Regulation of molecular chaperones by a human virus

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DESCRIPTION (provided by applicant): Virus replication requires the redirection of host biochemistry to synthesize, fold and assemble viral proteins into progeny virions. While the expression and redistribution of heat shock proteins (HSPs) has been extensively studied in the context of the cellular heat shock response, studies on adenovirus infection demonstrate selective induction of specific HSPs. Heat shock genes appear to participate in virus infection as virus mutants incapable of inducing the expression of HSPs are replicative defective, an effect that can be overcome by heat shock or heterologous expression of specific HSPs. In order to elucidate the molecular basis for chaperone dependence of viral replication, we will identify and characterize the specific HSPs and chaperone networks induced in response to viral replication and examine the contribution of HSF1 transcription factor in viral specific HSP gene induction. Using an RNA interference approach, we will examine the mechanistic contribution of these chaperones to adenovirus replication. Finally, we propose to establish the relationship between chaperone recruitment to sites of virus replication and cellular protein quality control to better understand the regulation of chaperone-dependent functions by viruses.