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 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)-α/β 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.
AllenL. B.,
EagleN. C.,
HuffmanJ. H.,
ShumanD. A.,
MeyerR. B.Jr,
SidwellR. W.1974; Enhancement of interferon antiviral action in L-cells by cyclic nucleotides. Proceedings of the Society for Experimental Biology and Medicine 146:580–584
BelardelliF.,
AusielloC.,
TomasiM.,
RossiG. B.1980; Cholera toxin and its B subunit inhibit interferon effects on virus production and erythroid differentiation of FLC. Virology 107:109120
BelardelliF.,
VignauxF.,
ProiettiE.,
GresserI.1984; Injection of mice with antibody to interferon renders peritoneal macrophages permissive for vesicular stomatitis and encephalomyo-carditis viruses. Proceedings of the National Academy of Sciences, U. S. A. 81:602–606
BelardelliF.,
GessaniS.,
ProiettiE.,
LocardiC.,
BorghiP.,
WatanabeY.,
KawadeY.,
GresserI.1987; Studies on the expression of spontaneous and induced interferons in mouse peritoneal cells by means of monoclonal antibodies to mouse interferons. Journal of General Virology 68:2203–2212
BenedettoA.,
RossiG. B.,
AmiciC.,
BelardelliF.,
CioèL.,
CarrubaG.,
CarrascoL.1980; Inhibition of animal virus products by means of translation inhibitors impermeable to normal cells. Virology 106:123–132
BeushausenS.,
NarindrasorasakS.,
SanwalB. D.,
DalesS.1987; In vivo and in vitro models of demyelinating disease: activation of the adenylate cyclase system influences JHM virus expression in explanted rat oligodendrocytes. Journal of Virology 61:3795–3803
BravoR.,
NeubergM.,
BurckhardtJ.,
AlmendralJ.,
WallichR.,
MullerR.1987; Involvement of common and cell type-specific pathways in c-fos gene control: stable induction by cAMP in macrophages. Cell 48:251–260
ChirgwinJ. M.,
PrzybylaA. E.,
MacDonaldR. J.,
RutterW. J.1979; Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry 18:5294–5299
Di MarzioP.,
GessaniS.,
LocardiC.,
BorghiP.,
BaglioniC.,
BelardelliF.1990; Effects of different biological response modifiers on interferon expression in bacterial lipopolysaccharide (LPS)-responsive and LPS-hyporesponsive mouse peritoneal macrophages. Journal of General Virology 71:2585–2591
FriedmanR. M.,
PastanI.1969; Interferon and cyclic-3′-5′ adenosine monophosphate: potentiation of antiviral activity. Biochemical and Biophysical Research Communications 36:735–740
GessaniS.,
BelardelliF.,
PecorelliA.,
PudduP.,
BaglioniC.1989; Bacterial lipopolysaccharide and interferon gamma induce transcription of interferon-beta mRNA and interferon secretion in murine macrophages. Journal of Virology 63:2785–2789
GresserI.,
BelardelliF.,
VignauxF.,
MauryC.,
ToveyM. G.,
MaunouryM. T.1985; Injection of mice with antibody to mouse interferon alpha/beta decreases the level of 2′-5′ oligo-adenylate synthetase in peritoneal macrophages. Journal of Virology 53:221–227
HidakaH.,
InagakiM.,
KawamotoS.,
SasakiY.1984; Isoquinolinesulfonamides, novel and potent inhibitors of cyclic nucleotide dependent protein kinase and protein kinase C. Biochemistry 23:5036–5041
KatakamiY.,
NakaoY.,
KoizumiT.,
KatakamiN.,
OgawaR.,
FujitaT.1988; Regulation of tumour necrosis factor production by mouse peritoneal macrophages: the role of cellular cyclic-AMP. Immunology 64:719–724
KorenH. S.,
HandwergerB. S.,
WunderlichJ. R.1975; Identification of macrophage-like characteristics in a cultured murine tumor line. Journal of Immunology 114:894–897
KunoS.,
VenoR.,
HayashiO.,
NakashimaH.,
HaradaS.,
YamamotoN.1986; Prostaglandin E2, a seminal constituent, facilitates the replication of acquired immune deficiency syndrome virus in vitro. Proceedings of the National Academy of Sciences, U. S. A. 83:3487–3492
LearyK. R.,
ConnorJ. R.,
MorahanP. S.1985; Comparison of herpes simplex virus type 1 DNA replication and virus production in murine bone marrow-derived and resident peritoneal macrophages. Journal of General Virology 66:1123–1129
MuschelR. J.,
RosenN.,
RosenO. M.,
BloomB. R.1977; Modulation of Fc-mediated phagocytosis by cyclic-AMP and insulin in a macrophage-like cell line. Journal of Immunology 119:1813–1820
RoeslerW. J.,
VandenbarkG. R.,
HansonR. W.1988; Cyclic AMP and the induction of eukaryotic gene transcription. Journal of Biological Chemistry 263:9063–9066
RosenN.,
PiscitelloJ.,
SchneckJ.,
MuschelR. J.,
BloomB. R.,
RosenO. M.1979; Properties of protein kinase and adenylate cyclase-deficient variants of a macrophage-like cell line. Cell Physiology 98:125–136
SantoroM. G.,
GaraciE.,
AmiciC.1991; Induction of heat shock protein synthesis by prostaglandins with anti-neoplastic and antiviral activity. In Advances in Prostaglandin, Thromboxane and Leukotriene Research pp. 867–874 Edited by
SamuelssonB.,
WongP. Y.,
SunF. F.
New York: Raven Press;
SitM. F.,
TenneyD. J.,
RothsteinJ. L.,
MorahanP. S.1988; Effect of macrophage activation on resistance of mouse peritoneal macrophages to infection with herpes simplex virus types 1 and 2. Journal of General Virology 69:1999–2010
TaffetS. M.,
SinghelK. J.,
OverholtzerJ. F.,
ShurtleffS. A.1989; Regulation of tumour necrosis factor expression in a macrophage-like cell line by lipopolysaccharide and cyclic AMP. Cellular Immunology 120:291–300
TamaokiT.,
NomotoH.,
TakahashiI.,
KatoY.,
MorimotoM.,
TomitaF.1986; Staurosporine, a potent inhibitor of phospho-lipid/Ca++ dependent protein kinase. Research Communication 135:397–402
TannbnbaumC. S.,
HamiltonT. A.1989; Lipopolysaccharide-induced gene expression in murine peritoneal macrophages is selectively suppressed by agents that elevate intracellular cAMP. Journal of Immunology 142:1274–1280
WeberJ. M.,
StewartR. B.1975; Cyclic AMP potentiation of interferon antiviral activity and effect of interferon on cellular cyclic AMP levels. Journal of General Virology 28:363–372