HIV-induced Cellular Factors

Health Planning &Resources Development

Investigators

Abstract

Extracellular Tat protein of HIV-1 activates virus replication in HIV-infected cells and induces a variety of host factors in uninfected cells, some of which play a critical role in the progression of HIV infection. The Arg-rich sequence of the HIV-1 Tat protein (Tat53-68) represents a key domain of the HIV-Tat protein responsible for inducing a variety of pathogenic effects including angiogenesis, enhanced virus replication, and NF-kB-mediated signal transduction pathways. This peptide, therefore, represents a potential candidate for the development of a therapeutic subunit AIDS vaccine to reduce the progression of HIV-1 infection. However, undesirable toxic effects of the Arg-rich functional domain restrict its application as a useful therapeutic agent. Selective modification of the side-chain functional groups of the Arg-rich peptide by uredo groups significantly reduced the ability of the Arg-rich peptide to induce angiogenic activity, migration of endothelial cells, and NF-kB activity in the monocytic cell line U937. While maintaining the natural peptide linkages throughout its amino acid sequence, this uredo-modification did not affect its reactivity with antibody against the full-length Tat protein. This uredo-modified Arg-rich Tat peptide could represent a critical component of a potentially safe, effective, and economical prophylactic AIDS vaccine to reduce progression of HIV infection.