SARS-CoV-2 spike protein enhances HBV replication via autophagy and aggravates inflammation in CHB patients with liver dysfunction

This study investigated the effects of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein (S protein) on hepatitis B virus (HBV) replication and immune function in patients with chronic hepatitis B (CHB), aiming to elucidate the underlying mechanisms of S protein–HBV interaction. Through in vitro cell experiments and clinical sample analyses, S protein expression was induced in HepG2.2.15 cells, leading to enhanced HBV replication; this effect was reduced by autophagy inhibitors, confirming the critical mediating role of autophagy. Furthermore, peripheral blood mononuclear cells (PBMCs) from CHB patients were co-cultured with the S protein, resulting in increased inflammatory responses in T cells and monocytes, particularly in patients with concurrent abnormal liver function and lipid metabolism disorders. In summary, the S protein promotes HBV replication by activating autophagy and exacerbates immune inflammation in CHB patients. Autophagy inhibitors block its effect on HBV replication, suggesting autophagy as a key regulatory target. The immune-activating effects of the S protein are more pronounced in patients with liver dysfunction and metabolic abnormalities. These findings provide a basis for further investigation into the interplay between the S protein and autophagy in HBV infection.