Expected and Unexpected Features of the Newly Discovered Bat Influenza A-like Viruses

Citation: Ma, W. J., Garcia-Sastre, A., & Schwemmle, M. (2015). Expected and Unexpected Features of the Newly Discovered Bat Influenza A-like Viruses. Plos Pathogens, 11(6), 6. doi:10.1371/journal.ppat.1004819Influenza A viruses (IAVs) are important zoonotic pathogens that cause epidemic outbreaks in poultry, wild birds, swine, and other mammals. In humans, IAVs cause severe respiratory illness, and zoonotic transmission of IAVs from avian reservoirs poses a constant threat to the public health, as exemplified by the recent outbreak of an avian IAV of the H7N9 subtype [1]. Aquatic birds are considered to be the major reservoir of IAVs, and 16 hemagglutinin (HA) and nine neuraminidase (NA) viral subtypes have been isolated from avian species to date. It is now well documented that from time to time IAVs overcome the species barrier and establish new lineages in other animals, including domestic animals, sea mammals, and humans (Fig 1). Our understanding of IAVs was recently challenged by the identification of two novel genome sequences of influenza A-like viruses from bat specimens by next-generation sequencing. These viruses were provisionally designated "H17N10" (from yellow-shouldered fruit bats [Sturnira lilium] in Guatemala) and "H18N11" (from flat-faced fruit bats [Artibeus planirostris] in Peru) [2,3], which might signal an expansion of IAV host range (Fig 1)

Laser performance of Coumarin 540A dye molecules in polymeric host media with different viscosities: From liquid solution to solid polymer matrix

11 pages, 12 figures, 3 tables.-- PACS: 42.70.Hj; 42.55.Rz; 42.55.Mv; 66.20.+d; 78.55.Bq; 78.55.KzPhotophysical parameters and lasing properties of Coumarin 540A dye molecules are studied in solutions of increasing viscosity, from liquid solutions in 1,4-dioxane to solid solutions in poly(methyl methacrylate). The fluorescence quantum yield and lasing efficiencies decrease as the viscosity of the solution increases, reflecting the strong influence of the rigidity of the medium on the radiative processes. The photodegradation mechanisms acting on the fluorophores are analyzed by following the dependence of laser induced fluorescence and laser output on the number of pump laser pulses. The fluorescence redistribution after pattern photobleaching technique is used, and Fick's second law is applied to study the diffusion of dye molecules in the highly viscous polymer solutions. The diffusion coefficients of the dye molecules as a function of the increased viscosity of the medium are determined.This work was supported by the Spanish CICYT Project MAT94-0757.Peer reviewe

Highly photostable solid-state dye lasers based on silicon-modified organic matrices

11 pages, 13 figures, 4 tables.-- PACS: 42.55.Rz; 42.60.FcWe report on the synthesis, characterization, and physical properties of modified polymeric matrices incorporating silicon atoms in their structure and doped with laser dyes. When the silicon-modified organic matrices incorporated pyrromethene 567 (PM567) and pyrromethene 597 (PM597) dyes as actual solid solutions, highly photostable laser operation with reasonable, nonoptimized efficiencies was obtained under transversal pumping at 532 nm. At a pump repetition rate of 10 Hz, the intensity of the laser emission remained at the level or above the initial lasing intensity after 100 000 pump pulses in the same position of the sample, corresponding to an estimated accumulated pump energy absorbed by the system of 518 and 1295 GJ/mol for PM567 and PM597, respectively. When the pump repetition rate was increased to 30 Hz, the laser emission of dye PM567 decreased steadily and the output energy fell to one-half its initial value after an accumulated pump energy of 989 GJ/mol. Dye PM597 demonstrated a remarkable photostability, and under 30 Hz pumping the laser emission from some samples remained stable after 700 000 pump pulses in the same position of the sample, corresponding to an accumulated pump energy of 17 300 GJ/mol. Narrow linewidth operation with tuning ranges of up to 31 nm was obtained with both pyrromethene dyes when some of the samples were incorporated into a grazing-incidence grating oscillator.This work was supported by Project Nos. 7N/0100/02 of the Comunidad Autónoma de Madrid ( CAM) and MAT2004- 04643-C03-01 of the Spanish CICYT. One of the authors (O.G.) thanks the MEC for awarding her a Ramón y Cajal scientific contract. Another author (D.A.) thanks CAM for a predoctoral scholarship.Peer reviewe

