Dual-luciferase assays and inducible expression systems demonstrated that IBDV protein HIF pathway VP3 significantly inhibited IFN-beta expression stimulated by naked IBDV genomic double-stranded RNA (dsRNA). The VP3 protein competed strongly with chMDA5 to bind IBDV genomic dsRNA in vitro and in vivo, and VP3

from other birnaviruses also bound dsRNA. Site-directed mutagenesis confirmed that deletion of the VP3 dsRNA binding domain restored IFN-beta expression. Our data demonstrate that VP3 inhibits antiviral innate immunity by blocking binding of viral genomic dsRNA to MDA5. IMPORTANCE MDA5, a known pattern recognition receptor and cytoplasmic viral RNA sensor, plays a critical role in host antiviral innate immunity. Many pathogens escape or inhibit the host antiviral immune response, but the mechanisms involved are unclear for most pathogens. We report here that birnaviruses inhibit host antiviral innate immunity via the MDA5-dependent signaling pathway. The antiviral innate immune system involving MLN8237 in vivo IFN-beta did not function effectively during birnavirus infection, and the viral protein VP3 significantly inhibited IFN-beta expression stimulated by naked viral genomic dsRNA. We also show that VP3

blocks MDA5 binding to viral genomic dsRNA in vitro and in vivo. Our data reveal that birnavirus-encoded viral protein VP3 is an inhibitor of the antiviral innate immune response and inhibits the antiviral innate immune response via the MDA5-dependent signaling pathway.”
“Aim To identify the clinical features of optic nerve hypoplasia (ONH) and prevalence within a population of New Zealand children with GSK525762 severe visual impairment. Methods Retrospective review of medical records of children with severe visual impairment registered with Blind and Low Vision Educational Network New Zealand. Results Of 1500 children with severe visual impairment, 94 (6.3%) exhibited ONH, and 91 (97%) cases were bilateral. Of these 94 cases, 52 (55%) were males and ethnicities were European Caucasian (52%), Maori (40%), Pasifika (6%) and

other (2%). Most children with ONH had poor vision, with 60% having smaller than = 6/60 Snellen visual acuity equivalent. The median maternal age was 20.0 years old with 52% smaller than = 20 years. There was a statistically significant over-representation of Maori ethnicity (40%) and young maternal age with age less than 20 years old (44%) in our cohort compared to the general population (14.6% and 7.4%, respectively; p smaller than 0.0001). Half had hypopituitarism, while neuroimaging abnormalities were detected in 60% cases. Cerebral neuroradiographic abnormalities were found to be associated with higher rate of developmental delay (OR 9.764 95% CI 3.246 to 29.373). Conclusions This is the first major study of visual impairment in New Zealand children, and it demonstrates that ONH is an important cause of severe visual disability; with an over-representation of Maori children and younger maternal age.