Hsp90 Activity Is Necessary for the Maturation of Rabies Virus Polymerase

Abstract

Mononegavirales is an order of viruses with a genome in the form of a non-segmented negative-strand RNA that encodes several proteins. The functional polymerase complex of these viruses is composed of two proteins: a large protein (L) and a phosphoprotein (P). The replication of viruses from this order depends on Hsp90 chaperone activity. Previous studies have demonstrated that Hsp90 inhibition results in the degradation of mononegaviruses L protein, with exception of the rabies virus, for which the degradation of P protein was observed. Here, we demonstrated that Hsp90 inhibition does not affect the expression of rabies L and P proteins, but it inhibits binding of the P protein and L protein into functional viral polymerase. Rabies and the vesicular stomatitis virus, but not the measles virus, L proteins can be expressed independently of the presence of a P protein and in the presence of an Hsp90 inhibitor. Our results suggest that the interaction of L proteins with P proteins and Hsp90 in the process of polymerase maturation may be a process specific to particular viruses.

Research Progress in RNA-Binding Proteins

“…However, RABV and other lyssaviruses have been considered as an exception from this standard scenario, as in their case, Hsp90 has been proposed to stabilise the P protein instead [10]. In this Special Dalidowska et al argue that this might not be the case [9]. The authors find, surprisingly, that the RABV L and P proteins do not require Hsp90 for intracellular accumulation, nor does the P protein seem to be necessary for L protein solubility.…”