Ocular infection of mice with an avirulent recombinant HSV-1 expressing IL-4 and an attenuated HSV-1 strain generates virulent recombinants in vivo

PurposeTo assess the relative impact of overexpression of interleukin 2 (IL-2), interleukin 4 (IL-4), and interferon gamma (IFN-γ) expressing recombinant herpes simplex virus type 1 (HSV-1) on altering immune responses in ocularly infected mice.MethodsBALB/c mice were co-infected ocularly with avirulent HSV-1 strain KOS and avirulent recombinant HSV-1 expressing murine IL-4 (HSV-IL-4). Controls mice were co-infected with KOS + HSV-IL-2 or KOS + HSV-IFNγ. Following ocular infection, virus replication in the eye, corneal scarring (CS), and survival were determined. We also isolated recombinant viruses from eye and trigeminal ganglia of KOS + HSV-IL-4 infected mice.ResultsIn this study we found that ocular infection of BALB/c mice with a mixture of HSV-IL-4 and KOS resulted in increased death and increased eye disease. In contrast, when mice were infected in one eye with KOS and the other eye with HSV-IL-4 no death or eye disease was seen. Intraperitoneal co-infection of mice with KOS and HSV-IL-4 also did not result in HSV-1 induced death. Interestingly, ocular infection of mice with a mixture of HSV-IL-2 and KOS did not have any effect on severity of the disease in infected mice. We isolated recombinant viruses from KOS + HSV-IL-4 infected mice eye and trigeminal ganglia. Some of the isolated viruses were more neurovirulent then either parental virus. Infection of macrophages with IL-4 expressing virus down-regulated IL-12 production by macrophages.ConclusionsThese results suggest a role for IL-4 in suppression of immune response and generation of virulent viruses in vivo

A role for the JAK-STAT1 pathway in blocking replication of HSV-1 in dendritic cells and macrophages

<p>Abstract</p> <p>Background</p> <p>Macrophages and dendritic cells (DCs) play key roles in host defense against HSV-1 infection. Although macrophages and DCs can be infected by herpes simplex virus type 1 (HSV-1), both cell types are resistant to HSV-1 replication. The aim of our study was to determine factor (s) that are involved in the resistance of DCs and macrophages to productive HSV-1 infection.</p> <p>Results</p> <p>We report here that, in contrast to bone marrow-derived DCs and macrophages from wild type mice, DCs and macrophages isolated from signal transducers and activators of transcription-1 deficient (STAT1^-/-) mice were susceptible to HSV-1 replication and the production of viral mRNAs and DNA. There were differences in expression of immediate early, early, and late gene transcripts between STAT1^+/+and STAT1^-/-infected APCs.</p> <p>Conclusion</p> <p>These results suggest for the first time that the JAK-STAT1 pathway is involved in blocking replication of HSV-1 in DCs and macrophages.</p

IL-2 Suppression of IL-12p70 by a Recombinant HSV-1 Expressing IL-2 Induces T-Cell Auto-Reactivity and CNS Demyelination

To evaluate the role of cellular infiltrates in CNS demyelination in immunocompetent mice, we have used a model of multiple sclerosis (MS) in which different strains of mice are infected with a recombinant HSV-1 expressing IL-2. Histologic examination of the mice infected with HSV-IL-2 demonstrates that natural killer cells, dendritic cells, B cells, and CD25 (IL-2rα) do not play any role in the HSV-IL-2-induced demyelination. T cell depletion, T cell knockout and T cell adoptive transfer experiments suggest that both CD8+ and CD4+ T cells contribute to HSV-IL-2-induced CNS demyelination with CD8+ T cells being the primary inducers. In the adoptive transfer studies, all of the transferred T cells irrespective of their CD25 status at the time of transfer were positive for expression of FoxP3 and depletion of FoxP3 blocked CNS demyelination by HSV-IL-2. The expression levels of IL-12p35 relative to IL-12p40 differed in BM-derived macrophages infected with HSV-IL-2 from those infected with wild-type HSV-1. HSV-IL-2-induced demyelination was blocked by injecting HSV-IL-2-infected mice with IL-12p70 DNA. This study demonstrates that suppression of the IL-12p70 function of macrophages by IL-2 causes T cells to become auto-aggressive. Interruption of this immunoregulatory axis results in demyelination of the optic nerve, the spinal cord and the brain by autoreactive T cells in the HSV-IL-2 mouse model of MS

Functional mapping of quantitative trait loci (QTLs) associated with plant performance in a wheat MAGIC mapping population

In crop genetic studies, the mapping of longitudinal data describing the spatio-temporal nature of agronomic traits can elucidate the factors influencing their formation and development. Here, we combine the mapping power and precision of a MAGIC wheat population with robust computational methods to track the spatio- temporal dynamics of traits associated with wheat performance. NIAB MAGIC lines were phenotyped throughout their lifecycle under smart house conditions. Growth models were fitted to the data describing growth trajectories of plant area, height, water use and senescence and fitted parameters were mapped as quantitative traits. Trait data from single time points were also mapped to determine when and how markers became and ceased to be significant. Assessment of temporal dynamics allowed the identification of marker-trait associations and tracking of trait development against the genetic contribution of key markers. We establish a data-driven approach for understanding complex agronomic traits and accelerate research in plant breeding

