Proliferative activity of extracellular HIV-1 Tat protein in human epithelial cells: expression profile of pathogenetically relevant genesReport as inadecuate




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BMC Microbiology

, 5:20

First Online: 27 April 2005Received: 23 December 2004Accepted: 27 April 2005

Abstract

BackgroundTat is being tested as a component of HIV vaccines. Tat activity has been mainly investigated on cells of lymphoid-hematopoietic lineages. HIV-1, however, is known to infect many different cells of both solid organs and mucosal surfaces. The activity of two-exon aa 1–101 and synthetic aa 1–86 Tat was studied on mammary and amniotic epithelial cells cultured under low serum conditions.

Resultssmall concentrations of Tat 100 ng-ml stimulated cell proliferation. Tat antibodies neutralized the mitogenic Tat activity. Changes of gene expression in Tat-treated cells were evaluated by RT-PCR and gene-array methods. Within 4 hours of treatment, exposure to Tat is followed by up-regulation of some cell cycle-associated genes transcription factors, cyclin-cdk complexes, genes of apoptotic pathways and of genes relevant to HIV pathogenesis chemokine receptors CXCR4, CCR3, chemotactic cytokines SDF-1, RANTES, SCYC1, SCYE1, IL6 family cytokines, inflammatory cytokines, factors of the TGF-beta family TGFb, BMP-1, BMP-2. Up-regulation of anti-inflammatory cytokines IL-10, IL-19, IL-20, a hallmark of other persistent viral infections, was a remarkable feature of Tat-treated epithelial cell lines.

Conclusionextracellular Tat is mitogenic for mammary and amniotic epithelial cells and stimulates the expression of genes of pathogenetic interest in HIV infection. These effects may favor virus replication and may facilitate the mother-to-child transmission of virus.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2180-5-20 contains supplementary material, which is available to authorized users.

Alessia A Bettaccini, Andreina Baj and Antonio Q Toniolo contributed equally to this work.

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Author: Alessia A Bettaccini - Andreina Baj - Roberto S Accolla - Fulvio Basolo - Antonio Q Toniolo

Source: https://link.springer.com/article/10.1186/1471-2180-5-20







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