Human T-Lymphotropic Viruses (1 and 2)

Etiology

Human T-lymphotropic viruses 1 (HTLV-1) and 2 (HTLV-2) are members of the Deltaretrovirus genus of the Retroviridae family and are single-stranded RNA viruses that encode reverse transcriptase, an RNA-dependent DNA polymerase that transcribes the single-stranded viral RNA into a double-stranded DNA copy. HTLV-1 was the first human retrovirus discovered, isolated in 1979 by the Gallo laboratory from a cutaneous T-cell lymphoma. The closely related virus HTLV-2 was subsequently identified in 1981. HTLV-1 is associated with adult T-cell leukemia/lymphoma (ATL) and HTLV-1–associated myelopathy/tropical spastic paraparesis (HAM/TSP), whereas HTLV-2 is less pathogenic and is rarely associated with leukemia or neurologic diseases.

HTLV-1 and -2 share a genome homology of approximately 65%. The genome contains gag, pol, and env genes and the pX region, which encodes nonstructural proteins. The nonstructural proteins include the Tax and Rex regulatory proteins, the novel proteins essential for virus spread (p30, p12, and p13), and the antisense-encoded HTLV-1 basic leucine zipper factor HBZ. HTLV-1 and -2 infect cells via the ubiquitous glucose transporter type or via Neuropilin-1, which serve as virus receptors. HTLV-1 and -2 can infect a variety of cells, with HTLV-1 most often found in CD4+ T cells and HTLV-2 showing a preference for CD8+ T cells. Following viral entry, reverse transcription produces a double-stranded DNA copy of the RNA genome that is transported into the nucleus and integrated into chromosomal DNA (the provirus), evading the typical mechanisms of immune surveillance and facilitating lifelong infection.

Epidemiology and Modes of Transmission

HTLV-1 infects 15-20 million persons globally. It is endemic in southwestern Japan (where > 10% of adults are seropositive), areas of the Caribbean, including Jamaica and Trinidad (≤6%), and in parts of sub-Saharan Africa (≤5%). Lower seroprevalence rates are found in South America (≤2%) and Taiwan (0.1–1%). There is microclustering with marked variability within geographic regions.

The seroprevalence of HTLV-1 and HTLV-2 in the United States in the general population is 0.01–0.03% for each virus, with higher rates with increasing age. The prevalence of HTLV-1 infection is highest in babies born in endemic areas or in persons who have had sexual contact with persons from endemic areas. The prevalence of HTLV-2 infection is highest in intravenous drug users, with a seroprevalence of 8.8–17.6% in this population.

HTLV-1 and -2 are transmitted as cell-associated viruses from mother to child and transmission through genital secretions, contaminated blood products, and intravenous drug use. Mother-to-child transmission during the intrauterine period or peripartum period is estimated to occur in less than 5% of cases but increases to approximately 20% with breastfeeding. A higher maternal HTLV-1 proviral load and prolonged breastfeeding are associated with a greater risk of mother-to-child transmission. In Japan, approximately 20–25% of children born to HTLV-1–infected mothers became infected prior to recommendations that seropositive mothers should avoid breastfeeding, with a marked reduction to 2.5% transmission following restriction of breastfeeding. HTLV-2 may also be transmitted via breastfeeding, but it has a slightly lower reported transmission rate via breast milk of approximately 14%.