Correction: Interactions of prototype foamy virus capsids with host cell polo-like kinases are important for efficient viral DNA integration.

[This corrects the article DOI: 10.1371/journal.ppat.1005860.]

Формирование имиджа компании как работодателя: аннотация к дипломной работе / Баглай Ольга Мирославовна; Факультет философии и социальных наук; Кафедра социальной коммуникации; научный руководитель: Купчинова Татьяна Владимировна

Unlike for other retroviruses, only a few host cell factors that aid the replication of foamy viruses (FVs) via interaction with viral structural components are known. Using a yeast-two-hybrid (Y2H) screen with prototype FV (PFV) Gag protein as bait we identified human polo-like kinase 2 (hPLK2), a member of cell cycle regulatory kinases, as a new interactor of PFV capsids. Further Y2H studies confirmed interaction of PFV Gag with several PLKs of both human and rat origin. A consensus Ser-Thr/Ser-Pro (S-T/S-P) motif in Gag, which is conserved among primate FVs and phosphorylated in PFV virions, was essential for recognition by PLKs. In the case of rat PLK2, functional kinase and polo-box domains were required for interaction with PFV Gag. Fluorescently-tagged PFV Gag, through its chromatin tethering function, selectively relocalized ectopically expressed eGFP-tagged PLK proteins to mitotic chromosomes in a Gag STP motif-dependent manner, confirming a specific and dominant nature of the Gag-PLK interaction in mammalian cells. The functional relevance of the Gag-PLK interaction was examined in the context of replication-competent FVs and single-round PFV vectors. Although STP motif mutated viruses displayed wild type (wt) particle release, RNA packaging and intra-particle reverse transcription, their replication capacity was decreased 3-fold in single-cycle infections, and up to 20-fold in spreading infections over an extended time period. Strikingly similar defects were observed when cells infected with single-round wt Gag PFV vectors were treated with a pan PLK inhibitor. Analysis of entry kinetics of the mutant viruses indicated a post-fusion defect resulting in delayed and reduced integration, which was accompanied with an enhanced preference to integrate into heterochromatin. We conclude that interaction between PFV Gag and cellular PLK proteins is important for early replication steps of PFV within host cells

Azathioprine, a clastogen in human somatic cells? Analysis of chromosome damage and SCE in lymphocytes after exposure <em>in vivo </em>and <em>in vitro</em>.

Chromosomal analyses in lymphocytes of 28 patients with multiple sclerosis were carried out before, during and after Azathioprine (Aza) therapy. Only a higher incidence of gaps was found in treated patients than in a group of healthy persons but not in comparison with untreated patients. Similarly, no significant clastogenic effect was observed in vitro after short-term and long-term treatment of unstimulated and stimulated lymphocytes with concentrations of 1-100 &mu;g Aza per ml. Treatment of cultures with 0.0001-4.0 &mu;g/ml did not yield increased SCE frequencies. The absence of any significant clastogenic effect of therapeutic doses of Aza on human somatic cells is deduced from an evaluation of previously published data and from the present results

The interaction of insoluble Amyloid‐β with soluble Amyloid‐β dimers decreases Amyloid‐β plaque numbers

ObjectivesThe heterogeneity of Amyloid‐beta (Aβ) plaque load in patients with Alzheimer's disease (AD) has puzzled neuropathology. Since brain Aβ plaque load does not correlate with cognitive decline, neurotoxic soluble Aβ oligomers have been championed as disease‐causing agents in early AD. So far, investigating molecular interactions between soluble oligomeric Aβ and insoluble Aβ in vivo has been difficult because of the abundance of Aβ oligomer species and the kinetic equilibrium in which they coexist. Here, we investigated whether Aβ plaque heterogeneity relates to interactions of different Aβ conformers.Materials and MethodsWe took advantage of transgenic mice that generate exclusively Aβ dimers (tgDimer mice) but do not develop Aβ plaques or neuroinflammation during their lifetime, crossed them to the transgenic CRND8 mice that develop plaques after 90 days and measured Aβ plaque load using immunohistochemical and biochemical assays. Furthermore, we performed in vitro thioflavin T (ThT) aggregation assays titrating synthetic Aβ42‐S8C dimers into fibril‐forming synthetic Aβ42.ResultsWe observed a lower number of Aβ plaques in the brain of double transgenic mice compared to tgCRND8 mice alone while the average plaque size remained unaltered. Corroborating these in vivo findings, synthetic Aβ‐S8C dimers inhibited fibril formation of wild‐type Aβ also in vitro, seen by an increased half‐time in the ThT assay.ConclusionsOur study indicates that Aβ dimers directly interfere with Aβ fibril formation in vivo and in vitro. The variable interaction of Aβ dimers with insoluble Aβ seeds could thus contribute to the heterogeneity of Aβ plaque load in AD patients

Feedback from rhodopsin controls rhodopsin exclusion in Drosophila photoreceptors

Sensory systems with high discriminatory power use neurons that express only one of several alternative sensory receptor proteins. This exclusive receptor gene expression restricts the sensitivity spectrum of neurons and is coordinated with the choice of their synaptic targets. However, little is known about how it is maintained throughout the life of a neuron. Here we show that the green-light sensing receptor rhodopsin 6 (Rh6) acts to exclude an alternative blue-sensitive rhodopsin 5 (Rh5) from a subset of Drosophila R8 photoreceptor neurons4. Loss of Rh6 leads to a gradual expansion of Rh5 expression into all R8 photoreceptors of the ageing adult retina. The Rh6 feedback signal results in repression of the rh5 promoter and can be mimicked by other Drosophila rhodopsins; it is partly dependent on activation of rhodopsin by light, and relies on Gαq activity, but not on the subsequent steps of the phototransduction cascade. Our observations reveal a thus far unappreciated spectral plasticity of R8 photoreceptors, and identify rhodopsin feedback as an exclusion mechanism