Vulnerability to APOBEC3G linked to the pathogenicity of deltaretroviruses.

Human retroviruses are derived from simian ones through cross-species transmission. These retroviruses are associated with little pathogenicity in their natural hosts, but in humans, HIV causes AIDS, and human T-cell leukemia virus type 1 (HTLV-1) induces adult T-cell leukemia-lymphoma (ATL). We analyzed the proviral sequences of HTLV-1, HTLV-2, and simian T-cell leukemia virus type 1 (STLV-1) from Japanese macaques (Macaca fuscata) and found that APOBEC3G (A3G) frequently generates G-to-A mutations in the HTLV-1 provirus, whereas such mutations are rare in the HTLV-2 and STLV-1 proviruses. Therefore, we investigated the mechanism of how HTLV-2 is resistant to human A3G (hA3G). HTLV-1, HTLV-2, and STLV-1 encode the so-called antisense proteins, HTLV-1 bZIP factor (HBZ), Antisense protein of HTLV-2 (APH-2), and STLV-1 bZIP factor (SBZ), respectively. APH-2 efficiently inhibits the deaminase activity of both hA3G and simian A3G (sA3G). HBZ and SBZ strongly suppress sA3G activity but only weakly inhibit hA3G, suggesting that HTLV-1 is incompletely adapted to humans. Unexpectedly, hA3G augments the activation of the transforming growth factor (TGF)-ß/Smad pathway by HBZ, and this activation is associated with ATL cell proliferation by up-regulating BATF3/IRF4 and MYC. In contrast, the combination of APH-2 and hA3G, or the combination of SBZ and sA3G, does not enhance the TGF-ß/Smad pathway. Thus, HTLV-1 is vulnerable to hA3G but utilizes it to promote the proliferation of infected cells via the activation of the TGF-ß/Smad pathway. Antisense factors in each virus, differently adapted to control host cellular functions through A3G, seem to dictate the pathogenesis.

Pilot study of dietary influences on mammographic density in pre- and postmenopausal Hispanic and non-Hispanic white women.

OBJECTIVE: The extent to which modifiable dietary factors may account for some of the variability demonstrated in mammographic density across ethnic groups is unknown. The purpose of this study was to provide pilot data describing the relationship between dietary variables and mammographic density in pre- and postmenopausal Hispanic and non-Hispanic white (NHW) women (N=238) ranging in age from 41 to 50 years (premenopausal only) or 56 to 70 years (postmenopausal only). DESIGN: Using a cross-sectional design, computer-assisted density assessments were performed on mammograms of both breasts and averaged for analysis. The Arizona Food Frequency Questionnaire was used to estimate dietary intake. RESULTS: Study participants were well educated and overweight, with mean mammographic densities ranging from 20.25% for postmenopausal Hispanic women to 46.94% for premenopausal NHW women. Hispanic women reported higher energy intake than NHW women, but energy-adjusted intake of other nutrients was generally comparable. There was preliminary evidence of ethnic variability in diet-mammographic density associations. Among premenopausal Hispanic women, density was inversely associated with dairy, calcium, and vitamin D intakes (P