Their presence has been accepted as an indication of an “effective cure”. However, these antibodies appear late in the disease course and so they must have a limited role in the early stages of the disease. What is the role of T-cell responses? In contrast to other viruses, there is a delayed onset, about 4–8 weeks rather than days. CD4+ T cells regulate the adaptive response, CD8+ T cells attack HBV-infected cells. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the USA National Institutes of Health (NIH),

is supporting a prospective clinical trial to investigate HBV-specific T cell responses during the course of HBV disease. There are no clear T cell differences relative to HBV genotype. The T cell responses are highest click here during acute HBV infection. During the chronic phase of HBV disease, T cell responses remain suppressed. In conclusion, there are a lot of players in the immune control of HBV infection but

their relative contributions and how they adapt to control HBV replication are still largely unknown. Andrea (Andy) Cuconati, Institute for Hepatitis & Virus Research, Pennsylvania Commonwealth Institute, PA, USA Current HBV therapy using nucleotide anti-virals has been highly effective in controlling the infection but a “cure”, as defined by HBsAg seroconversion, has remained elusive. At best after 5 years, the rate is about 25%. Other approaches are Axenfeld syndrome needed. Veliparib Myrcludex-B (see Section 6.2) is the lead entry inhibitor. NVR-1221, an encapsidation inhibitor, is entering clinical trials. In addition. studies with novel nucleotide analogues are ongoing. The HBV field has been transformed recently by the introduction of cell-based antiviral assays. Stefan Mehrle (see Section 6.2) has been leading the way. The

assay read-out will need to be optimized for high-throughput screening (HTS) but, already, the assay has shown some “hits”. A few compounds inhibited encapsidation of viral RNA. (The HBV virion contains partly double stranded (ds) DNA but the reverse-transcription from RNA to DNA occurs within the capsid.) Within the cell, HBV DNA is transported into the nucleus where the viral DNA forms covalently closed circles (cccDNA). Two specific inhibitors of cccDNA formation have been found. Current nucleotide anti-HBV compounds do give large reductions of HBV DNA in plasma but only a minimal reduction in levels of the HBs antigen (about log100.1). In contrast, one “hit”, HBF-0259 inhibited surface antigen production but not genomic replication. Structure–activity-relationship (SAR) studies have given the current lead compound, HBV-0215. In conclusion, the cell-based assay, with complete replication of HBV, has markedly improved the screening for anti-HBV compounds although further optimization is still needed to give HTS capability. Adam Zlotnick, University of Indiana, IN, USA.