Hepatitis C virus infection induces elevation of CXCL10 in human brain microvascular endothelial cells

Area of Science:

• Virology
• Neuroscience
• Immunology

Background:

• Hepatitis C virus (HCV) infection is linked to extrahepatic manifestations, including neurological disease in approximately 50% of patients.
• The molecular mechanisms underlying HCV-induced neurological complications remain largely unknown.

Purpose of the Study:

• To investigate the induction of CXC chemokine ligand 10 (CXCL10) in human brain microvascular endothelial cells (HBMECs) following HCV infection.
• To explore the role of NF-κB signaling pathway in HCV-induced CXCL10 expression in HBMECs.

Main Methods:

• HCV infection of HBMECs was performed, and CXCL10 levels were measured.
• Neutralizing antibodies were used to block HCV infection.
• NF-κB activation was assessed by phosphorylation, and its inhibition was studied using specific inhibitors.
• Upregulation of IL-1 beta and IFN-gamma was also monitored.

Main Results:

• HCV infection significantly induced CXCL10 elevation in HBMECs.
• Blocking HCV infection with neutralizing antibodies abolished CXCL10 induction.
• HCV infection increased NF-κB phosphorylation (ser536) in HBMECs.
• Inhibition of NF-κB partially reduced HCV-induced CXCL10 levels and downregulated IL-1 beta and IFN-gamma.

Conclusions:

• HCV infection upregulates CXCL10 expression in HBMECs, likely mediated by NF-κB phosphorylation.
• These findings elucidate potential mechanisms of HCV-induced neuroinflammation and suggest CXCL10 as a therapeutic target.