Homeowner's Guide to Pests of Peaches, Plums and Pecans

9 pp., 6 tablesTo deal with insect and disease problems on peaches, plums and pecans, it is necessary to understand the life cycles of pests and diseases. Pesticide safety instructions and spray equipment also are discussed, and spray schedules are provided

Development and Testing of Cool-Season Grass Species, Varieties and Hybrids for Biomass Feedstock Production in Western North America

Breeding of native cool-season grasses has the potential to improve forage production and expand the range of bioenergy feedstocks throughout western North America. Basin wildrye (Leymus cinereus) and creeping wildrye (Leymus triticoides) rank among the tallest and most rhizomatous grasses of this region, respectively. The objectives of this study were to develop interspecific creeping wildrye (CWR) × basin wildrye (BWR) hybrids and evaluate their biomass yield relative to tetraploid ‘Trailhead’, octoploid ‘Magnar’ and interploidy-hybrid ‘Continental’ BWR cultivars in comparison with other perennial grasses across diverse single-harvest dryland range sites and a two-harvest irrigated production system. Two half-sib hybrid populations were produced by harvesting seed from the tetraploid self-incompatible Acc:641.T CWR genet, which was clonally propagated by rhizomes into isolated hybridization blocks with two tetraploid BWR pollen parents: Acc:636 and ‘Trailhead’. Full-sib hybrid seed was also produced from a controlled cross of tetraploid ‘Rio’ CWR and ‘Trailhead’ BWR plants. In space-planted range plots, the ‘Rio’ CWR × ‘Trailhead’ BWR and Acc:641.T CWR × Acc:636 BWR hybrids displayed high-parent heterosis with 75% and 36% yield advantages, respectively, but the Acc:641.T CWR × ‘Trailhead’ BWR hybrid yielded significantly less than its BWR high-parent in this evaluation. Half-sib CWR × BWR hybrids of Acc:636 and ‘Trailhead’ both yielded as good as or better than available BWR cultivars, with yields similar to switchgrass (Panicum virgatum), in the irrigated sward plots. These results elucidate opportunity to harness genetic variation among native grass species for the development of forage and bioenergy feedstocks in western North America

An alternative strategy for trypanosome survival in the mammalian bloodstream revealed through genome and transcriptome analysis of the ubiquitous bovine parasite Trypanosoma (Megatrypanum) theileri

There are hundreds of Trypanosoma species that live in the blood and tissue spaces of their vertebrate hosts. The vast majority of these do not have the ornate system of antigenic variation that has evolved in the small number of African trypanosome species, but can still maintain long term infections in the face of the vertebrate adaptive immune system. Trypanosoma theileri is a typical example, it has a restricted host range of cattle and other Bovinae and is only occasionally reported to cause patent disease although no systematic survey of the effect of infection on agricultural productivity has been performed. Here, a detailed genome sequence and a transcriptome analysis of gene expression in bloodstream form T. theileri have been performed. Analysis of the genome sequence and expression showed that T. theileri has a typical kinetoplastid genome structure and allowed a prediction that it is capable of meiotic exchange, gene silencing via RNA interference and, potentially, density-dependent growth control. In particular, the transcriptome analysis has allowed a comparison of two distinct trypanosome cell surfaces, T. brucei and T. theileri, that have each evolved to enable the maintenance of a long-term extracellular infection in cattle. The T. theileri cell surface can be modelled to contain a mixture of proteins encoded by four novel large and divergent gene families and by members of a major surface protease gene family. This surface composition is distinct from the uniform variant surface glycoprotein coat on African trypanosomes providing an insight into a second mechanism used by trypanosome species that proliferate in an extracellular milieu in vertebrate hosts to avoid the adaptive immune response

Inclusion of CD80 in HSV Targets the Recombinant Virus to PD-L1 on DCs and Allows Productive Infection and Robust Immune Responses

CD80 plays a critical role in stimulation of T cells and subsequent control of infection. To investigate the effect of CD80 on HSV-1 infection, we constructed a recombinant HSV-1 virus that expresses two copies of the CD80 gene in place of the latency associated transcript (LAT). This mutant virus (HSV-CD80) expressed high levels of CD80 and had similar virus replication kinetics as control viruses in rabbit skin cells. In contrast to parental virus, this CD80 expressing recombinant virus replicated efficiently in immature dendritic cells (DCs). Additionally, the susceptibility of immature DCs to HSV-CD80 infection was mediated by CD80 binding to PD-L1 on DCs. This interaction also contributed to a significant increase in T cell activation. Taken together, these results suggest that inclusion of CD80 as a vaccine adjuvant may promote increased vaccine efficacy by enhancing the immune response directly and also indirectly by targeting to DC

Thermoelectric model to characterize carrier transport in organic semiconductors

A model for the Seebeck coefficient in the regime of hopping transport that includes the effects of Gaussian carrier density of states width and carrier localization allows these parameters to be derived independently of the attempt-to-jump rate, which can subsequently be derived from measured electrical conductivity. This model is applied to prototypical small molecular and polymer organic semiconductors to characterize carrier localization, quantify the role of dopants on the hopping transport parameters, and derive the effective dopant ionization fraction and activation energy.clos