Persistent hepatitis C virus infection in microscale primary human hepatocyte cultures

Alexander Ploss, Salman R. Khetani, Christopher T. Jones, Andrew J. Syder, Kartik Trehan, Valeriya A. Gaysinskaya, Kathy Mu, Kimberly Ritola, Charles M. Rice, Sangeeta N. Bhatia

Research output: Contribution to journalArticlepeer-review

161 Scopus citations

Abstract

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 as extrahepatic complications such as cryoglobulinemia and lymphoma. Preventative and therapeutic options are severely limited; there is no HCV vaccine available, and nonspecific, IFN-based treatments are frequently ineffective. Development of targeted antivirals has been hampered by the lack of robust HCV cell culture systems that reliably predict human responses. Here, we show the entire HCV life cycle recapitulated in micropatterned cocultures (MPCCs) of primary human hepatocytes and supportive stroma in a multiwell format. MPCCs form polarized cell layers expressing all known HCV entry factors and sustain viral replication for several weeks. When coupled with highly sensitive fluorescence- and luminescence-based reporter systems, MPCCs have potential as a high-throughput platform for simultaneous assessment of in vitro efficacy and toxicity profiles of anti-HCV therapeutics.

Original languageEnglish (US)
Pages (from-to)3141-3145
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number7
DOIs
StatePublished - Feb 16 2010

All Science Journal Classification (ASJC) codes

  • General

Keywords

  • Drug development
  • Infection
  • Liver
  • Tissue engineering
  • Viral hepatitis

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