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HIV-1 infects immature dendritic cells (iDCs), but infection is inefficient compared with activated CD4+ T cells and only involves a small subset of iDCs. We analyzed whether this could be attributed to specific cellular restrictions during the viral life cycle. To study env-independent restriction to HIV-1 infection, we used a single-round infection assay with HIV-1 pseudotyped with vesicular stomatitis virus G protein (HIV-VSVG). Small interfering RNA–mediated depletion of APOBEC3G/3F (A3G/3F), but not TRIM5α, enhanced HIV-1 infection of iDCs, indicating that A3G/3F controls the sensitivity of iDCs to HIV-1 infection. Furthermore, sequences of HIV reverse transcripts revealed G-to-A hypermutation of HIV genomes during iDC infection, demonstrating A3G/3F cytidine deaminase activity in iDCs. When we separated the fraction of iDCs that was susceptible to HIV, we found the cells to be deficient in A3G messenger RNA and protein. We also noted that during DC maturation, which further reduces susceptibility to infection, A3G levels increased. These findings highlight a role for A3G/3F in explaining the resistance of most DCs to HIV-1 infection, as well as the susceptibility of a fraction of iDCs. An increase in the A3G/3F-mediated intrinsic resistance of iDCs could result in a block of HIV infection at its mucosal point of entry.

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Background-The ability to identify and ablate different arrhythmia mechanisms after the total cavopulmonary connection has not been studied in detail. Methods and Results-After obtaining Institutional Review Board approval according to institutional guidelines, consecutive patients after a total cavopulmonary connection undergoing electrophysiology study over a 6-year period were included (2006)(2007)(2008)(2009)(2010)(2011)(2012). Arrhythmia mechanism was determined, and the procedural outcome was defined as complete, partial success, or failure. A 12-point arrhythmia severity score was calculated for each patient at baseline and on follow-up. Fifty-seven procedures were performed on 52 patients (18.4±11.8 years; 53.0±27.2 kg). Access to the pulmonary venous atrium was necessary in 33 procedures, via fenestration (16) or transbaffle puncture (17), and in 2 cases, an additional retrograde approach was used. In total, 80 arrhythmias were identified in 47 cases: macroreentrant (n=25) or focal atrial tachycardia (n=8), atrioventricular nodal reentry tachycardia (n=13), reentry via an accessory pathway (n=4) or via twin atrioventricular nodes (n=4), ventricular tachycardia (n=5), and undefined atrial tachycardia (n=21). Procedural outcome in 32 patients who underwent ablation was complete success (n=25), partial success (n=3), failure (n=3), or empirical ablation (n=1). After successful ablation, there was a significant decrease in arrhythmia score over 18.2 (4-32) months follow-up, with a sustained trend even in the face of arrhythmia recurrence (50%). Conclusions-Arrhythmia mechanism post total cavopulmonary connection is highly varied, encompassing simple and more complex substrates, documentation of which facilitates a strategic approach to invasive arrhythmia management. Despite the anatomic limitations, successful and clinically meaningful ablation is possible. (Circ Arrhythm Electrophysiol. 2015;8:318-325.

The decrease of CD4+ T cells in presence of T-tropic viruses would be mainly due to a lower production of new CD4+ T cells as consequence of the inhibitory effect of these T-tropic strains on thymic function. This effect is not due either to the amount of circulating virus or to the replication kinetics of those strains, but rather depends on the ability of T-tropic viruses to infect T-cell precursors using CXCR4 receptors, which are highly expressed in immature thymocytes.

Abstract.We prove that a lower semicontinuous function defined on a reflexive Banach space is convex if and only if its Clarke subdifferential is monotone.