Epstein-Barr Virus DNA in Parental Oral Secretions: A Potential Source of Infection for Their Young Children.

Background: A potential source of primary Epstein-Barr virus (EBV) infection for young children is parental oral secretions. If parents who identify with racial/ethnic categories other than white have a higher prevalence of oral EBV DNA, this difference could explain why their children acquire primary EBV infection at an earlier age than white children. Methods: To test this hypothesis, we recruited parents who brought their children <8 years old to routine clinic visits, and tested the parents' oral washes for EBV DNA by real-time polymerase chain reaction. Positive samples were assayed for encapsidated EBV DNA, which is potentially infectious, versus naked EBV DNA, which is not infectious. Results: Overall, 221/800 parents (28%) had EBV DNA in their oral washes. Oral EBV DNA was more prevalent in parents who identified as non-white as compared with white parents (P = .0004), and was more prevalent in male vs female parents (P = .04). The mean quantity of EBV DNA in positive samples was 5000 copies/mL. Encapsidated viral DNA comprised 40.3% of the total EBV DNA found in parental oral secretions. Conclusions: Our data support the hypothesis that parents could be a source of virus for their young children, because 28% of parents had a mean of 5000 EBV copies/mL of oral wash and 40.3% of the EBV DNA was encapsidated. The higher prevalence of EBV DNA in non-white parents could explain why their children acquire EBV at an earlier age than children of white parents.

Transplantation of solid organ recipients shedding Epstein-Barr virus DNA pre-transplant: A prospective study.

Epstein-Barr virus (EBV) poses a significant threat to patient and graft survival post-transplant. We hypothesized that recipients who shed EBV at transplant had less immunologic control of the virus and hence were more likely to have active EBV infection and disease post-transplant. To test this hypothesis, we conducted a 5-year prospective study in primary solid organ transplant recipients. We measured EBV DNA in oral washes and blood samples by quantitative PCR before transplant and periodically thereafter for up to 4 years. Pre-transplant samples were available from 98 subjects. EBV DNA was detected pre-transplant in 32 of 95 (34%) and 5 of 93 subjects (5%) in oral wash and blood, respectively. Recipients with and without detectable pre-transplant EBV DNA were not significantly different demographically and had no significant difference in patient and graft survival (P = .6 for both comparisons) or post-transplant EBV viremia-free survival (P = .8). There were no cases of EBV-related disease or post-transplant lymphoproliferative disorder (PTLD) in any of the patients with detectable EBV DNA pre-transplant. In conclusion, detectable EBV DNA pre-transplant was not associated with differences in patient/graft survival, post-transplant EBV viremia, or EBV-related diseases including PTLD.

Rb1 and Pten Co-Deletion in Osteoblast Precursor Cells Causes Rapid Lipoma Formation in Mice.

The Rb and Pten tumor suppressor genes are important regulators of bone development and both are frequently mutated in the bone cancer osteosarcoma (OS). To determine if Rb1 and Pten synergize as tumor suppressor genes for osteosarcoma, we co-deleted them in osteoprogenitor cells. Surprisingly, we observed rapid development of adipogenic but not osteosarcoma tumors in the ΔRb1/Pten mice. ΔPten solo deleted mice also developed lipoma tumors but at a much reduced frequency and later onset than those co-deleted for Rb1. Pten deletion also led to a marked increase in adipocytes in the bone marrow. To better understand the function of Pten in bone development in vivo, we conditionally deleted Pten in OSX(+) osteoprogenitor cells using OSX-Cre mice. µCT analysis revealed a significant thickening of the calvaria and an increase in trabeculae volume and number in the femur, consistent with increased bone formation in these mice. To determine if Pten and Rb1 deletion actively promotes adipogenic differentiation, we isolated calvarial cells from Pten(fl/fl) and Pten(fl/fl); Rb1(fl/fl) mice, infected them with CRE or GFP expressing adenovirus, treated with differentiation media. We observed slightly increased adipogenic, and osteogenic differentiation in the ΔPten cells. Both phenotypes were greatly increased upon Rb1/Pten co-deletion. This was accompanied by an increase in expression of genes required for adipogenesis. These data indicate that Pten deletion in osteoblast precursors is sufficient to promote frequent adipogenic, but only rare osteogenic tumors. Rb1 hetero- or homo-zygous co-deletion greatly increases the incidence and the rapidity of onset of adipogenic tumors, again, with only rare osteosarcoma tumors.