{Reference Type}: Journal Article
{Title}: The nuclear matrix protein HNRNPU restricts hepatitis B virus transcription by promoting OAS3-based activation of host innate immunity.
{Author}: Zeng Q;Ren Y;Wang Y;Yang J;Qin Y;Yang L;Zheng X;Huang A;Fan H;
{Journal}: J Med Virol
{Volume}: 96
{Issue}: 7
{Year}: 2024 Jul
{Factor}: 20.693
{DOI}: 10.1002/jmv.29805
{Abstract}: Heterogeneous nuclear protein U (HNRNPU) plays a pivotal role in innate immunity by facilitating chromatin opening to activate immune genes during host defense against viral infection. However, the mechanism by which HNRNPU is involved in Hepatitis B virus (HBV) transcription regulation through mediating antiviral immunity remains unknown. Our study revealed a significant decrease in HNRNPU levels during HBV transcription, which depends on HBx-DDB1-mediated degradation. Overexpression of HNRNPU suppressed HBV transcription, while its knockdown effectively promoted viral transcription, indicating HNRNPU as a novel host restriction factor for HBV transcription. Mechanistically, HNRNPU inhibits HBV transcription by activating innate immunity through primarily the positive regulation of the interferon-stimulating factor 2'-5'-oligoadenylate synthetase 3, which mediates an ribonuclease L-dependent mechanism to enhance innate immune responses. This study offers new insights into the host immune regulation of HBV transcription and proposes potential targets for therapeutic intervention against HBV infection.