Persistent hepatitis C virus infection in microscale primary human hepatocyte cultures

• DOI: 10.1073/pnas.0915130107
• Publication Date: 2010-02-02T03:51:30Z
• Authors: Alexander Ploss; Salman R. Khetani; Christopher T. Jones; Andrew J. Syder; Kartik Trehan; Valeriya A. Gaysi...; Kathy Mu; Kimberly Ritola; Charles M. Rice; Sangeeta N. Bhatia
• Keywords: Hepatitis C

Hepatitis C virus (HCV) remains a major public health problem, affecting approximately 130 million people worldwide. HCV infection can lead to cirrhosis, hepatocellular carcinoma, and end-stage liver disease, as well extrahepatic complications such cryoglobulinemia lymphoma. Preventative therapeutic options are severely limited; there is no vaccine available, nonspecific, IFN-based treatments frequently ineffective. Development of targeted antivirals has been hampered by the lack robust cell culture systems that reliably predict human responses. Here, we show entire life cycle recapitulated in micropatterned cocultures (MPCCs) primary hepatocytes supportive stroma multiwell format. MPCCs form polarized layers expressing all known entry factors sustain viral replication for several weeks. When coupled with highly sensitive fluorescence- luminescence-based reporter systems, have potential high-throughput platform simultaneous assessment vitro efficacy toxicity profiles anti-HCV therapeutics.