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Summary To characterize susceptibility to HIV infection, we phenotyped infected tonsillar T cells by single-cell mass cytometry and created comprehensive maps to identify which subsets of CD4+ T cells support HIV fusion and productive infection. By comparing HIV-fused and HIV-infected cells through dimensionality reduction, clustering, and statistical approaches to account for viral perturbations, we identified a subset of memory CD4+ T cells that support HIV entry but not viral gene expression. These cells express high levels of CD127, the IL-7 receptor, and are believed to be long-lived lymphocytes. In HIV-infected patients, CD127-expressing cells preferentially localize to extrafollicular lymphoid regions with limited viral replication. Thus, CyTOF-based phenotyping, combined with analytical approaches to distinguish between selective infection and receptor modulation by viruses, can be used as a discovery tool. [ABSTRACT FROM AUTHOR]

Although pathogens must infect differentiated host cells that exhibit substantial diversity, documenting the consequences of infection against this heterogeneity is challenging. Single-cell mass cytometry permits deep profiling based on combinatorial expression of surface and intracellular proteins. We used this method to investigate varicella-zoster virus (VZV) infection of tonsil T cells, which mediate viral transport to skin. Our results indicate that VZV induces a continuum of changes regardless of basal phenotypic and functional T cell characteristics. Contrary to the premise that VZV selectively infects T cells with skin trafficking profiles, VZV infection altered T cell surface proteins to enhance or induce these properties. Zap70 and Akt signaling pathways that trigger such surface changes were activated in VZV-infected naive and memory cells by a T cell receptor (TCR)-independent process. Single-cell mass cytometry is likely to be broadly relevant for demonstrating how intracellular pathogens modulate differentiated cells to support pathogenesis in the natural host. [ABSTRACT FROM AUTHOR]

Objective: To examine early pregnancy (EP) testosterone (T) after ovarian stimulation and its effect on singleton pregnancy outcomes. Design: Prospective cohort study. Setting: University-based tertiary care center. Patient(s): Subfertile women who conceived with or without fertility treatment. Intervention(s): Ovarian stimulation for assisted reproduction, collection of serum total T levels in early pregnancy, and pregnancy follow-up. Main Outcome Measure(s): Rate of preterm delivery, low birth weight (LBW) (<2,500 g), and hypertensive disorders of pregnancy. Result(s): EP serum samples were measured from 266 singleton pregnancies. The mean T level among spontaneous conceptions was 74.90 ng/dL (SD 48.35 ng/dL); 103 ng/mL was the 90th percentile. Mean EP T was increased among patients who underwent ovarian stimulation compared with nonstimulated control subjects. In patients undergoing IVF, T levels in EP were linearly correlated with the number of oocytes retrieved. When pregnancy outcomes in women with normal T were compared with women with elevated T (>90th percentile), we did not see an increased risk for preterm delivery, hypertensive disorders of pregnancy, LBW infants, or cesarean delivery (odds ratio ratios 1.43, 0.38, 1.39, and 0.85, respectively). Conclusion(s): Elevations in EP T are associated with ovarian stimulation but do not appear to be associated with adverse pregnancy outcome. Further investigation to determine the etiology of increased maternal and neonatal morbidity among subfertile women is warranted. [ABSTRACT FROM AUTHOR]