Tat protein of HIV-1 stimulates growth of cells derived from Kaposi's sarcoma lesions of AIDS patients

Abstract

Kaposi's sarcoma (KS) is frequently associated with human immunodeficiency virus-1 (HIV-1) infection. Supernatants from HIV-1-infected T cells carrying the CD4 antigen promote the growth of cells derived from KS lesions of AIDS patients (AIDS-KS cells), and the HIV-1 tat gene, introduced into the germ line of mice, induces skin lesions closely resembling KS. Here we report that the tat gene product (Tat) is released from both HIV-1-acutely infected H9 cells and tat-transfected COS-1 cells. These Tat-containing supernatants specifically promote growth of AIDS-KS cells which are inhibited by anti-Tat antibodies; recombinant Tat has the same growth-promoting properties. Therefore a viral regulatory gene product can be released as a biologically active protein and directly act as a growth stimulator. These and previous data indicate that extracellular Tat could be involved in the development or progression, or both, of KS in HIV-1-infected individuals.

Classic Kaposi Sarcoma in the United States over the last two decades: A clinicopathologic and molecular study of 438 non-HIV-related Kaposi Sarcoma patients with comparison to HIV-related Kaposi Sarcoma

“…21,[31][32][33][34][35][36][37] This virus induces cytokines, which are known to play a role in the development of Classic Kaposi Sarcoma. 10,38 It is hypothesized that lymphoproliferative disorders or other malignancies might pass HHV-8 to its lytic phase, in sites of latency, 39 and 40 Although the majority of our subgroup of Classic Kaposi Sarcoma patients, representing a cross-section oflesional stage and patient gender, were positive by PCR analysis for HHV-8, one case with ample material was negative. These data are consistent with the findings of other published studies on the incidence of HHV-8 in Kaposi Sarcoma.…”

Comparative study of Tat vaccine regimens in Mauritian cynomolgus and Indian rhesus macaques: Influence of Mauritian MHC haplotypes on susceptibility/resistance to SHIV89.6P infection

“…Tat is produced early after infection [1,2] and is indispensable for viral replication, transmission, and AIDS pathogenesis [3][4][5][6]. Release of Tat from infected cells and its uptake by infected and uninfected cells is critical to the biology of the virus [5,[7][8][9][10]. In infected cells, Tat promotes viral replication or transactivates the replication of tat-defective or latent proviruses [11].…”

Long-term protection against SHIV89.6P replication in HIV-1 Tat vaccinated cynomolgus monkeys

“…In addition, Tat can modulate the expression of cytokines and cellular genes [6][7][8][9][10][11], and chemokine receptors [12][13][14][15], which are responsible for the transmission of macrophageand T-cell-tropic HIV-1 strains, respectively. In addition, the Tat protein also plays key roles in viral pathogenesis and in the pathogenesis of acquired immune deficiency syndrome (AIDS)-associated Kaposi's sarcoma [8,[16][17][18][19][20][21][22].…”