The non-structural 5A protein of hepatitis C virus

The non-structural (NS) 5A protein of hepatitis C virus (HCV) is cleaved, a fter translation, by the NS3-encoded zinc-dependent serine proteinase, from the NS4B protein upstream and the NS5B protein downstream. The released, m ature NS5A protein is a 56 000 MW phosphoprotein (p56), which also exists w ithin infected cells in a hyperphosphorylated form (p58). The NS5A gene has a quasispecies distribution, meaning that various NS5A sequences co-exist, in various proportions, in infected individuals. HCV NS5A appears to be lo cated in cytoplasmic membranes surrounding the nucleus, Its precise functio ns are not known, HCV non-structural proteins, including NS5A, form a large multiprotein replication complex, which probably directs the replication o f the HCV genome. HCV NS5A lacking the 146 N-terminal amino acids is a pote nt transcriptional activator in vitro. NS5A can also bind to single-strand RNA-dependent protein kinase (PKR) and inhibit its antiviral function, An ' interferon (IFN) sensitivity-determining region' has recently been postulat ed in the NS5A protein central region in hepatitis C virus (HCV) genotype I b, but strongly conflicting evidence has been published, In fact, there wou ld seem to be no such region in the NS5A protein, even though NS5A plays an important and complex role in HCV resistance to IFN. Structure-function st udies are required to identify precisely how NS 5A and IFN interact.