Confirmation of involvement of new variants at CDKN2A/B in pediatric acute lymphoblastic leukemia susceptibility in the Spanish population

The locus CDKN2A/B (9p21.3), which comprises the tumor suppressors genes CDKN2A and CDKN2B and the long noncoding RNA (lncRNA) known as ANRIL (or CDKN2B-AS), was associated with childhood acute lymphoblastic leukemia (ALL) susceptibility in several genome wide association studies (GWAS). However, the variants associated in the diverse studies were different. Recently, new and independent SNPs deregulating the locus function were also identified in association with ALL risk. This diversity in the results may be explained because different variants in each population could alter CDKN2A/B locus function through diverse mechanisms. Therefore, the aim of this study was to determine whether the annotated risk variants in the CDKN2A/B locus affect the susceptibility of B cell precursor ALL (B-ALL) in our Spanish population and explore if other SNPs altering additional regulatory mechanisms could be also involved. We analyzed the four SNPs proposed by GWAs and two additional SNPs in miRNA binding sites in 217 pediatric patients with B-ALL and 330 healthy controls. The SNPs rs2811712, rs3731249, rs3217992 and rs2811709 were associated with B-ALL susceptibility in our Spanish population. ALL subtypes analyses showed that rs2811712 was associated with B-hyperdiploid ALL. These results provide evidence for the influence of genetic variants at CDKN2A/B locus with the risk of developing B-ALL

Influenza virus differentially activates mTORC1 and mTORC2 signaling to maximize late stage replication

<div><p>Influenza A virus usurps host signaling factors to regulate its replication. One example is mTOR, a cellular regulator of protein synthesis, growth and motility. While the role of mTORC1 in viral infection has been studied, the mechanisms that induce mTORC1 activation and the substrates regulated by mTORC1 during influenza virus infection have not been established. In addition, the role of mTORC2 during influenza virus infection remains unknown. Here we show that mTORC2 and PDPK1 differentially phosphorylate AKT upon influenza virus infection. PDPK1-mediated phoshorylation of AKT at a distinct site is required for mTORC1 activation by influenza virus. On the other hand, the viral NS1 protein promotes phosphorylation of AKT at a different site via mTORC2, which is an activity dispensable for mTORC1 stimulation but known to regulate apoptosis. Influenza virus HA protein and down-regulation of the mTORC1 inhibitor REDD1 by the virus M2 protein promote mTORC1 activity. Systematic phosphoproteomics analysis performed in cells lacking the mTORC2 component Rictor in the absence or presence of Torin, an inhibitor of both mTORC1 and mTORC2, revealed mTORC1-dependent substrates regulated during infection. Members of pathways that regulate mTORC1 or are regulated by mTORC1 were identified, including constituents of the translation machinery that once activated can promote translation. mTORC1 activation supports viral protein expression and replication. As mTORC1 activation is optimal midway through the virus life cycle, the observed effects on viral protein expression likely support the late stages of influenza virus replication when infected cells undergo significant stress.</p></div

Tonsilar NK Cells Restrict B Cell Transformation by the Epstein-Barr Virus via IFN-γ

Cells of the innate immune system act in synergy to provide a first line of defense against pathogens. Here we describe that dendritic cells (DCs), matured with viral products or mimics thereof, including Epstein-Barr virus (EBV), activated natural killer (NK) cells more efficiently than other mature DC preparations. CD56brightCD16− NK cells, which are enriched in human secondary lymphoid tissues, responded primarily to this DC activation. DCs elicited 50-fold stronger interferon-γ (IFN-γ) secretion from tonsilar NK cells than from peripheral blood NK cells, reaching levels that inhibited B cell transformation by EBV. In fact, 100- to 1,000-fold less tonsilar than peripheral blood NK cells were required to achieve the same protection in vitro, indicating that innate immune control of EBV by NK cells is most efficient at this primary site of EBV infection. The high IFN-γ concentrations, produced by tonsilar NK cells, delayed latent EBV antigen expression, resulting in decreased B cell proliferation during the first week after EBV infection in vitro. These results suggest that NK cell activation by DCs can limit primary EBV infection in tonsils until adaptive immunity establishes immune control of this persistent and oncogenic human pathogen

