Cyclic AMP-mediated inhibition of vesicular stomatitis virus and herpes simplex virus replication in mouse macrophage-like cells

• Published in: Journal of general virology 1992-11, Vol.73 (11), p.2949-2954
• Main Authors: Borghi, Paola, Marzio, Paola Di, Varano, Barbara, Conti, Lucia, Belardelli, Filippo, Gessani, Sandra
• Format: Article
• Language: English
• Subjects: 2',5'-Oligoadenylate Synthetase - metabolism; Animals; Biological and medical sciences; Bucladesine - pharmacology; Cells, Cultured; Cholera Toxin - pharmacology; Culture Techniques - methods; Cyclic AMP - antagonists & inhibitors; Cyclic AMP - pharmacology; Fundamental and applied biological sciences. Psychology; herpes simplex virus; Interferons - metabolism; Macrophages - microbiology; Mice; Microbiology; Protein Kinase Inhibitors; Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains; Simplexvirus - drug effects; Simplexvirus - growth & development; Vesicular stomatitis Indiana virus - drug effects; Vesicular stomatitis Indiana virus - growth & development; vesicular stomatitis virus; Viral Plaque Assay; Virology; Virus Replication - drug effects
• ISSN: 0022-1317; 1465-2099
• DOI: 10.1099/0022-1317-73-11-2949

Laboratory of Virology, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy In this study, we have analysed the effects of cAMP inducers on the multiplication of vesicular stomatis 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 P388D 1 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)- / 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 P388D 1 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 TCID 50 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. Received 17 March 1992; accepted 14 July 1992.