Variant human T-cell lymphotropic virus type 1c and adult T-cell leukemia, Australia

Abstract

Human T-cell lymphotropic virus type 1 is endemic to central Australia among Indigenous Australians. However, virologic and clinical aspects of infection remain poorly understood. No attempt has been made to control transmission to indigenous children. We report 3 fatal cases of adult T-cell leukemia/lymphoma caused by human T-cell lymphotropic virus type 1 Australo-Melanesian subtype c.

Keywords: ATLL; Australia; HTLV-1; adult T-cell leukemia/lymphoma; human T-cell lymphotropic virus type 1; indigenous Australians; molecular epidemiology; viruses.

Figure 1

CD3 (A) and CD4 (B) cells immunostained with diaminobenzidine and horseradish peroxidase in lymph node biopsy sample from patient 2 (Aus-GM). Original magnification ×40. C) Peripheral blood cells smear from adult T-lymphocytic leukemia patient 1 (Aus-NR). Tumor cells exhibiting multilobulated nuclei (or flower cells), which are mature activated CD4+ T-lymphocytes. D) Contrast-enhanced computed tomographic image of abdomen of patient 1, revealing para-aortic lymphadenopathy. E) Contrast-enhanced computed tomographic image of patient 1, showing lytic bone lesion (L-1 veretebral body) with soft tissue involvement (arrow).

Figure 2

Phylogenetic tree generated on a 1,386-bp fragment of the env gene for 30 primate T-lymphotropic virus type 1 available sequences, including the 2 sequences generated in this work (in red boldface). The lymphotropic virus type 1 strains were aligned with the DAMBE program (version 4.2.13). The final alignment was submitted to the ModelTest program (version 3.6) to select, according to the Akaike Information Criterion, the best model to apply to phylogenetic analyses. The selected model was the Tamura Nei. Bootstrap values were calculated for 1,000 replicates, and the numbers at some nodes of the tree (bootstrap values) indicate frequencies of occurrence for 100 trees. The TE4 strain from Macaca tonkeana macaques was used as an outgroup. The branch lengths are drawn to scale, and the scale bar indicates nucleotide replacements per site. Three of the 4 major HTLV-1 subtypes are shown. Subtype c corresponds to Australo-Melanesian HTLV-1c and includes the 2 env sequences (Aus-NR and Aus-GM; GenBank accession nos. KF242508 and KF242509, respectively), which were obtained from patients 1 and 2, respectively. HTLV, human T-lymphotropic virus; STLV, simian T-lymphotropic virus.