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Fusarenon X, a member of the type B trichothecene mycotoxin group, has been frequently observed, along with deoxynivalenol (DON) and nivalenol (NIV) as a contaminant in cereals. Our previous study demonstrated that a 14-day FX exposure caused apoptosis in the lymphoid tissues of mice, especially at 0.5 mg/kg bodyweight. However, the relationship between low concentrations of FX and apoptotic molecular machinery remains unclear. In the present study, we investigated the genetic regulatory mechanisms in the thymus and Peyer's patches of mice after 14 days oral administration of FX at 0.5 mg/kg bodyweight. FX caused the up-regulation of Bax, Bid, Trp53 , and Caspase-9 mRNA but the relative expression of Fas, TNF , and Caspase-8 remained unchanged. Furthermore, we also determined the toxicity of FX in Jurkat T-cells. FX exhibited a concentration- and time-dependent inhibition of cell viability. Thus, incubation time and FX concentration influence the percentage of apoptotic cells. These data suggested that treatment with low dosage of FX can induce apoptosis in lymphocytes through an effect on Bax, Bid, Trp53, and Caspase-9 and therefore the mitochondrial apoptotic pathway. [ABSTRACT FROM AUTHOR]

Abstract: Most human enterovirus 71 (HEV71) strains infect only primates and are unable to cause clinically apparent infection in mice. Here we describe a mouse-adapted HEV71 strain that belongs to sub-genogroup B5 with increased virulence in newborn BALB/c mice. The mouse-virulent strain was initially selected by serial passage of a HEV71 clinical isolate (HEV71-B5) in Chinese hamster ovary (CHO) cells (CHO-B5), followed by serial passage in newborn mice. Virus from the fifth mouse passage was cultured twice on Vero cells and designated as MP-B5. MP-B5 induces severe disease of high mortality in newborn mice in a dose-dependent manner. Skeletal muscle is the primary site of virus replication and results in severe myositis. CHO-B5 harbours a single amino acid substitution (K149 →I) in the VP2 capsid protein. Five additional nucleotide sequence changes were identified in MP-B5, two of which are located in the 5′ UTR and the three within the open reading frame (ORF). Two of the ORF mutations resulted in deduced amino acid changes in the capsid protein VP1: S241 →L and K244 →E; the third ORF mutation was a synonymous C→T change at nucleotide position 6072 within the 3D polymerase gene. Infectious cDNA clone-derived mutant virus populations of HEV71 belonging to sub-genogroup B3 (CHO-26M) that contain the VP1 mutations identified in MP-B5 were generated in order to determine the mutation(s) responsible for mouse virulence. Only viruses expressing the VP1 (K244 →E) mutation were virulent in 5-day-old BALB/c mice, indicating that the VP1 (K244 →E) change is the critical genetic determinant of mouse adaptation and virulence in this model. [Copyright &y& Elsevier]

Abstract: Human enterovirus 71 (HEV71) has emerged as a major cause of epidemics of hand, foot and mouth disease associated with severe neurological sequelae in the Asia-Pacific region. In this study, a passive protection mouse model was used to evaluate the protective efficacy of formalin-inactivated HEV71 vaccines derived from a Chinese C4 genotype strain. Pregnant mice were immunised using a prime/boost strategy and ≥50U of vaccine protected five-day-old pups from lethal challenge with a mouse-adapted (B3 genotype) strain of HEV71. Immunised mice developed a neutralising antibody response to both the immunising C4 strain and to the mouse-adapted strain. Mice born to immunised dams showed significantly less myositis and reduced viral loads in tissues. [Copyright &y& Elsevier]