Factors responsible for pathogenicity in chickens of a low-pathogenic H7N7 avian influenza virus isolated from a feral duck

Highly pathogenic avian influenza viruses have poly-basic amino acid sequences at the cleavage site in their hemagglutinin (HA). Although this poly-basic region is a prerequisite factor for pathogenicity in chickens, not much is known about additional factors responsible for the acquisition of pathogenicity of the duck influenza virus in chickens. Here, we introduced multiple basic amino acid residues into the HA cleavage site of the A/duck/Hokkaido/Vac-2/2004 (H7N7) strain of avian influenza virus, which has low pathogenicity in chickens; the resultant Vac2sub-P0 strain was not intravenously pathogenic in chickens. In contrast, the Vac2sub-P3 strain, which was recovered from three consecutive passages of Vac2sub-P0 in chicks, was intravenously pathogenic in chickens. Six amino acid substitutions were identified by comparison of the Vac2sub-P3 and Vac2sub-P0 genomic sequences: Lys123Glu in PB2, Asn16Asp in PB1, Glu227Gly and Ile388Thr in HA, Gly228Arg in M1, and Leu46Pro in M2. The results of intravenous inoculations of chickens with recombinant virus indicated that all six amino acid substitutions were required to varying degrees for Vac2sub-P3 pathogenicity, with Glu227Gly and Ile388Thr in HA being particularly essential. These results reveal the roles of additional viral factors in the acquisition of pathogenicity in addition to the previously characterized role of the poly-basic amino acid sequences at the HA cleavage site.     

Renal replacement therapy with a cytokine‐adsorbing hemofilter after neonatal open-heart surgery

Journal of Artificial Organs - Two neonates with right atrial isomerism, single right ventricle, common atrioventricular valve regurgitation, and obstructive extra-cardiac total anomalous pulmonary...     

Parp‐1 deficiency in ES cells promotes invasive and metastatic lesions accompanying induction of trophoblast giant cells during tumorigenesis in uterine environment

Embryonic stem (ES) cells deficient in poly(ADP‐ribose) polymerase‐1 (Parp‐1) develop into teratocarcinomas with the appearance of trophoblast giant cells (TGCs) when injected subcutaneously into nude mice. Because the uterus is one of the original organs in which germ cell tumors develop with induction of trophoblast lineage, here we investigated whether Parp‐1 deficiency in ES cells affects teratocarcinoma formation processes by grafting ES cells into the horns of uteri. Teratocarcinomas developed from both wild‐type (Parp‐1^+/+) and Parp‐1^?/? ES cells. The weights of the tumors derived from Parp‐1^?/? ES cells were lower than those of the tumors derived from Parp‐1^+/+ ES cells (P < 0.05). The Parp‐1^?/? tumors showed the appearance of TGCs. Notably, organ metastasis to the lung and liver was observed for the Parp‐1^?/? tumors, but not for the Parp‐1^+/+ tumors (P < 0.05). Invasions were more frequently observed with the Parp‐1^?/? tumors compared with the Parp‐1^+/+ tumors (P < 0.05). Since TGCs are known to have invasive properties, the appearance of TGCs may have supported the metastatic process. The present findings suggest that loss of Parp‐1 during teratocarcinoma formation might augment invasive and metastatic properties of the tumors in the uterine environment.