Immunization with lentiviral vector‑modified dendritic cells encoding ubiquitinated hepatitis B core antigen promotes Th1 differentiation and antiviral immunity by enhancing p38 MAPK and JNK activation in HBV transgenic mice.

Abstract

Hepatitis B virus (HBV) infection is a global public health problem. T helper (Th)1‑associated cytokines are involved in HBV clearance during acute and persistent infection. In our previous study, it was demonstrated that lentiviral vectors encoding ubiquitinated hepatitis B core antigen (LV‑Ub‑HBcAg) effectively transduced dendritic cells (DCs) to induce maturation, which promoted T cell polarization to Th1 and generated HBcAg‑specific cytotoxic T lymphocytes (CTLs) exvivo. In the present study, HBV transgenic mice were immunized with LV‑Ub‑HBcAg‑transduced DCs and HBcAg‑specific immune responses were evaluated. Cytokine expression was analyzed by ELISA. T lymphocyte proliferation was detected with a Cell Counting Kit‑8 assay and HBcAg‑specific CTL activity was determined using a lactate dehydrogenase release assay. The expression levels of p38‑mitogen‑activated protein kinase (p38‑MAPK), phosphorylated (p)‑p38MAPK, c‑Jun N‑terminal kinase (JNK) and p‑JNK were detected by western blot analysis. The results demonstrated that LV‑Ub‑HBcAg‑transduced DCs significantly increased the Th1/Th2 cytokine ratio, and effectively reduced the levels of serum hepatitis B surface antigen (HBsAg), HBV DNA, and liver HBsAg and HBcAg. Furthermore, the LV‑Ub‑HBcAg‑transduced DCs upregulated the expression of p‑P38‑MAPK and p‑JNK in T lymphocytes. In conclusion, the present study indicated that LV‑Ub‑HBcAg‑transduced DCs generated predominant Th1 responses and enhanced CTL activity in HBV transgenic mice. Activation of the P38‑MAPK/JNK signaling pathway may be involved in this induction.