Involvement of SNPs in miR-3117 and miR-3689d2 in childhood acute lymphoblastic leukemia risk

Acute lymphoblastic leukemia (ALL) is the most common cancer in children. Numerous studies have shown that microRNAs (miRNAs) could play a role in this disease. Nowadays, more than 2500 miRNAs have been described, that regulate more than 50% of genes, including those involved in B-cell maturation, differentiation and proliferation. Genetic variants in miRNAs can alter their own levels or function, affecting their target gene expression, and then, may affect ALL risk. Therefore, the aim of this study was to determine the role of miRNA genetic variants in B-ALL susceptibility. We analyzed all variants in pre-miRNAs (MAF > 1%) in two independent cohorts from Spain and Slovenia and inferred their functional effect by in silico analysis. SNPs rs12402181 in miR-3117 and rs62571442 in miR-3689d2 were associated with ALL risk in both cohorts, possibly through their effect on MAPK signalling pathway. These SNPs could be novel markers for ALL susceptibility

Laser performance of pyrromethene 567 dye in solid polymeric matrices with different cross-linking degrees

We report on the laser action of pyrromethene 567 ͑PM567͒ incorporated into copolymers of methyl methacrylate ͑MMA͒ with different methacrylic and acrylic cross-linking monomers: ethyleneglycol dimethacrylate, trimethylolpropane trimethacrylate, tetraethyleneglycol diacrylate, pentaerythritol triacrylate, and pentaerythritol tetraacrylate ͑PETRA͒. The vol/vol proportion of the different co-monomers in each copolymer formulation was systematically varied, and the effect of each composition on the lasing properties of PM567 was evaluated. The laser samples were transversely pumped at 534 nm with 5.5 mJ/pulse from a frequency doubled Q-switched Nd:KGW laser. Lasing efficiencies of up 26% and good stability with a drop of the initial laser output of 30% after 100 000 pump pulses at 5 Hz in P͑MMA:PETRA 95:5͒ were demonstrated

8-PropargylaminoBODIPY: unprecedented blue-emitting pyrromethene dye. Synthesis, photophysics and laser properties

Highly emitting 8-propargylaminoBODIPY (8-PAB) 2 was prepared in 94% yield. Unlike any other BODIPY structure hitherto described in the literature, 2 displays efficient emission in the blue region of the visible spectrum with a fluorescence quantum yield up to 0.94 and high laser efficiency (35%) at 483 nm.Grants GTO-2007-C02-69094 (CONCyTEG) (Mexico), MAT2007-65778-C02-01 and -02 of the Spanish MICINN are gratefully acknowledged. V. Martin thanks CSIC for her JAE-postdoctoral contract.Peer reviewe

Bichromatic laser emission from dipyrromethene dyes incorporated into solid polymeric media

9 pages, 9 figures.Bichromatic laser emission from dipyrromethene-based solid-state dye lasers is reported. The dependence of this dual emission on different factors and its origin and causes are discussed in the light of different models proposed in the literature. Our experimental results indicate that the long-wavelength emission can be explained in terms of reabsorption/reemission effects and inhomogeneous broadening of the S0-S1 transition. The short-wavelength emission corresponds to the usual S0-S1 transition and dominates at low dye concentration.This work was supported by Project Nos. MAT2004-04643-C03-01 and MAT2004-04643-C03-02 of the Spanish CICYT. One of the authors (M.Á.) thanks Ministerio de Ciencia y Tecnología (MCT) for a predoctoral grant. Another author (M.L.) thanks Comunidad Autónoma de Madrid for a postdoctoral grant and MCT for a Juan de la Cierva contract.Peer reviewe