We have previously demonstrated sequence discordance between proviral and plasma gag clones in ES, much of which can be attributed to selective pressure from the host (J. R. Bailey, T. M. Williams, R. F. Siliciano, and J. N. Blankson, J. Exp. Med. 203:1357-1369, 2006). However, it is not clear whether ongoing viral replication continues in ES once

the control of viremia has been established or whether selective pressure PF-4708671 ic50 impacts this evolution. The cytotoxic T-lymphocyte (CTL) response in ES often targets Gag and frequently is superior to that of HIV-1 progressors, partially due to the HLA class I alleles B*57/5801 and B*27, which are overrepresented in ES. We therefore examined longitudinal plasma and proviral gag sequences from HLA-B*57/5801 and -B*27 ES. Despite the highly conserved nature of gag, we observed clear evidence of evolution in the plasma virus, largely due to synonymous substitutions. In contrast, evolution was rare in proviral clones, suggesting that ongoing replication in find more ES does not permit the significant reseeding of the latent reservoir. Interestingly, there was little continual evolution in CTL epitopes, and we detected de novo CTL responses to autologous viral mutants. Thus, some

ES control viremia despite ongoing replication and evolution.”
“Considerable evidence indicates that native neuronal voltage-gated K+ (Kv) currents reflect the functioning of macromolecular Kv channel complexes, composed of pore-forming (alpha)-subunits, cytosolic and transmembrane accessory subunits, together with regulatory and scaffolding proteins. The individual components of these macromolecular complexes appear to influence the stability, the trafficking, GANT61 nmr the localization and/or the biophysical properties of the channels. Recent studies suggest that Kv channel accessory subunits subserve multiple roles in the generation of native neuronal Kv channels. Additional recent findings suggest that Kv channel accessory subunits can respond to changes in intracellular Ca2+ or metabolism and thereby integrate signaling pathways to regulate

Kv channel expression and properties. Although studies in heterologous cells have provided important insights into the effects of accessory subunits on Kv channel expression/properties, it has become increasingly clear that experiments in neurons are required to define the physiological roles of Kv channel accessory and associated proteins. A number of technological and experimental hurdles remain that must be overcome in the design, execution and interpretation of experiments aimed at detailing the functional roles of accessory subunits and associated proteins in the generation of native neuronal Kv channels. With the increasing association of altered Kv channel functioning with neurological disorders, the potential impact of these efforts is clear. (C) 2010 Elsevier Ireland Ltd. All rights reserved.