Ethnoepidemiology of HTLV-1 related diseases: ethnic determinants of HTLV-1 susceptibility and its worldwide dispersal

Abstract

Human T-cell lymphotropic virus type 1 is vertically transmitted in neonatal life and is causatively associated with adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in adults. Persistence of HTLV-1 in host T cells, clonal expansion of the HTLV-1 carrying T cells, and emergence of malignantly transformed T cells are in accord with the multistep model of human cancer and roles for continuous interaction between host genes and environmental factors. This article reviews two lines of HTLV-1 investigation, one regarding worldwide surveillance of HTLV-1 infection foci by serological testing and molecular analysis of HTLV-1 isolates, and the other focusing on genetics of the human leukocyte antigen (HLA) that determines the ethnic background of HTLV-1 permissiveness and susceptibility to ATL or HAM/TSP. The serological surveillance revealed transcontinental dispersal of HTLV-1 in the prehistoric era that started out of Africa, spread to Austro-Melanesia and the Asian continent, then moved to North America and through to the southern edge of South America. This was highlighted by an Andean mummy study that proved ancient migration of paleo-mongoloid HTLV-1 from Asia to South America. Phylogenetic analysis of HLA alleles provided a basis for ethnic susceptibility to HTLV-1 infection and associated diseases, both ATL and HAM/TSP. Ethnicity-based sampling of peripheral blood lymphocytes has great potential for genome-wide association studies to illuminate ethnically defined host factors for viral oncogenesis with reference to HTLV-1 and other pathogenic elements causatively associated with chronic disease and malignancies.

Figure 1

Worldwide distribution of HTLV‐1 carriers (modified from reference 14).

Figure 2

Phylogenetic relationship of HTLV‐1 isolates in the world (modified from references and 29).

Figure 3

Phylogenetic tree of human leukocyte antigen A (HLA‐A) alleles (modified from references , , and 48).

Figure 4

Distribution of human leukocyte antigen A (HLA‐A) alleles associated with worldwide HTLV‐1 carrier populations (modified from reference 40). Carib, Caribbean; SAm, South American.

Figure 5

Transcontinental dispersal of HTLV‐1 out of Africa to South America. A–E, African Blacks; F, Melanesians; G, H, Israeli Jews; I, Asian Indians; J–L, Japanese; M, Sakhalin; N–P, Amerindians; Q–S, Caribbean/South American Blacks.