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

Abstract

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 ofdibutyryl 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)-~//] 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~ 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 TCIDso and plaque assays on Vero cells. Dibutyryl cAMP did not affect VSV binding or entry into mouse macrophages and the cAMPmediated 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.

The Adenylyl Cyclase Activator Forskolin Increases Influenza Virus Propagation in MDCK Cells by Regulating ERK1/2 Activity

“…Several studies have shown that viral replication is regulated (enhanced or inhibited) by cAMP signaling. For example, the replication of hepatitis C and human immunodeficiency viruses is enhanced by modulating cellular levels of cAMP [ 40 , 41 ]. In contrast, replication of vesicular stomatitis and herpes simplex viruses is inhibited by cAMP signaling [ 42 ].…”

Expression of the Cyclic AMP‐dependent Protein Kinase (PKA) Catalytic Subunit from a Herpes Simplex Virus Vector Extends the Survival of Rat Sympathetic Neurons in the Absence of NGF

“…Replication of HSV can be affected by CAMP. The virus has been shown to be inhibited by cAMP in macrophages (Borghi et al, 1992), while on the other hand there is an increase in permissiveness to the virus in ND cells, which are derived from the fusion of dorsal root ganglion neurons with a neuroblastoma cell line (Wheatley et al, 1992). However, since there was no difference in virus yield from neurons either with or without CPTcAMP this explanation is unlikely, and the increase in survival in stl7/PKAcat-infected cells must be due to PKAcat activity.…”