Project description:Whole transcriptome analysis of two genetically distinctinct inbred chicken lines during NDV infection and heat stress. Background: Newcastle disease virus, in its most pathogenic form, threatens the livelihood of rural poultry farmers where there is a limited infrastructure and service for vaccinations to prevent outbreaks of the virus. Previously reported studies on the host response to Newcastle disease in chickens have not examined the disease under abiotic stressors, such as heat, which commonly experienced by chickens in regions such as Africa. The objective of this study was to elucidate the underlying biological mechanisms that contribute to disease resistance in chickens to the Newcastle disease virus while under the effects of heat stress. Results: Differential gene expression analysis identified genes differentially expressed between treated and non-treated birds across three time points (2, 6, and 10 days post-infection) in Fayoumi and Leghorn birds. Across the three time points, Fayoumi had very few genes differentially expressed between treated and non-treated groups at 2 and 6 days post-infection. However, 202 genes were differentially expressed at 10 days post-infection. Alternatively, Leghorn had very few genes differentially expressed at 2 and 10 days post-infection but had 167 differentially expressed genes at 6 days post-infection. Very few differentially expressed genes were shared between the two genetic lines, and pathway analysis found unique signaling pathways specific to each genetic line. Conclusions: The findings in this study confirmed our hypothesis that the Fayoumi line was more resistant to Newcastle disease virus infection compared to the Leghorn line. Fayoumi had significantly lower viral load, higher viral clearance, higher anti-NDV antibody levels, and fewer viral transcripts detected compared to Leghorns. Fayoumis activated immune related pathways including SAPK/JNK and p38 MAPK signaling pathways at earlier time points, while Leghorn would activate these same pathways at a later time. Further analysis revealed activation of the GP6 signaling pathway that may be responsible for the susceptible Leghorn response. Interaction analysis demonstrated substantial differences in response patterns between the two genetic lines that was not observed from the within line contrasts. This study has provided novel insights into the transcriptome response of the Harderian gland tissue during Newcastle disease virus infection while under heat stress utilizing a unique resistant and susceptible model.
Project description:We report the genetic plasticity of Newcastle disease virus. We introduced insertional mutation in the virus genome and checked fitness by comparing distribution of mutants in passage 1 and passage 2.
Project description:Lassa fever outbreaks hit West African countries every year and there is still no licensed vaccine to limit the burden of this viral hemorrhagic fever. We previously developed MeV-NP, a single-shot vaccine that induces protective immunity in cynomolgus monkeys one month or more than a year before Lassa virus infection and that is able to protect against divergent viral strains. Given the limited dissemination area of Lassa virus during outbreaks and the high risk of nosocomial transmission, a vaccine that induces rapid protection could be useful to protect exposed people during outbreaks in the absence of preventive vaccination. We tested whether the time to protection could be reduced after immunization by challenging MeV pre-immune cynomolgus monkeys 16 or 8 days after a single shot of MeV-NP. None of the immunized monkeys developed disease and they rapidly controlled viral replication. Animals immunized eight days before the challenge were the best controllers, producing a strong CD8 T-cell response against the viral glycoprotein. A group of animals was also vaccinated an hour after the challenge. These animals did not develop any protective immune responses and presented the same lethal disease as the control animals. This study demonstrates that MeV-NP can induce a rapid protective immune response against Lassa fever in presence of MeV pre-existing immunity but can likely not be used as therapeutic vaccine.
Project description:To investigate the role of gene expression during Newcastle disease virus (NDV) infection.The NDV GM strain was used to infect DEF cells with 1moi, while an uninfected group was set up as a control.
Project description:Episodic Ebola virus (EBOV) outbreaks, such as the current one in West Africa, emphasize the critical need for novel antivirals against this highly pathogenic virus. Here, we demonstrate that interferon gamma (IFNγ) prevents morbidity and mortality associated with EBOV infection when administered to mice either 24 hours prior to or 2 hours following EBOV infection. Microarray studies with IFNγ-stimulated human macrophages identified novel interferon-stimulated genes (ISGs) that inhibit EBOV infection upon ectopic expression. IFNγ treatment reduced viral RNA levels in macrophages to a similar degree as cells treated with the protein synthesis inhibitor, cycloheximide, suggesting that IFNγ treatment inhibits genome replication. As IFNγ treatment robustly protects mice against EBOV infection, we propose that this FDA-approved drug may serve as a useful prophylactic or therapeutic strategy during EBOV outbreaks, contributing to the currently limited arsenal of filovirus antivirals.
Project description:Episodic Ebola virus (EBOV) outbreaks, such as the current one in West Africa, emphasize the critical need for novel antivirals against this highly pathogenic virus. Here, we demonstrate that interferon gamma (IFNγ) prevents morbidity and mortality associated with EBOV infection when administered to mice either 24 hours prior to or 2 hours following EBOV infection. Microarray studies with IFNγ-stimulated human macrophages identified novel interferon-stimulated genes (ISGs) that inhibit EBOV infection upon ectopic expression. IFNγ treatment reduced viral RNA levels in macrophages to a similar degree as cells treated with the protein synthesis inhibitor, cycloheximide, suggesting that IFNγ treatment inhibits genome replication. As IFNγ treatment robustly protects mice against EBOV infection, we propose that this FDA-approved drug may serve as a useful prophylactic or therapeutic strategy during EBOV outbreaks, contributing to the currently limited arsenal of filovirus antivirals.