The interferon (IFN) system is integral to the host response against viruses, and many viruses have developed strategies to overcome its antiviral effects. The effects of hepatitis E virus (HEV), the causative agent of hepatitis E, on IFN signaling have not been investigated primarily because of the nonavailability of an efficient in vitro culture system or small animal models of infection. We report here the generation of A549 cell lines persistently infected with genotype 3 HEV, designated as HEV-A549 cells and the effects HEV has on IFN-a-mediated Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling. Treatment of HEV-A549 cells with 250, 500, and 1000 U/mL of IFN-a for 72 hours showed a dose-dependent reduction in HEV RNA levels by 10%, 20%, and 50%, respectively. IFN-a-stimulated genes coding for the antiviral proteins dsRNA-activated protein kinase (PKR) and 2 0 ,5 0 -oligoadenylate synthetase (2 0 ,5 0 -OAS) were downregulated in IFN-a-treated HEV-A549 cells. HEV infection also prevented IFN-a-induced phosphorylation of STAT1. Regulation of STAT1 by HEV was specific, as phosphorylation of STAT2, tyrosine kinase (Tyk) 2, and Jak1 by IFN-a was unaltered. Additionally, STAT1 levels were markedly increased in HEV-A549 cells compared with naive A549 cells. Acute viral infection of susceptible host cells initiates a type I interferon (IFN) response that is composed predominantly of interferon-a and -b (IFNa/b) signaling through the IFN-a receptor. IFN-a/b receptor binding results in receptor subunit dimerization and activation through tyrosine phosphorylation of two tyrosine kinases of the Janus family, Janus kinase 1(Jak1) and tyrosine kinase 2 (Tyk2), which then phosphorylate signal transducer and activator of transcription (STAT) 1 and STAT2 on a single tyrosine residue, leading to STAT1-STAT2 heterotrimerization with interferon regulatory factor (IRF) 9 followed by nuclear localization.
To conduct crewed simulation experiments of bioregenerative life support systems on the ground is a critical step for human life support in deep-space exploration. An artificial closed ecosystem named Lunar Palace 1 was built through integrating efficient higher plant cultivation, animal protein production, urine nitrogen recycling, and bioconversion of solid waste. Subsequently, a 105-day, multicrew, closed integrative bioregenerative life support systems experiment in Lunar Palace 1 was carried out from February through May 2014. The results show that environmental conditions as well as the gas balance between O and CO in the system were well maintained during the 105-day experiment. A total of 21 plant species in this system kept a harmonious coexistent relationship, and 20.5% nitrogen recovery from urine, 41% solid waste degradation, and a small amount of insect in situ production were achieved. During the 105-day experiment, oxygen and water were recycled, and 55% of the food was regenerated. Key Words: Bioregenerative life support systems (BLSS)-Space agriculture-Space life support-Waste recycle-Water recycle. Astrobiology 16, 925-936.
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