The mechanism of liver injury by hepatitis B virus, using a novel adenovirus expressing HBV

静脉注射表达HBV的腺病毒（adeno-HBV）至BALB/c小鼠后5天，血清HBsAg显示峰值，而在随访期间，adeno-GFP（对照病毒）注射小鼠中没有升高。在注射腺病毒HBV或腺病毒GFP的小鼠中，注射后1天肝内淋巴细胞的数量增加，表明这种效应是由于腺病毒本身。然而，在注射后5天，NK细胞的数量再次增加，而在adeno-GFP注射的小鼠中没有增加。两种腺病毒注射后第1天，CD 1d四聚体阳性细胞数均减少。在腺-GFP注射的小鼠中，CD 1d四聚体阳性细胞的数量在几天内恢复。相反，直到注射腺病毒后10天才恢复。使用Yac-1细胞的NK细胞毒性在注射两种病毒后1天上调。然后，在腺病毒-GFP注射的小鼠中逐渐恢复正常，而iNK细胞毒性在腺病毒-HBV注射的小鼠中再次上调。从注射后第5天的差异来看，HBV可能会减少CD 1d四聚体阳性细胞的数量，增加NK细胞的数量。将腺病毒注射到GD 1基因敲除小鼠中证实了NK细胞毒性的消失。这些结果可能表明，HBV通过激活NKT细胞上调NK细胞。

Five days after intravenous injection of adenovirus expressing HBV (adeno-HBV) to BALB/c mice, serum HBsAg showed a peak whereas no elevation in adeno-GFP (control virus) injected mice during follow-up. The number of intrahepatic lymphocytes increased 1 day after injection in mice injected either adeno-HBV or adeno-GFP, suggesting that this effect is due to adenovirus itself. Howevr, 5 days after injection, the number of NK cells increased again whereas no increase in adeno-GFP injected mice. The number of CD1d tertramer positive cells decreased 1 day after injection by both adenovirus. The number of CD1d tetramer positive cells recovered in a few days in adeno-GFP injected mice. In contrast, it was not recovered until 10 days after injection of adeno-HBV. NK cytotoxicity using Yac-1 cells was up-regulated 1 day after injection of both virus. Then, it gradually went back to normal in adeno-GFP injected mice whereas iNK cytotoxicity up-regulated again in adeno-HBV injected mice. From the differences on Day 5 after injection, HBV may decrease the number of CD1d tetramer positive cells and increase the number of NK cells. Injection of adeno-HBV to GD1 knockout mice demonstrated the disappearance of NK cytotoxicity. These results may indicate that HBV up-regulated NK cells through NKT cells activation.