Appl Bioinformatics 2005; 4 (4): 217-225 DATABASE REPORT 1175-5636/05/0004-0217/$34.95/0  2005 Adis Data Information BV. All rights reserved. Los Alamos Hepatitis C Immunology Database Karina Yusim, Russell Richardson, Ning Tao, Anita Dalwani, Ashish Agrawal, James Szinger, Robert Funkhouser, Bette Korber and Carla Kuiken Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, New Mexico, USA The Los Alamos Hepatitis C Virus (HCV) Sequence Database (http://hcv.lanl.gov or http://hcv-db.org) was Abstract officially launched in September 2003. The sister HCV Immunology Database was made public in September 2004. The HCV Immunology Database is based on the Human Immunodeficiency Virus (HIV) Immunology Database. The HCV Immunology Database contains a curated inventory of immunological epitopes in HCV and their interaction with the immune system, with associated retrieval and analysis tools. This article describes in detail the types of data and services that the new database offers, the tools provided and the database framework. The data and some of the HCV database tools are available for download for non-commercial use. The hepatitis C virus (HCV) has infected 4 million people in the cases, the immune response is stimulated by a specific small part US and about 170 million people worldwide. [1] Around 75% of of viral protein called an epitope. Antibodies recognise intact cases result in latent infection, [2,3] which can lead to cirrhosis and proteins, thus B-cell epitopes can be linear or conformational, liver cancer, and HCV is the leading cause of liver transplantation whereas T-cell epitopes are exclusively linear. T cells require in the US. [1] HCV-associated mortality is around one in eight, and epitope presentation by a major histocompatibility complex around one in four will develop cirrhosis of the liver. [4] With 170 (MHC), or in case of the human species, human leukocyte antigen million people infected worldwide, this means 20 million HCV-re- (HLA) class I or class II molecules. Two basic types of T cells are lated deaths in the next few decades. distinguished: cytotoxic T lymphocytes (CTLs) and T-helper cells. CTLs cause the destruction of infected cells when they bind to a There are several technical problems hampering HCV research. specific epitope-HLA molecular complex presented on the cell Both HCV drug development and vaccine studies are difficult and surface (the HLA-presenting molecule for CTL epitopes is usually expensive because of the lack of good animal models (other than a class I protein). T-helper cells produce cytokines that are impor- ethically problematic and very expensive chimpanzees), and the tant for optimal responses of B cells and antibody production or difficulty of culturing the virus in vitro. [5,6] The only effective CTL function. T-helper cells are also activated when they bind to a treatment against HCV presently is a long (6–12 months), expen- specific epitope-HLA complex on an antigen-presenting cell, but sive and highly toxic regimen of interferon and ribavirin, which is in this case the HLA-presenting molecule for T-helper cell stimu- effective in 40–80% of cases. The effectiveness of this regimen lation is generally a class II molecule. CTL generally recognise depends on the HCV genotype. For unknown reasons, the efficacy viral peptides that are processed and expressed from within an against genotype 1, most prevalent in the US, is <50%, [7] and even infected cell, whereas T-helper cells generally recognise viral lower in African Americans. [8] peptides that have been encapsulated and processed by an- An understanding of the mechanisms involved both in the tigen-presenting cells. establishment of persistent HCV infection and in the clearance of HCV infection is crucial to the design of effective therapeutic Since the isolation and characterisation of HCV in 1989, [9] a agents and vaccines against HCV. Generally, the host immune number of studies dissecting the role of different components of response against pathogens has two major arms: cellular immune protective immunity to HCV have been accumulated. Specific response comprising T cells, and humoral immune response com- anti-HCV antibodies are easily detected and constitute the basis of prising antibodies secreted by activated B lymphocytes. In both serologic diagnosis of HCV. [10] There is evidence that HCV infec-