Citation: Xi Zhang, Yuanyuan Li, Chen Huan, Yubao Hou, Rujia Liu, Hongyun Shi, Peng Zhang, Baisong Zheng, Yingchao Wang, Hong Wang, Wenyan Zhang. LncRNA NKILA inhibits HBV replication by repressing NF-κB signalling activation .VIROLOGICA SINICA, 2024, 39(1) : 44-55.  http://dx.doi.org/10.1016/j.virs.2023.10.002

LncRNA NKILA inhibits HBV replication by repressing NF-κB signalling activation

  • Hepatitis B virus (HBV) infection results in liver cirrhosis and hepatocellular carcinoma (HCC). HBx/nuclear factor (NF)-κB pathway plays a role in HBV replication. However, whether NF-κB-interacting long noncoding RNA (NKILA), a suppressor of NF-κB activation, regulates HBV replication remains largely unknown. In this study, gain-and-loss experiments showed that NKILA inhibited HBV replication by inhibiting NF-κB activity. In turn, HBV infection down-regulated NKILA expression. In addition, expression levels of NKILA were lower in the peripheral blood-derived monocytes (PBMCs) of HBV-positive patients than in healthy individuals, which were correlated with HBV viral loads. And a negative correlation between NKILA expression level and HBV viral loads was observed in blood serum from HBV-positive patients. Lower levels of endogenous NKILA were also observed in HepG2 cells expressing a 1.3-fold HBV genome, HBV-infected HepG2-NTCP cells, stable HBV-producing HepG2.2.15 and HepAD38 cells, compared to those HBV-negative cells. Furthermore, HBx was required for NKILA-mediated inhibition on HBV replication. NKILA decreased HBx-induced NF-κB activation by interrupting the interaction between HBx and p65, whereas NKILA mutants lack of essential domains for NF-κB inhibition, lost the ability to inhibit HBV replication. Together, our data demonstrate that NKILA may serve as a suppressor of HBV replication via NF-κB signalling.

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    LncRNA NKILA inhibits HBV replication by repressing NF-κB signalling activation

      Corresponding author: Yingchao Wang, wangyingc@jlu.edu.cn
      Corresponding author: Hong Wang, wanghong_2020@jlu.edu.cn
      Corresponding author: Wenyan Zhang, zhangwenyan@jlu.edu.cn
    • a. Department of Infectious Diseases, Center of Infectious Diseases and Pathogen Biology, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, The First Hospital of Jilin University, Changchun, 130012, China;
    • b. Institute of Virology and AIDS Research, The First Hospital of Jilin University, Changchun, 130012, China;
    • c. Department of Ophthalmology, The First Hospital of Jilin University, Changchun, 130012, China;
    • d. Hepatobiliary Pancreatic Surgery, The First Hospital of Jilin University, Changchun, 130012, China

    Abstract: Hepatitis B virus (HBV) infection results in liver cirrhosis and hepatocellular carcinoma (HCC). HBx/nuclear factor (NF)-κB pathway plays a role in HBV replication. However, whether NF-κB-interacting long noncoding RNA (NKILA), a suppressor of NF-κB activation, regulates HBV replication remains largely unknown. In this study, gain-and-loss experiments showed that NKILA inhibited HBV replication by inhibiting NF-κB activity. In turn, HBV infection down-regulated NKILA expression. In addition, expression levels of NKILA were lower in the peripheral blood-derived monocytes (PBMCs) of HBV-positive patients than in healthy individuals, which were correlated with HBV viral loads. And a negative correlation between NKILA expression level and HBV viral loads was observed in blood serum from HBV-positive patients. Lower levels of endogenous NKILA were also observed in HepG2 cells expressing a 1.3-fold HBV genome, HBV-infected HepG2-NTCP cells, stable HBV-producing HepG2.2.15 and HepAD38 cells, compared to those HBV-negative cells. Furthermore, HBx was required for NKILA-mediated inhibition on HBV replication. NKILA decreased HBx-induced NF-κB activation by interrupting the interaction between HBx and p65, whereas NKILA mutants lack of essential domains for NF-κB inhibition, lost the ability to inhibit HBV replication. Together, our data demonstrate that NKILA may serve as a suppressor of HBV replication via NF-κB signalling.

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