H epatitis B virus (HBV) is a small enveloped DNA virus and causes chronic infection of the liver that often leads to chronic hepatitis, cirrhosis, and hepatocellular carcinoma. [1][2][3][4] The lack of a practical small animal model has impeded the study of the biology of this virus and the development of effective antiviral therapies. Chimpanzee is the only natural host that allows active replication of HBV. [5][6][7] Although this animal is a valuable model for the study of hepatitis viruses, 8 the practical use of chimpanzees is severely limited both ethically and economically.Several small animal models of HBV infection have been reported. The HBV transgenic mouse is a very useful model for the study of virology and evaluation of antiviral drugs. [9][10][11][12] However, the liver cells of this model are not permissive for HBV infection; therefore, studying virus-cell interactions such as receptor binding and entry is not possible. The HBVtrimera mouse is another useful mouse model. 13 In this model, ex vivo HBV-infected human liver fragments are implanted into lethally irradiated mice after SCID mouse bone marrow transplantation. Approximately 80% of the mice develop viremia 2 to 3 weeks after infection. However, the rate of positivity subsequently decreases to less than 20% 6 weeks after infection. The level viremia is approximately 10 5 copies/mL. More recently, HBV-containing human serum samples were used to infect human hepatocyte repopulated mice. 14 A high-level viremia (4.5 and 10 ϫ 10 8 copy/ mL) and HBs antigenemia are observed 8 weeks after injection. This mouse model is promising because HBV replicates in natural host cells, human hepatocytes. However,
Following genomics and proteomics, cytomics, a novel method of looking at life, has emerged for analyzing large populations of cells on a single-cell basis with multiple parameters in a quantitative manner. We have developed a highly integrated live-cell microarray system for analyzing the cellular responses of individual cells using a microwell array chip that has 234,000 microwells each of which is just large enough to fit a single cell. Compared with flow cytometry and microscope-based methods, our system can analyze the history of the cellular responses of a large number of cells. We have successfully applied the system to analyze human antigen-specific B-cells and produced human monoclonal antibodies (MoAb) against hepatitis B virus surface antigen. We have also constructed a mouse system to assess hepatitis B virus-neutralization activity and have demonstrated the neutralization activity of our antibodies. Our technology should expand the horizons of cell analysis as well as enable generation of human MoAb for antibody-based therapeutics and diagnosis for infectious diseases such as hepatitis viruses. '
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.