Transmission of Human T-Cell Lymphotropic Virus Type 1 Tax to Rabbits by tax-Only-Positive Human Cells

The human T-cell lymphrotropic virus type 1 (HTLV-1) is causally related to adult T-cell leukemia and lymphoma and the neurodegenerative diseases tropical spastic paraparesis and HTLV-1-associated myelopathy. In the United States the prevalence of infection has been estimated to range from 0.016 to 0.1% on the basis of serologic tests for antibodies to the viral structural proteins. Blood from donors positive for antibodies to HTLV-1 or HTLV-2 is not used for transfusion. However, patients with the cutaneous T-cell lymphoma mycosis fungoides (MF) are HTLV-1 and -2 seronegative yet harbor proviral sequences identical to those that encode the HTLV-1 transactivating and transforming gene product p40tax in their peripheral blood mononuclear cells (PBMCs), and they usually have antibodies to p40 tax . Moreover, a study of 250 randomly selected blood donors revealed that approximately 8% of these seronegative individuals also had HTLV-1 tax sequences and antibodies to p40 tax , while they lacked sequences and antibodies related to gag, pol ,o renv. Thus, it seemed important to determine whether the “tax-only” state can be transmitted by transfusion. To this end, PBMCs from HTLV-1 and -2 seronegative tax-only-positive MF patients or from healthy tax-only-positive blood donors were injected into adult rabbits, an established animal model for HTLV-1 infection. The PBMCs of all injected rabbits became tax sequence positive. These observations suggest that HTLV-1 tax can be transmitted by tax-only-positive mononuclear cells. The human T-cell lymphotropic virus (HTLV) type 1 (HTLV-1) is causally associated with adult T-cell leukemia and lymphoma (27) as well as with the nonneoplastic conditions tropical spastic paraparesis (5) and HTLV-associated myelopathy (22). The vast majority of patients with these diseases as well as healthy carriers of HTLV-1 have antibodies to the structural proteins of this virus. Because infection has been shown to be transmitted by transfusion (18, 21), all blood collected for this purpose has been screened for antibodies to this virus since 1988 (2). However, subsequent studies with patients with the cutaneous T-cell lymphoma mycosis fungoides (MF) revealed that the majority carry the proviral tax sequence of HTLV-1 in their peripheral blood mononuclear cells (PBMCs) and skin-infiltrating lymphocytes, while they have no antibodies to the structural proteins of the virus (14, 24). This raised the question of whether the “tax-only”-positive state may also pertain to some healthy, serologically negative blood donors. Indeed, on the basis of serologic tests for 250 randomly selected donors who presented at the New York University Medical Center blood bank, 8.6% proved to harbor proviral HTLV-1 tax in their PBMCs and also had antibodies to p40 tax , the protein encoded by this sequence (36, 39). Therefore, a study to determine whether the tax-only state could be transmitted by transfusion of tax-positive cells seemed to be indicated. It should be recalled here that HTLV-1 tax functions in the transcriptional transactivation of the HTLV-1 long terminal repeat and the transactivation of numerous cellular genes, particularly those involved in inflammation and cell proliferation, such as interleukin-1 (IL-1), IL-2, the a subunit of the IL-2 receptor, IL-6, granulocyte-macrophage colony