Innate Immunity to Adenovirus

Human adenoviruses are the most widely used vectors in gene medicine, with applications ranging from oncolytic therapies to vaccinations, but adenovirus vectors are not without side effects. In addition, natural adenoviruses pose severe risks for immuno-compromised people, yet, infections are usually mild and self-limiting in immuno-competent individuals. Here we describe how adenoviruses are recognized by the host innate defense system during entry and replication in immune and non-immune cells. Innate defense protects the host, and at the same time, represents a major barrier to using adenoviruses as therapeutic interventions in humans. Innate response against adenoviruses involves intrinsic factors present at constant levels, and innate factors induced by the host cell upon viral challenge. These factors exert anti-viral effects by directly binding to viruses or viral components, or shield the virus, for example soluble factors, such as blood clotting components, the complement system, preexisting immunoglobulins or defensins. In addition, toll-like receptors and lectins in the plasma membrane and endosomes are intrinsic factors against adenoviruses. Important innate factors restricting adenovirus in the cytosol are tripartite motif-containing proteins (TRIM), nucleotide-binding oligomerization domain (NOD)-like inflammatory receptors and DNA sensors triggering interferon, such as DEAD (Asp-Glu-Ala-Asp) box polypeptide 41 (DDX41) and cyclic guanosine monophosphate-adenosine monophosphate synthase (cGMP-AMP synthase, short cGAS). Adenovirus tunes the function of anti-viral autophagy, and counters innate defense by virtue of its early proteins E1A, E1B, E3 and E4 and two virus-associated noncoding RNAs VA-I and VA-II. We conclude by discussing strategies to engineer adenovirus vectors with attenuated innate responses and enhanced delivery features

Sex pheromones of rice moth,Corcyra cephalonica Stainton

International audienceBehavioral observations of the rice moth (Corcyra cephalonica, Pyralidae, Galleriinae) in the laboratory have shown that a male wing-gland pheromone induces attraction of female moths. This pheromone was identified as a blend of (E,E) and (Z,E)-farnesal. Wing-gland extracts or synthetic compounds were shown to be attractive to females by inducing walking

Mad2 Is a Critical Mediator of the Chromosome Instability Observed upon Rb and p53 Pathway Inhibition

Multiple mechanisms have been proposed to explain how Rb and p53 tumor suppressor loss lead to chromosome instability (CIN). It was recently shown that Rb pathway inhibition causes overexpression of the mitotic checkpoint gene Mad2, but whether Mad2 overexpression is required to generate CIN in this context is unknown. Here, we show that CIN in cultured cells lacking Rb family proteins requires Mad2 upregulation and that this upregulation is also necessary for CIN and tumor progression in vivo. Mad2 is also repressed by p53 and its upregulation is required for CIN in a p53 mutant tumor model. These results demonstrate that Mad2 overexpression is a critical mediator of the CIN observed upon inactivation of two major tumor suppressor pathways

Behavioral observations and measurements of aerial pheromone in a mating disruption trial against pea moth Cydia nigricana F (Lepidoptera, Tortricidae)

Synthetic sex pheromone of the pea moth Cydia nigricana, (E,E)-8,10-dodecadien-1-yl acetate (E8,E10-12:Ac), was applied in a 3-ha pea field at a rate of 17 g/ha, in two different dispenser formulations. Aerial concentrations within pea canopy, as determined by a field electroantennogram (EAG) apparatus, were 2 and 3 ng/m(3) in the two dispenser treatments. The validity of the EAG measurements was corroborated by sampling of field air, followed by gas chromatographic quantification of E8,E10-12:Ac. Males were attracted to fresh dispensers releasing E8,E10-12:Ac plus less than 2% of the antagonistic E, Z; Z, E; and Z, Z isomers. Two days after placement, the proportion of these isomers had increased to 6%. Males were then no longer attracted to the dispensers, but were observed to fly out of the treated field. Male attraction to calling females was almost entirely suppressed, and attraction to traps baited with synthetic pheromone was significantly reduced. Larval infestation in the pheromone-treated field was 2%, compared to 36% in a control field