INDUCTION OF INTRACELLULAR MEMBRANE REARRANGEMENTS BY HAV PROTEINS 2CAND 2BC

Hepatitis A virus (HAV) is distinguished from other picornaviruses by its slow and relatively poor, noncytopathic growth in cultures of mamm alian cells. The 2C and 2BC proteins of HAV have been implicated in th e determination of virus growth in cultured cells. The homologous prot eins from other picornaviruses, such as poliovirus, have been demonstr ated to exhibit multiple activities, such as RNA binding, nucleotide b inding and NTPase, and membrane binding and reorganization. At least s ome of these activities are required for viral RNA replication. We rep ort here that HAV 2C and 2BC proteins, like their poliovirus counterpa rts, can induce rearrangement of intracellular membranes and directly or indirectly interact with membranes. Therefore, the inefficient repl ication properties of HAV are not consequences of the inherent ability of 2C (2BC) to interact with membranes. The effect of 2C (2BC) protei n sequences derived from a cell culture-adapted (cc) strain of HAV was compared with that of corresponding protein sequences from either a w ild-type (wt) strain of HAV or a faster replicating cytopathic (cp) st rain. The analysis demonstrated that mutations acquired in wt virus du ring adaptation to cell culture do not change dramatically either the ability of these proteins to associate with membranes and induce membr ane alterations or the specific architecture of the induced membrane s tructures. On the other hand, 2C, hut not 2BC, protein from the cp str ain of HAV induced different membrane structures. (C) 1997 Academic Pr ess.