Characterisation of a Japanese Encephalitis virus genotype 4 isolate from the 2022 Australian outbreak

npj Viruses, Journal Year: 2024, Volume and Issue: 2(1)

Published: May 10, 2024

Abstract Human infections with the Japanese encephalitis virus (JEV) are a leading cause of viral encephalitis. An unprecedented outbreak JEV genotype 4 was recently reported in Australia, an isolate (JEV NSW/22 ) obtained from stillborn piglet brain. Herein we conduct thorough characterization three different mouse strains and human cortical brain organoids (hBOs), determined ability to be neutralized by sera humans vaccinated IMOJEV. less virulent than FU (genotype 2) Nakayama 3) C57BL/6J mice interferon regulatory factor 7 deficient ( Irf7 −/− mice, infection wild-type knockout murine embryonic fibroblasts indicating is more sensitive type I responses. provide new model for , showing higher viremia levels compared allowing lethal neuroinvasive infection. All were universally Ifnar day 3, histological signs hemorrhage, but no other lesions. There indications protein detected blood vessels, not neurons. isolates showed robust cytopathic organoids, albeit lower . IMOJEV vaccination induced antibodies capable neutralizing although, all strains, cross-neutralization titers declined increasing divergence envelope amino acid sequences. Overall, our study establishes hBO models infection, possible that rarer genotypes. regimens may afford protection against this newly emerged strain, although antibody responses sub-optimal.

Language: Английский

Neurovirulence of the Australian outbreak Japanese Encephalitis virus genotype 4 is lower compared to genotypes 2 and 3 in mice and human cortical brain organoids

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: April 27, 2023

SUMMARY Background Human infections with Japanese encephalitis virus (JEV) are a leading cause of viral encephalitis. An unprecedented outbreak JEV genotype 4 was recently reported in Australia, an isolate (JEV NSW/22 ) obtained from stillborn piglet brain. Methods Herein we compared the neuropathology , FU (genotype 2) and Nakayama 3) adult C57BL/6J wild-type mice, mice deficient interferon regulatory factor 7 ( Irf7 -/- ), type I receptor Ifnar as well human cortical brain organoids (hBOs). Using serum post-Imojev vaccination, performed neutralisation assays to determine susceptibility vaccine responses. Findings In lethal outcomes, infection histopathological lesions recapitulated those seen humans primates. universally by day 3 histological signs hemorrhage, but produced no other detectable or lesions, protein detected blood vessels not neurons. We thus describe new mouse model for which had increased viremia allowing neuroinvasive one mouse. Overall, less neurovirulent than isolates more sensitive interferon. All showed robust cytopathic organoids, albeit lower . also show that Imojev vaccination induced neutralizing antibodies against level cross-neutralisation related conservation envelope amino acid sequences each isolate. Interpretation Our study establishes models infection, possible rarer genotypes. regimens may afford protection this newly emerged strain, although antibody responses sub-optimal. Funding QIMRB received generous philanthropic donation Brazil Family Foundation awarded D.J.R. support Encephalitis research at QIMRB. A.S. holds Investigator grant National Health Medical Research Council (NHMRC) Australia (APP1173880). acknowledge intramural QIMR Berghofer R.S. purchase CelVivo Clinostar incubator producing organoids. The project “Japanese via intradermal route children adults (JEVID-2): A clinical trial comparing immunogenicity safety administered subcutaneous routes” being conducted G.D., N.G., N.W. funded Sydney Children’s Hospitals Network New South Wales Health. context Evidence before historically rare causing outbreak, 44 cases fatalities. While range have been reported, none them infect efficacy current vaccines unclear. Added value establish characterised subcutaneously infected recapitulate many aspects disease including severe lesions. Prolonged significantly associated neuroinvasiveness mice. demonstrate Australian isolate, exhibited markedly diminished neuroinvasion recipients, were present, sub-optimal titers. Implications all available evidence establishment neuropenetrance after peripheral inoculation is important tool can now be deployed pre-clinical studies understand pathogenesis. suggests should developed circulating strains optimal

Language: Английский

Microplastics dysregulate innate immunity in the SARS-CoV-2 infected lung

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 21, 2023

ABSTRACT Global microplastic (MP) pollution is now well recognized, with humans and animals consuming inhaling MPs on a daily basis. Herein we described the effects of azide-free, 1 µm polystyrene MP beads co-delivered into lungs SARS-CoV-2 omicron BA.5 inoculum using mouse model mild COVID-19. Lung virus titres viral RNA levels were not significantly affected by MPs, overt clinical or histopathological changes also observed. However, RNA-Seq infected revealed that exposure suppressed innate immune responses at 2 days post infection (dpi) increased pro-inflammatory signatures 6 dpi. The cytokine profile dpi showed significant correlation ‘cytokine release syndrome’ signature seen in some severe COVID-19 patients. This study adds to growing body literature suggesting can dysregulate inflammation specific disease settings. Graphical Abstract HIGHLIGHTS A single inoculation microplastics dysregulated lung At peak decreased early Later promoted “cytokine syndrome” key mechanism may involve inhibition phagocytosis cells Azide-free used, no elevated ROS identified Postulated mechanisms whereby might decrease proinflammatory after infection, yet promote infection.

Language: Английский