The role of HMGB1 in the pathogenesis of acute or chronic viral illnesses remains elusive. As mentioned, HMGB1 can escape extracellularly upon necrotic cell death. West Nile encephalitis and acute hepatitis are viral-induced pathologies associated with necrotic cell death either via direct cytotoxic effects of the virus itself or the inflammatory response to viral infection (36) . In a recent study utilizing hepatitis B virus (HBV) transgenic mice injected with virus specific cytotoxic T lymphocytes (CTLs), HMGB1 translocates from the nucleus to the cytoplasm of hepatocytes surrounding CTLcontaining necroinflammatory foci. Furthermore, treatment with HMGB1 inhibitors in this model significantly decreases the recruitment of inflammatory cells (117) .