Visualizing hepatitis C virus infection in humanized mice

• Chronic hepatitis C remains a major global health problem.
• HCV has a narrow host range limited to humans and chimpanzees.
• Humanized mice offer unique opportunities to dissect HCV infection in vivo.
• Low HCV antigen load and high autofluorescence in the liver pose challenges to visualize HCV infection.
• Novel reporters facilitate reliable detection of HCV infection in situ.

Hepatitis C virus (HCV) establishes frequently persistent infections. Chronic carriers can develop severe liver disease. HCV has been intensely studied in a variety of cell culture systems. However, commonly used cell lines and primary hepatocyte cultures do not or only in part recapitulate the intricate host environment HCV faces in the liver. HCV infects readily only humans and chimpanzees, which poses challenges in studying HCV infection in vivo. Consequently, tractable small animal models are needed that are not only suitable for analyzing HCV infection but also for testing novel therapeutics. Here, we will focus our discussion on humanized mice, i.e. mice engrafted with human tissues or expressing human genes, which support HCV infection. We will further highlight novel methods that can be used to unambiguously detect HCV infected cells in situ, thereby facilitating a spatio-temporal dissection of HCV infection in the three dimensional context of the liver.