Tumor necrosis factor-α-induced protein-8 like-2 (TNFAIP8L2, TIPE2), a member of TNFAIP8 family, functions as a regulator in inflammation. Our previous studies showed that TIPE2 can negatively regulate HBV-specific CD8⁺ T lymphocyte functions. But the effect of TIPE2 on the apoptosis of HBV-infected hepatocytes which is very important for eliminating viruses remains unclear. Using gene expression microarray analysis, we find that TIPE2 deficiency can regulate the expression of apoptotic genes in liver tissues from HBV hydrodynamic injection (HI) mouse model. TIPE2 protein was detected in TUNEL staining positive hepatocytes in HBV-infected C57 mice. Interestingly, the TIPE2 expressed hepatocytes were just the HBV infected cells. Furthermore, TIPE2 upregulates the mRNA levels of FasL, Bim and TNFRsF1b which promote cells death, when TIPE2 was transfected into HepG2 cells in vitro. As a result, TIPE2 overexpression cells showed a higher number of apoptotic cells and increased level of cleavage caspase3 compared to controls. Those results indicate that TIPE2 participates in HBV infection by regulating apoptosis of virus-infected hepatocytes.

肿瘤坏死因子-α诱导蛋白8 like-2（TNFAIP8L2，TIPE2），是TNFAIP8家族的成员，在炎症中起调节作用。我们以前的研究表明TIPE2可以负调节HBV特异性CD8 ⁺T淋巴细胞功能。但是，对消除病毒非常重要的TIPE2对HBV感染的肝细胞凋亡的影响尚不清楚。使用基因表达微阵列分析，我们发现TIPE2缺乏可以调节HBV流体动力注射（HI）小鼠模型在肝组织中凋亡基因的表达。在HBV感染的C57小鼠的TUNEL染色阳性肝细胞中检测到TIPE2蛋白。有趣的是，表达TIPE2的肝细胞就是被HBV感染的细胞。此外，当TIPE2体外转染到HepG2细胞中时，TIPE2上调FasL，Bim和TNFRsF1b的mRNA水平，从而促进细胞死亡。。结果，与对照相比，TIPE2过表达细胞显示出更高数量的凋亡细胞，并且裂解caspase3的水平增加。这些结果表明TIPE2通过调节病毒感染的肝细胞的凋亡而参与HBV感染。