20 research outputs found

    Constitutive expression and distinct properties of IFN-epsilon protect the female reproductive tract from Zika virus infection

    Get PDF
    The immunological surveillance factors controlling vulnerability of the female reproductive tract (FRT) to sexually transmitted viral infections are not well understood. Interferon-epsilon (IFNε) is a distinct, immunoregulatory type-I IFN that is constitutively expressed by FRT epithelium and is not induced by pathogens like other antiviral IFNs α, β and λ. We show the necessity of IFNε for Zika Virus (ZIKV) protection by: increased susceptibility of IFNε -/- mice; their “rescue” by intravaginal recombinant IFNε treatment and blockade of protective endogenous IFNε by neutralising antibody. Complementary studies in human FRT cell lines showed IFNε had potent anti-ZIKV activity, associated with transcriptome responses similar to IFNλ but lacking the proinflammatory gene signature of IFNα. IFNε activated STAT1/2 pathways similar to IFNα and λ that were inhibited by ZIKV-encoded non-structural (NS) proteins, but not if IFNε exposure preceded infection. This scenario is provided by the constitutive expression of endogenous IFNε. However, the IFNε expression was not inhibited by ZIKV NS proteins despite their ability to antagonise the expression of IFNβ or λ. Thus, the constitutive expression of IFNε provides cellular resistance to viral strategies of antagonism and maximises the antiviral activity of the FRT. These results show that the unique spatiotemporal properties of IFNε provides an innate immune surveillance network in the FRT that is a significant barrier to viral infection with important implications for prevention and therapy.Rosa C. Coldbeck-Shackley, Ornella Romeo, Sarah Rosli, Linden J. Gearing, Jodee A. Gould, San S. Lim, Kylie H. Van der Hoek, Nicholas S. Eyre, Byron Shue, Sarah A. Robertson, Sonja M. Best, Michelle D. Tate, Paul J. Hertzog, Michael R. Bear

    A petrographic study of lunar meteorite Northeast Africa

    No full text
    We present a petrographic study of the lunar meteorite NEA 001 — a feldspathic regolith breccia with a VLT mare basalt component

    Viperin binds STING and enhances the type-I interferon response following dsDNA detection

    No full text
    First published: 01 November 2020Viperin is an interferon-inducible protein that is pivotal for eliciting an effective immune response against an array of diverse viral pathogens. Here we describe a mechanism of viperin's broad antiviral activity by demonstrating the protein's ability to synergistically enhance the innate immune dsDNA signalling pathway to limit viral infection. Viperin co-localised with the key signalling molecules of the innate immune dsDNA sensing pathway, STING and TBK1; binding directly to STING and inducing enhanced K63-linked polyubiquitination of TBK1. Subsequent analysis identified viperin's necessity to bind the cytosolic iron-sulphur assembly component 2A, to prolong its enhancement of the type-I interferon response to aberrant dsDNA. Here we show that viperin facilitates the formation of a signalling enhanceosome, to coordinate efficient signal transduction following activation of the dsDNA signalling pathway; which results in an enhanced antiviral state. We also provide evidence for viperin's radical SAM enzymatic activity to self-limit its immunomodulatory functions. These data further define viperin's role as a positive regulator of innate immune signalling, offering a mechanism of viperin's broad antiviral capacity.Keaton M Crosse, Ebony A Monson, Arti B Dumbrepatil, Monique Smith, Yeu-Yang Tseng, Kylie H Van der Hoe

    Níveis séricos de hemoglobina em adolescentes segundo estágio de maturação sexual Hemoglobin serum levels in adolescents according to sexual maturation stage

    No full text
    A adolescência constitui etapa de risco para o desenvolvimento da anemia ferropriva, uma vez que ocorre aumento da necessidade de ferro decorrente do crescimento estatural e da maturação biológica. Estudaram-se 130 adolescentes, de ambos os sexos, para verificar os valores de hemoglobina sérica em diferentes fases de maturação sexual. Utilizou-se o método de fotometria para dosar a hemoglobina sérica e realizou-se auto-avaliação do estágio de maturação sexual com base nos critérios de Tanner. Os níveis médios de hemoglobina foram semelhantes entre sexos, bem como entre meninas que menstruavam ou não. O nível médio de hemoglobina foi de 13,3g/dL tanto para os meninos como para as meninas (p=0,64), com desvios-padrão de 1,12 e de 0,83, respectivamente. Entre os adolescentes estudados, 7,7% tinham anemia ferropriva. Recomenda-se atenção ao grupo de adolescentes, devido ao aumento da necessidade de ferro durante o estirão de crescimento, principalmente entre as meninas, aumentando a suscetibilidade à anemia.<br>During adolescence, the risk of development of iron-deficiency anemia is higher because of the growth spurt and the sexual maturation which increase the iron requirement. One hundred and thirty adolescents (males and females) were studied, in order to assess the serum hemoglobin values in different sexual maturation stages. The photometric method was used and a self-evaluation of the sexual maturation stage based on Tanner's criteria was applied. The average hemoglobin values were similar for both sexes, as well for girls who had menstruated or not. The average hemoglobin values were 13.3 (s.d. 1.12)g/dL for males and 13.3 (s.d. 0.83)g/dL for females (p=0.64). Among the studied adolescents, 7.7% had iron-deficiency anemia. Due to the iron requirement increase during the growth spurt, mainly in females, and the higher susceptibility to iron deficiency anemia, special attention to the adolescents is recommended

    Eroding abodes and vanished bridges: historical biogeography of the substrate specialist pebble-mound mice (Pseudomys).

    No full text
    Aim: To determine whether the pronounced ecological importance of pebble mounds to pebble-mound mice (Pseudomys) is manifest in their continental biogeography.\ud \ud Location: Northern Australia.\ud \ud Methods: A GIS-based comparison was made between the habitats contained within the potential climatic distributions of mice, representing a null hypothesis of no habitat selection, and their actual distributions based on all known location records.\ud \ud Results: All species had a clear preference for hilly, rocky landscapes with a surficial cover dominated by bedrock. Simple vegetation communities with relatively open eucalypt overstorey and grassy understorey were preferred. Highly degraded rocks and aggradational surfaces and plains were avoided. The extent of the summer monsoon may be important in determining the southern limits of the group's distribution. Major disjunctions between species were attributable to the presence of clay plains and sand sheets.\ud The behavioural requirement of pebble-mound mice for mounds determines their population distribution pattern and the distribution of the different species within the genus.\ud \ud Main conclusions: The behavioural need for pebble mounds drives the distributional pattern of populations and species of pebble-mound mice. The initial spread of pebble-mound mice probably occurred during the late Pliocene or earliest Pleistocene. There has predominantly been degradation of the potential distribution of the group since that time due to the stability of Australian landscapes and Pleistocene planation and sand sheet development over large areas of northern Australia. This process is ongoing, and past regions of rocky contact between current distributions have disappeared, while the distributional limits of several species are steadily being reduced by erosion of hills and the spread of dune fields
    corecore