HEAT-SHOCK PROTEINS AND VIRUS-REPLICATION - HSP70S AS MEDIATORS OF THE ANTIVIRAL EFFECTS OF PROSTAGLANDINS

Acute infection of mammalian cells with several types of RNA and DNA v iruses often results in induction of heat-shock gene expression, The p resence of hsp70 in intact virions, as well as the transient associati on of HSP with viral proteins and assembly intermediates during virus replication, has also been reported in several experimental models. Mo reover, a possible role of heat shock proteins in the beneficial effec t of fever and local hyperthermia during acute virus infection has bee n hypothesized. However, the role of HSP in virus replication remains to be defined. At the beginning of the 1980s, the use of virus models to investigate the molecular events that follow the exposure of mammal ian cells to prostaglandins led to the serendipitous discovery that sp ecific arachidonic acid derivatives are potent inhibitors of virus rep lication. This finding was rapidly followed by the observation that tr eatment of virus-infected cells with the antiviral prostaglandin A(1) (PGA(1)) resulted in the accumulation of a 70 KDa cellular protein, wh ich was identified as hsp70. It is now well established that cyclopent enone prostaglandins, which exert potent antiviral activity in several DNA and RNA virus models, induce hsp70 synthesis through cycloheximid e-sensitive activation of heat shock transcription factor. This chapte r discusses the role of heat shock proteins in the control of virus re plication and summarizes the results of our recent work, which indicat e that hsp70 is actively involved in the antiviral activity of prostag landins.