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 viruses often results in induction of heat-shock gene expression. The presence of hsp70 in intact virions, as well as the transient association of HSP with viral proteins and assembly intermediates during virus replication, has also been reported in several experimental models. Moreover, a possible role of heat shock proteins in the beneficial effect of fever and local hyperthermia during acute virus infection has been 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 mammalian cells to prostaglandins led to the serendipitous discovery that specific arachidonic acid derivatives are potent inhibitors of virus replication. This finding was rapidly followed by the observation that treatment of virus-infected cells with the antiviral prostaglandin A1 (PGA1) resulted in the accumulation of a 70 KDa cellular protein, which was identified as hsp70. It is now well established that cyclopentenone prostaglandins, which exert potent antiviral activity in several DNA and RNA virus models, induce hsp70 synthesis through cycloheximide-sensitive activation of heat shock transcription factor. This chapter discusses the role of heat shock proteins in the control of virus replication and summarizes the results of our recent work, which indicate that hsp70 is actively involved in the antiviral activity of prostaglandins.
Santoro
M G
MG
Institute of Experimental Medicine, CNR, Rome, Italy.
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D005334:Fever / Q000821:virology; D018840:HSP70 Heat-Shock Proteins / Q000502:physiology*; D006801:Humans; D011453:Prostaglandins / Q000494:pharmacology*; D014764:Viral Proteins / Q000378:metabolism; D014777:Virus Diseases / Q000378:metabolism; D014779:Virus Replication
D000998:Antiviral Agents; D018840:HSP70 Heat-Shock Proteins; D011453:Prostaglandins; D014764:Viral Proteins