Small Nuclear RNAs Encoded by Herpesvirus saimiri Upregulate the Expression of Genes Linked to T Cell Activation in Virally Transformed T Cells

SummarySeven small nuclear RNAs of the Sm class are encoded by Herpesvirus saimiri (HVS), a γ Herpesvirus that causes aggressive T cell leukemias and lymphomas in New World primates and efficiently transforms T cells in vitro [1–4]. The Herpesvirus saimiri U RNAs (HSURs) are the most abundant viral transcripts in HVS-transformed, latently infected T cells but are not required for viral replication or transformation in vitro [5]. We have compared marmoset T cells transformed with wild-type or a mutant HVS lacking the most highly conserved HSURs, HSURs 1 and 2. Microarray and Northern analyses reveal that HSUR 1 and 2 expression correlates with significant increases in a small number of host mRNAs, including the T cell-receptor β and γ chains, the T cell and natural killer (NK) cell-surface receptors CD52 and DAP10, and intracellular proteins—SKAP55, granulysin, and NKG7—linked to T cell and NK cell activation. Upregulation of three of these transcripts was rescued after transduction of deletion-mutant-HVS-transformed cells with a lentiviral vector carrying HSURs 1 and 2. These changes indicate an unexpected role for the HSURs in regulating a remarkably defined and physiologically relevant set of host targets involved in the activation of virally transformed T cells during latency

A modelling study to evaluate the costs and effects of lowering the starting age of population breast cancer screening

\u3cp\u3eBackground Because the incidence of breast cancer increases between 45 and 50 years of age, a reconsideration is required of the current starting age (typically 50 years) for routine mammography. Our aim was to evaluate the quantitative benefits, harms, and cost-effectiveness of lowering the starting age of breast cancer screening in the Dutch general population. Methods Economic modelling with a lifelong perspective compared biennial screening for women aged 48–74 years and for women aged 46–74 years with the current Dutch screening programme, which screen women between the ages of 50 and 74 years. Tumour deaths prevented, years of life saved (YOLS), false-positive rates, radiation-induced tumours, costs and incremental cost-effectiveness ratios (ICERs) were evaluated. Results Starting the screening at 48 instead of 50 years of age led to increases in: the number of small tumours detected (4.0%), tumour deaths prevented (5.6%), false positives (9.2%), YOLS (5.6%), radiation-induced tumours (14.7%), and costs (4.1%). Starting the screening at 46 instead of 48 years of age increased the number of small tumours detected (3.3%), tumour deaths prevented (4.2%), false positives (8.8%), YOLS (3.7%), radiation-induced tumours (15.2%), and costs (4.0%). The ICER was €5600/YOLS for the 48–74 scenario and €5600/YOLS for the 46–74 scenario. Conclusions Women could benefit from lowering the starting age of screening as more breast cancer deaths would be averted. Starting regular breast cancer screening earlier is also cost-effective. As the number of additional expected harms is relatively small in both the scenarios examined, and the difference in ICERs is not large, introducing two additional screening rounds is justifiable.\u3c/p\u3