Borghi P, Di Marzio P, Varano B, Conti L, Belardelli F, Gessani S
Laboratory of Virology, Istituto Superiore di Sanità, Rome, Italy.
J Gen Virol. 1992 Nov;73 ( Pt 11):2949-54. doi: 10.1099/0022-1317-73-11-2949.
In this study, we have analysed the effects of cAMP inducers on the multiplication of vesicular stomatitis virus (VSV) and herpes simplex virus type 1 (HSV-1) in mouse macrophage-like cells. The addition of dibutyryl cAMP (dB-cAMP) or cholera toxin to resting peritoneal macrophages aged in vitro or P388D1 cells resulted in a 10- to 100-fold reduction of VSV yield compared to control cultures. In contrast, no cAMP-dependent inhibition was found in VSV-infected L929 cells. In macrophage-like cells, the dB-cAMP-induced antiviral state was not inhibited by antibodies to interferon (IFN)-alpha/beta and did not correlate with any increase in the intracellular levels of 2-5 oligo(A) synthetase. Dibutyryl cAMP did not inhibit virus yields in mouse macrophages infected with encephalomyocarditis virus. In P388D1 cells, the addition of dB-cAMP resulted in an approximately 10-fold inhibition of HSV-1 replication with respect to control cultures, as evaluated both by TCID50 and plaque assays on Vero cells. Dibutyryl cAMP did not affect VSV binding or entry into mouse macrophages and the cAMP-mediated anti-VSV state was significantly reduced by inhibitors of protein kinase C (i.e. staurosporine and H7). These data suggest that macrophages may acquire resistance to infection by VSV and HSV-1 after treatment with cAMP inducers. This cAMP-mediated antiviral activity does not depend on the modulation of the endogenous IFN system, suggesting that macrophages exhibit multiple resistance mechanisms (i.e. IFN-dependent and IFN-independent) to maintain their intrinsic antiviral activity.
在本研究中，我们分析了环磷酸腺苷（cAMP）诱导剂对水泡性口炎病毒（VSV）和1型单纯疱疹病毒（HSV-1）在小鼠巨噬细胞样细胞中增殖的影响。将二丁酰环磷酸腺苷（dB-cAMP）或霍乱毒素添加到体外老化的静息腹膜巨噬细胞或P388D1细胞中，与对照培养物相比，VSV产量降低了10至100倍。相比之下，在VSV感染的L929细胞中未发现cAMP依赖性抑制作用。在巨噬细胞样细胞中，dB-cAMP诱导的抗病毒状态不受α/β干扰素（IFN）抗体的抑制，并且与2-5寡聚腺苷合成酶细胞内水平的任何增加均无相关性。二丁酰环磷酸腺苷不会抑制感染脑心肌炎病毒的小鼠巨噬细胞中的病毒产量。在P388D1细胞中，添加dB-cAMP相对于对照培养物导致HSV-1复制受到约10倍的抑制，这通过对Vero细胞进行的半数组织培养感染剂量（TCID50）和空斑试验进行评估。二丁酰环磷酸腺苷不影响VSV与小鼠巨噬细胞的结合或进入，并且蛋白激酶C抑制剂（即星形孢菌素和H7）可显著降低cAMP介导的抗VSV状态。这些数据表明，巨噬细胞在用cAMP诱导剂处理后可能获得对VSV和HSV-1感染的抗性。这种cAMP介导的抗病毒活性不依赖于内源性IFN系统的调节，这表明巨噬细胞表现出多种抗性机制（即IFN依赖性和IFN非依赖性）以维持其固有的抗病毒活性。
