Download During inflammation, leukocytes tether to and roll

Hepatitis B Virus (HBV) remains a global health concern; chronic infections number in the hundreds of millions despite
the availability of a vaccine. More effective therapy may be possible by targeting the assembly of viral components into
infectious particles. In vivo, phosphorylated HBV capsid subunits assemble into capsids, protein cages that package
viral polymerase with HBV pre-genomic RNA (the single stranded RNA version of the HBV genome). Zach developed
an in vitro capsid disassembly/reassembly system to probe the assembly and RNA binding steps of HBV replication by
capsid core protein in the absence of viral polymerase. The core protein was phosphorylated and packaged less RNA
than if not phosphorylated. Nevertheless, it bound to and encapsulated both pre-genomic and heterologous (unrelated)
RNA with equally high cooperativity. Looking forward, this work provides a platform upon which drugs targeting the
processes of capsid assembly and RNA-binding can be screened, contributing significantly to ongoing rational drug
design efforts in this field.