Retrovirus-mediated transfer and long-term expression of HIV type 1 tat gene in murine hematopoietic tissues.

Abstract

Replication of the human immunodeficiency virus (HIV) is regulated tightly by the tat and rev genes. The tat gene of HIV is a potent trans-activator of virus gene expression. trans-Activation is mediated through the tat-responsive element (TAR). Tat also has been shown to affect transcription of cellular genes and to trans-activate other viral promoters. In transgenic animals, tat expression in skin was implicated in the development of lesions resembling Kaposi's sarcoma (KS). More recently, evidence has been presented that suggests that Tat might play a role in the maintenance of KS cells. To study the possible role(s) of Tat in pathogenesis and disease progression, we have developed a retroviral vector for the transfer of tat into murine bone marrow cells. We used this transduced bone marrow to repopulate recipient animals, which expressed the tat gene in peripheral blood 6 months after transplantation as determined by PCR amplification of first-strand cDNA. Analysis of the hematopoietic tissues of mice 6 months posttransplantation indicated persistence of the tat gene and its expression in thymus, lymph nodes, spleen, bone marrow, and peripheral blood. Although tat expression was sustained in all hematopoietic tissues, no gross abnormalities were observed. The presence of tat in all hematopoietic tissues strongly suggests transduction of stem or multipotential progenitor cells.