15th International AIDS Conference Bangkok, Thailand - July 11-16, 2004

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. A10300)

Moriuchi H, Moriuchi M
Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan

BACKGROUND: It has been shown that mammary epithelial cells can be productively infected with HIV-1; however, its relevance to mother-to-child transmission of this virus remains unknown. Breast milk contains a number of soluble factors, some of which have various influence on HIV-1 infection. This study investigated effect of TGF-[beta, a major cytokine in breast milk on HIV-1 expression in mammary epithelial cells.

METHODS: Mammary epithelial MCF-7 cells were transfected with pGL-HIV-1-LTR and its derivatives, unstimulated or stimulated with TGF-[beta (2 ng/ml), and cell lysates were subjected for luciferase assays. Nuclear extracts were prepared from MCF-7 cells unstimulated or stimulated with TGF-[beta, and gel mobility shift assays were performed with those nuclear extracts and a double-stranded oligonucleotides containing HIV-1 LTR NF-kB binding site as a probe.

RESULTS: HIV-1 LTR activity was down-regulated by TGF-[beta. A 5'-truncation of HIV-1 LTR at -163 had no effect on the TGF-[beta effect. However, TGF-[beta-mediated suppression was abrogated by site-directed mutagenesis on HIV-1 LTR NF-kappaB site, but not SP1-binding site. In gel mobility shift assays TGF-[beta treatment diminished NF-kappaB binding to HIV-1 LTR, but had little effect on SP1 binding. Discussion: Breast-feeding is a mother-to-child transmission of HIV-1; however, transmission efficiency is not high, considering the volume and duration of breast-feeding. Inhibitory effect of TGF-[beta on HIV-1 expression in mammary cells may partly explain such inefficient transmission.

040711
A10300

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