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

BALB/c小鼠静脉注射表达HBV腺病毒(Adeno-HBV5天)后，血清HBs Ag出现高峰，而注射Adeno-GFP(对照病毒)的小鼠在随访期间无明显升高。注射Adeno-HBV或Adeno-GFP的小鼠在注射后1天，肝内淋巴细胞数量增加，这表明这种作用是由腺病毒本身造成的。然而，注射后第5天，注射Adeno-GFP的小鼠的NK细胞数量再次增加，而没有增加。注射后1d，CD1d三聚体阳性细胞数明显减少。注射Adeno-GFP的小鼠CD1d四聚体阳性细胞数在几天内恢复。而注射Adeno-HBV10天后才恢复正常。两种病毒接种后1d，Yac-1细胞对NK细胞的杀伤活性均上调。随后，Adeno-GFP注射组小鼠的细胞毒性逐渐恢复正常，而Adeno-HBV腺病毒注射组小鼠的墨汁细胞毒性再次上调。从注射后第5天的差异来看，乙肝病毒可降低CD1d四聚体阳性细胞数，增加NK细胞数。Gd1基因敲除小鼠注射Adeno-HBV腺病毒后，NK细胞毒性消失。这些结果可能表明，乙肝病毒通过激活NKT细胞来上调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.