caribbean, Central and South America, the Middle East, Melanesia, and equatorial regions of Africa [5]
How does HTLV-1 persist in the individual host in spite of strong host immune response? Second, why do some HTLV-1-infected people develop consequent diseases such as ATL or HAM/TSP, whereas the majority remains asymptomatic carriers of the virus? Third, how is the inflammatory lesion in HAM/TSP initiated and maintained, and why is the inflammation in thoracic spinal cord? This review summarizes the past and recent works for HAM/TSP attempting to resolve each of these questions

Summary

Introduction

Human T-cell leukemia virus type 1 (HTLV-1) infection is of particular interest to the field of immunology as well as microbiology because HTLV-1 is never eliminated from the host in spite of vigorous cellular and humoral immune responses against the virus but causes no disease in vast majority of infected subjects (asymptomatic carriers:ACs). Previous population association study of 202 cases of HAM/TSP and 243 ACs in Kagoshima, HTLV1 endemic southern Japan, revealed that one of the major risk factors is the HTLV-1 proviral load. The median proviral load was more than ten times higher in HAM/TSP patients than in ACs, and a high proviral load was associated with an increased risk of progression to disease [24]. Further analysis to look at nonHLA host genetic factors revealed that nonHLA gene polymorphism affects the risk for developing HAM/TSP. HLA-A∗02 appears not to give protection against infection with cosmopolitan subtype A in a population in Iran [27] These findings suggest that both host genetic factors and HTLV-1 subgroup play a part in determining the risk of HAM/TSP

The Immune Response to HTLV-1

Findings

Conclusions