A HIV-1 Stimulating Host Factor Induced by HIV-1 Tat Protein

Abstract

Listen

Translate article

The HIV-1 Tat gene is required for virus replication and disease. Tat was reported to be released from infected cells. Recombinant soluble Tat may be taken up by many cell types and transported to the nucleus as an active transcription factor leading to upregulation of viral replication in bystander cells. However, numerous attempts to use Tat protein or Tat expressing constructs for protective immunization in non human primate model produced controversial results, leading us to ask whether the effects of Tat might be indirect and result from increased expression of secondary mediators like cytokines or growth factors. Immunization with Tat protein produces antibodies to a limited number of linear epitopes in animals and human beings, mainly located in the N-terminus of the molecule. We generated a unique prototypic monoclonal antibody TR1 that recognizes an epitope in the N-terminus of HIV1 Tat and inhibits Tat uptake by reporter cells. This antibody strongly neutralizes recombinant Tat protein in a cellular assay for the induction of a latent Tat deficient HIV-1 provirus. Expression of Tat protein in different cell types leads to the accumulation of a transactivation in culture medium. However, 1) this activity cannot be inhibited by Tat-neutralizing antibody TR1;