Mechanisms of human T-lymphotropic virus type 1 transmission and disease

► Human T-lymphotrophic virus type-1 infects approximately 15–20 million people worldwide. ► The virus is spread through contact with bodily fluids most often from mother to child through breast milk or via blood transfusion. ► After prolonged latency periods, approximately 3–5% of HTLV-1 infected individuals will develop either adult T-cell leukemia/lymphoma, or other lymphocyte-mediated disorders. ► The genome of this complex retrovirus contains typical gag, pol, and env genes, but also unique nonstructural proteins encoded from the pX region. ► Tax and Rex regulatory and nonstructural proteins are essential for the infectivity and pathogenesis of the virus. Human T-lymphotrophic virus type-1 (HTLV-1) infects approximately 15–20 million people worldwide, with endemic areas in Japan, the Caribbean, and Africa. The virus is spread through contact with bodily fluids containing infected cells most often from mother to child through breast milk or via blood transfusion. After prolonged latency periods, approximately 3–5% of HTLV-1 infected individuals will develop either adult T-cell leukemia/lymphoma, or other lymphocyte-mediated disorders such as HTLV-1-associated myelopathy/tropical spastic paraparesis. The genome of this complex retrovirus contains typical gag, pol, and env genes, but also unique nonstructural proteins encoded from the pX region. These nonstructural genes encode the Tax and Rex regulatory proteins, as well as novel proteins essential for viral spread in vivo such as p30, p12, p13 and the antisense-encoded HTLV-1 basic leucine zipper factor (HBZ). While progress has been made in knowledge of viral determinants of cell transformation and host immune responses, host and viral determinants of HTLV-1 transmission and spread during the early phases of infection are unclear. Improvements in the molecular tools to test these viral determinants in cellular and animal models have provided new insights into the early events of HTLV-1 infection. This review will focus on studies that test HTLV-1 determinants in context to full-length infectious clones of the virus providing insights into the mechanisms of transmission and spread of HTLV-1.