A Single Nucleotide in Stem Loop II of 5′-Untranslated Region Contributes to Virulence of Enterovirus 71 in Mice

BACKGROUND: Enterovirus 71 (EV71) has emerged as a neuroinvasive virus responsible for several large outbreaks in the Asia-Pacific region while virulence determinant remains unexplored. PRINCIPAL FINDINGS: In this report, we investigated increased virulence of unadapted EV71 clinical isolate 237 as compared with isolate 4643 in mice. A fragment 12 nucleotides in length in stem loop (SL) II of 237 5'-untranslated region (UTR) visibly reduced survival time and rate in mice was identified by constructing a series of infectious clones harboring chimeric 5'-UTR. In cells transfected with bicistronic plasmids, and replicon RNAs, the 12-nt fragment of isolate 237 enhanced translational activities and accelerated replication of subgenomic EV71. Finally, single nucleotide change from cytosine to uridine at base 158 in this short fragment of 5'-UTR was proven to reduce viral translation and EV71 virulence in mice. Results collectively indicated a pivotal role of novel virulence determinant C158 on virus translation in vitro and EV71 virulence in vivo. CONCLUSIONS: These results presented the first reported virulence determinant in EV71 5'-UTR and first position discovered from unadapted isolates

Recurrent infections associated with glucose-6-phosphate dehydrogenase deficiency

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Relative Osteopenia after Treatment for Acute Lymphoblastic Leukemia

Osteoporosis in adult life is associated with a significant morbidity and may be predisposed to by osteopenia and failure to reach peak bone mass in childhood. Children treated for acute lymphoblastic leukemia (ALL) may be at risk of osteopenia as a result of previous therapy or as a consequence of the disease process itself. Dual energy x-ray absorptiometry measurements of bone mineral content (BMC) for the whole body and at the lumbar spine and hip were taken in 35 (14 male) long-term survivors of ALL and compared with results in 20 (10 male) survivors of other malignancies and 31 (17 male) healthy sibling controls. The measured BMC was expressed as a percentage of a predicted value derived from the control group and based on the variables that had influence upon it. BMC (%) was reduced at the spine in the ALL group compared with controls [92.4 (8.0)% versus 100.4 (9.7)%, respectively; p < 0.005] and at the hip compared with both other malignancies and controls [89.0 (11.5)% versus 96.1 (11.7)% and 100.4 (9.2)%, respectively; p < 0.0005]. Increasing length of time off therapy was associated with a significant increase in %BMC at both the spine and the hip. For the spine, this association was significantly different between the ALL group and other malignancies, suggesting that any gain in %BMC after therapy was slower in children treated for ALL. Both exercise capacity and levels of physical activity were correlated with %BMC at the hip (r = 0.44, p < 0.001 and r = 0.29, p < 0.01, respectively). Previous exposure to methotrexate, ifosfamide, and bleomycin was associated with a reduction in %BMC at the spine. Exposure to 6-mercaptopurine and cisplatin was associated with a reduction at the hip. In conclusion, children treated for ALL are osteopenic. The mechanism is probably multifactorial but is partially related to previous chemotherapy, limited exercise capacity, and relative physical inactivity