Today, hepatitis B is geographically one of the most wide-spread of human virus epidemics. The vL-us (HBV) is transmitted by close contact and causes a variety of liver diseases, ranging from inapparent forms to acute or ful~finant hepatitis, eba-onie hepatitis and liver cirrhosis (reviewed in 56). HBV is found further in lymphoblastoid (13, 49) and pancreatic (24) cells. Perinatal HBV infection causes chronic hepatitis in more than 90 per cent of the cases (4). Moreover, those patients have approximately a 200-fold excess risk to develop hepatoeellular carcinoma (5) so that HBV is considered a causative agent for liver cancer in man. However, our understanding of HBV biology is limited, for attempts to multiply HBV in convenient experimental systems have been unsuccessful.
The Virus-How to Study Replication?The host range of HBV is apparently narrow. Only HBV-infected chimpanzees (reviewed in 15) and infected patients allow studies on HBV replication. Evidence thus has been obtained for assembly of HBV in the cy%o-plasm of cells (6) and passage through cell membrane without necessarily causing cell lysis (58). However, such investigations are expensive and time consuming, facts which induced the search for alternative approaches.One approach makes use of the HBV-related viruses ~(HV, GSHV and DHBV which infect woodchucks (55), Beechey ground squirrels (35) and 2 0. MARQUARDT Pekin ducks (40). In the DHBV system, the virus replicates via an RNA intermediate. This has recently been shown to be also the case with HBV (42). On the other hand, DHBV differs from HBV in genome organization. Furthermore, hepatocellular carcinoma has not been observed in Pekin ducks and ground squirrels. This limits the model character of these systems for HBV research.Another apprach to understand HBV replication is based on the cultivation of cells positive for HBV components. The propagation of differentiated HBV-infected hepatocytes or pancreatic cells in vitro proved to be troublesome. The interest therefore focussed on persistently HBV-infected hepatoma cell lines derived from patients (1, 3, 27) and on cell lines which have been transfected in vitro with HBV DNA (12,20,21,23,62). Whether infectious virus particles are produced by such cells remains to be demonstrated despite the detection of several virus components. The approach may nevertheless be successful since chimpanzees develop hepatitis B when their hepatocytes are inoculated with cloned HBV DNA (63). The most detailed studies of naturally persistent HBV infection have been done on the hepatoma cell line PLC/PRF/5 (3). The object of this review is to summarize the data obtained so far with this cell line and to correlate them with the virus structure and genome organization. An evaluation of the system for the understanding of HBV replication may be both possible and useful at this point.