U.S. Department of Health and Human Services

Liver Diseases Virology Section

T. Jake Liang, M.D., Chief

About the Section

The Liver Diseases and Virology Section focuses on various topics regarding liver disease related to virus infection.

Current Research

The section’s research interests include: molecular pathogenesis of hepatitis B and C virus infection; mechanisms of viral hepatocarcinogenesis; viral and innate immunobiology of viral hepatitis; molecular strategies for vaccine and antiviral development; and animal models of liver diseases. Infection with hepatitis B and C viruses (HBV and HCV, respectively) affects more than 10 percent of the world population. These infections are the most common etiology of chronic liver disease and hepatocellular carcinoma, which is the fourth leading cause of death from cancer in the world. Current therapies for both viruses are less than optimal. Although an effective vaccine for HBV is available, the prospect for a HCV vaccine remains elusive. To develop and implement effective prophylactic vaccines and better therapeutic regimens, scientists must understand: the viral life cycle, viral mechanisms for productive and persistent infection, virus-host interactions, and host immune responses. Research in this section studies these topics at the molecular, cellular and genetic levels.

Although many gaps in our knowledge of HCV exist, researchers have made great strides in characterizing the virus and functions of viral genes. They have also described the replication pathway and immunologic mechanisms of liver injury. Unlike other RNA viruses, HCV has a high propensity to cause persistent infection despite an active host immune response. Thus, it possesses unique mechanisms to counteract the various host defenses. HCV gene products have been shown to interact with many host factors and to induce cellular alterations vital for viral replication, persistence, and pathogenesis. The development of in vitro systems, including infectious cell cultures, affords the opportunity to fully characterize viral replication and virus-cell interactions. SCID/uPA mice transplanted with human hepatocytes susceptible to HCV infection and transgenic mouse models are useful as small animal models. Researchers in this section have taken three approaches to study HCV infection and pathogenesis:  (1) understanding the mechanisms of action of interferon, ribavirin, and the new class of direct-acting antivirals in HCV therapy and exploring the biological basis of treatment non-response with the goal of improving current treatment regimen; (2) applying molecular, biochemical, and functional genomic tools to identify and characterize structural and functional interactions among the virus, viral gene products, and the host; (3) generating novel reagents and tools for developing and evaluating vaccines and antivirals by building and improving on currently available model systems; and (4) developing novel therapeutics to treat HCV infection.

For HBV, scientists have studied the replication and virus-host interactions in great detail and have described many of the pathways. The availability of culture systems and small animal models has greatly facilitated the elucidation of fundamental knowledge of the virus and the evaluation of vaccine and therapeutic candidates. Although the various virologic functions in replication are well known, the roles of interacting cellular factors remain largely undefined. In addition, the viral and host functions for productive and persistent infection in vivo are poorly understood.

Research in the section has focused on understanding the functions of HBX—a viral gene product and accessory protein that is not essential for replication in vitro but appears important for viral infection in vivo. Another area of focus is developing therapeutic strategy targeting this important viral function. We are also applying our overall approach in functional genomics described above for HCV to studying HBV-host interactions.

Specific projects concentrate on: studying hepatitis C virology and host dependencies through functional genomics approaches (Qisheng Li, Staff Scientist, Cameron Schweitzer); investigating the mechanisms of HCV entry and novel HCV inhibitors (Zongyi Hu, Staff Scientist); using stem cells-derived hepatocytes for studying HCV infection (Arnaud Carpentier, Postdoctoral Fellow and Qisheng Li, Staff Scientist); examining the relationship between the hepatitis C virus and the lipid metabolism of the infected cells (Qisheng Li, Staff Scientist); describing the mechanisms of interferon in HCV infection and mechanisms of innate immune response (Rui Li and Fang Zhang, Visiting Fellows); developing innovative therapeutics in HCV infection (Zongyi Hu, Staff Scientist and Melissa He, Visiting Fellow); studying the molecular biology of hepatitis B and C viruses (Zhensheng Zhang, Biologist); understanding the relevance of type III interferon’s in hepatitis C virus infection (Fang Zhang, Visiting Fellow).

The purpose and goal of our research is to develop a better understanding and improve treatment of viral liver diseases.