de Marco A, Carattoli A, Rozera C, Fortini D, Giorgi C, Belardo G, Amici C, Santoro M G
Department of Biology, University of Rome Tor Vergata, Italy.
Eur J Biochem. 1998 Sep 1;256(2):334-41. doi: 10.1046/j.1432-1327.1998.2560334.x.
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.
环戊烯酮前列腺素可抑制包括逆转录病毒在内的多种DNA和RNA病毒的复制。这种抗病毒活性与通过激活受感染细胞中的热休克转录因子（HSF）诱导70 kDa热休克蛋白（HSP70）有关。在本研究中，我们调查了前列腺素A1（PGA1）对人免疫缺陷病毒1型（HIV-1）急性感染期间CEM-SS细胞中HSP70基因表达调控以及病毒RNA和蛋白质合成的影响。我们报告称，HIV-1感染不会改变PGA1对HSF的激活作用，然而，由于HSP70 mRNA稳定性增强，它会导致细胞内HSP70 mRNA水平升高。我们还表明，正如在不同病毒/宿主细胞模型研究中所报道的那样，PGA1在HIV-1感染期间通过在多个水平发挥作用来抑制HIV-1复制。除了先前报道的对HIV-1 mRNA转录的阻断作用外，还发现PGA1可抑制病毒蛋白质合成。这些结果，连同前列腺素在临床上用于治疗多种疾病这一事实，为寻找新型抗逆转录病毒药物开辟了新的前景。
