Induction of the heat-shock response by antiviral prostaglandins in human cells infected with human immunodeficiency virus type 1.
Cyclopentenone prostaglandins inhibit the replication of several DNA and RNA viruses, including retroviruses. The antiviral activity has been associated with the induction of a 70-kDa heat-shock protein (HSP70), via activation of the heat-shock transcription factor (HSF) in infected cells. In the present study we investigated the effect of prostaglandin A1 (PGA1) on the regulation of HSP70 gene expression as well as on viral RNA and protein synthesis in CEM-SS cells during acute infection with human immunodeficiency virus type 1 (HIV-1). We report that HIV-1 infection does not alter HSF activation by PGA1, whereas it causes an increase in intracellular HSP70 mRNA levels, as a result of enhanced HSP70 mRNA stability. We also show that, as reported in studies of different virus/host cell models, PGA1 inhibits HIV-1 replication by acting at multiple levels during HIV-1 infection. In addition to the previously reported block of HIV-1 mRNA transcription, PGA1 was also found to inhibit viral protein synthesis. These results, together with the fact that prostaglandins are used clinically in the treatment of several diseases, open new perspectives in the search for novel antiretroviral drugs.
Department of Biology, University of Rome Tor Vergata, Italy.
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de Marco
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Carattoli
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Rozera
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Fortini
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Giorgi
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Belardo
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Amici
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Santoro
D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism; D015967:Gene Expression Regulation, Viral / Q000187:drug effects*; D015658:HIV Infections / Q000821:virology*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D000076249:Heat Shock Transcription Factors; D006801:Humans; D011454:Prostaglandins A / Q000494:pharmacology* / Q000627:therapeutic use; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects; D012367:RNA, Viral / Q000378:metabolism; D015682:Retroviridae Proteins, Oncogenic / Q000378:metabolism; D014157:Transcription Factors; D015533:Transcriptional Activation / Q000235:genetics; D014764:Viral Proteins / Q000378:metabolism
D000998:Antiviral Agents; D004268:DNA-Binding Proteins; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D011454:Prostaglandins A; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D012367:RNA, Viral; D015682:Retroviridae Proteins, Oncogenic; D014157:Transcription Factors; D014764:Viral Proteins; C060954:p24 protein, Human T-lymphotropic virus 1; C100573:prostaglandin A1