Activation of heat-shock response by an adenovirus is essential for virus replication

Successful viral infection requires viruses to redirect host biochemistry t o replicate the viral genome, and produce and assemble progeny virions. Cel lular heat-shock responses, which are characterized as elevation and reloca lization of heat-shock proteins, occur during replication of many viruses(1 -7). Such responses might be host reactions to the synthesis of foreign pro tein, or might be irrelevant consequences of the viral need to activate tra nscription. Alternatively, as heat-shock proteins can facilitate protein fo lding(8,9), activating a heat-shock response might be a specific virus func tion ensuring proper synthesis of viral proteins and virions. It is not pos sible to determine whether heat-shock response is essential for virus repli cation, because the implicated viral genes (such as Ad5 E1A, ref. 10) also control other essential replication steps. Here we report that expression o f Gam1, a protein encoded by the avian virus CELO (ref. 11), elevates and r elocalizes hsp70 and hsp40. Gam1-negative CELO is replication-defective; ho wever, Gam1 function can be partially replaced by either heat shock or forc ed hsp40 expression. Thus, an essential function of Gam1 during virus repli cation is to activate host heat-shock responses with hsp40 as a primary tar get.