The direct function of hepatitis A virus (HAV) protein 2C, a putative
NTPase, is not known, yet genetic evidence obtained from chimeric viru
ses carrying the 2C genomic region of different HAV variants indicates
that it plays a pivotal role in viral replication. In a first assessm
ent of its potential function(s), membrane and RNA binding properties
of HAV 2C were studied after expressing the protein in various recombi
nant systems. In contrast to poliovirus 2C, expression of HAV 2C was i
nhibitory to the growth and protein synthesis of bacteria. Deletion of
the N-terminal amphipathic helix of 2C abrogated this effect and the
ability of 2C to associate with eukaryotic membranes. Both, purified 2
C and the N-terminally truncated protein were shown to bind RNA in vit
ro. Our data taken together suggest that HAV 2C is a multifunctional p
rotein.