Transcriptional enhancers of replication-competent mouse C-type retroviruses are potent determinants of the distinct disease-inducing phenotypes of different viral isolates and can also strongly influence the incidence and latent period of disease induction. To study the contribution of individual protein-binding sites to viral pathogenicity, we introduced mutations into each of the known nuclear factor-binding sites in the enhancer region of the Moloney murine leukemia virus and injected viruses with these mutations into newborn NFS mice. All viruses induced disease. Viruses with mutations in both copies of the leukemia virus factor a (LVa) site, leukemia virus factor c (LVc) site, or in just the promoter proximal copy of the glucocorticoid response element (GRE) had a latent period of disease onset and disease specificity indistinguishable from that of the wild-type Moloney virus. Viruses with mutations in two or three of the GREs, in both copies of the leukemia virus factor b (LVb) site, in two of the four nuclear factor 1 (NF1) consensus motifs, or in both copies of the conserved viral core element showed a significant delay in latent period of disease induction. Strikingly, viruses with mutations in the core element induced primarily erythroleukemias, and mutations in the LVb site also resulted in a significant incidence of erythroleukemias. These and other genetic and biochemical studies suggest models for how subtle alterations in the highly conserved structure of mouse C-type retrovirus enhancers can produce a dramatic effect on disease specificity.

We observed heterogeneity in the rates of disease progression of HIV-1 disease in infected persons, on the basis of the infecting subtype. Subtype D was associated with the most rapid progression of the disease, relative to the other 3 categories of viruses in our cohort.

Vitamin A increased the risk of HIV-1 transmission. Multivitamin (B, C, and E) supplementation of breastfeeding mothers reduced child mortality and HIV-1 transmission through breastfeeding among immunologically and nutritionally compromised women. The provision of these supplements to HIV-infected lactating women should be considered.

7 P De Togn e t a / , i b~d , p 703, T. A Banks et a1 , J /n?n?uno/ 155, 1685 (1 995) 8 Mce were ~mmun~zed intrapertoneally w~th 100 &I of phosphate-buffered sane contanng 10% SRBCs (22) Ten days later, spleens were harvested, embedded In 0 C.T compound (M~les), and frozen In q u d ntrogen Frozen t~ssue sections (6 to 10 &m th~ck) were f~xed n cold acetone Endogenous per-ox~dase was q~~enched w~th 0 2% H, O, n methanol Sectons were sta~ned by f~rst ncubatng w~t h PNA-b~o t~n (Vector) and w~th rat antserum produced to IgD (Southern B~otechnology) After wash~ng, the sections were further incubated w~th strepta\/id~n conj~lgated w~th alkalne phosphatase (AP) (Zymed) and rabb~t ant~body to rat IgG conjugated w~th horse-rad~sh perox~dase (HRP) (Southern B~otechnology) Color development for bound AP and HRP was w~th an AP reacton k~t (Vector) and w~t h d~arn~nobenz-d~ne Sect~ons were then countersta~ned w~th 1 % methyl green 9 M. L Rose, M S C B~rbeck, V J Wall~s, J A Forrester. A J Daves. Nature 284, 364 (1980) 10 T

Thirty-four human immunodeficiency virus (HIV) specialists from 16 countries contributed to this project, whose primary aim was to provide guidance on the screening, diagnosis, and monitoring of bone disease in HIV-infected patients. Four clinically important questions in bone disease management were identified, and recommendations, based on literature review and expert opinion, were agreed upon. Risk of fragility fracture should be assessed primarily using the Fracture Risk Assessment Tool (FRAX), without dual-energy X-ray absorptiometry (DXA), in all HIV-infected men aged 40-49 years and HIV-infected premenopausal women aged ≥40 years. DXA should be performed in men aged ≥50 years, postmenopausal women, patients with a history of fragility fracture, patients receiving chronic glucocorticoid treatment, and patients at high risk of falls. In resource-limited settings, FRAX without bone mineral density can be substituted for DXA. Guidelines for antiretroviral therapy should be followed; adjustment should avoid tenofovir disoproxil fumarate or boosted protease inhibitors in at-risk patients. Dietary and lifestyle management strategies for high-risk patients should be employed and antiosteoporosis treatment initiated.