Induction of RANTES/CCL5 by herpes simplex virus is regulated by nuclear factor κB and interferon regulatory factor 3

Abstract

Short CommunicationInduction of RANTES/CCL5 by herpes simplex virus is regulated by nuclear factor kB and interferon regulatory factor 3 Chemokines regulate migration of leukocytes to sites of infection. In this work, we have shown that the chemokine RANTES/CCL5 is produced after herpes simplex virus (HSV) infection of macrophages and fibroblasts and provide data on the underlying molecular mechanism. Reporter gene assays showed HSV-induced RANTES production to be regulated at the transcriptional level. Expression of RANTES was blocked by N-tosyl-L-phenylalanine, an inhibitor of the nuclear factor kB (NF-kB) pathway and also in cell lines stably expressing a dominant-negative mutant of IkB kinase b. Cell lines stably expressing a dominant-negative mutant of interferon regulatory factor 3 (IRF-3) also produced dramatically decreased levels of RANTES after infection compared with the control cell line. In contrast, overexpression of dominant-negative p38 and also treatment with SB203580, an inhibitor of p38, did not significantly affect expression of RANTES. Taken together, these data suggest that HSV induces transcriptional activation of the RANTES gene through the transcription factors NF-kB and IRF-3.

Sphingosine Kinase 1 Regulates Tumor Necrosis Factor-mediated RANTES Induction through p38 Mitogen-activated Protein Kinase but Independently of Nuclear Factor κB Activation

“…The p38 MAPK pathway is a well known component of TNF signaling (46,47) and can also be regulated by SK1 (48 -50). Furthermore, this pathway can also affect chemokine expression, although the effects on RANTES vary depending on the cell type and stimulus (34,51,52). Consequently, as a first step, the role of p38 MAPK in RANTES regulation was determined utilizing the p38 MAPK inhibitor BIRB 796 (53).…”

Viral Activation of Macrophages through TLR-Dependent and -Independent Pathways

“…The protocol for RANTES ELISA was described earlier (32). For measurement of TNF-␣ an ELISA duoset from R&D Systems (catalogue no.…”

“…RANTES expression requires the transcription factors NF-B and IRF-3 and is dependent on a functional viral genome (3,32). TNF-␣ induction, which is only partly sensitive to UV treatment of the virus, requires NF-B and activating transcription factor 2/Jun (6,33).…”

Induction of interleukin-6 in human retinal epithelial cells by an attenuated Herpes simplex virus vector requires viral replication and NFκB activation

“…In C33 cells, infection by HSV-1 with mutations in ICP-4 or ICP-27 did not activate NF-κB (Patel et al 1998). In macrophages, where NF-κB activation was required for induction of RANTES, deletion of the ICP-0 gene prevented induction whereas deletion of ICP-4, ICP-27, and ICP-22 had no effect (Melchjorsen et al 2002;Melchjorsen and Paludan 2003). In contrast, ICP-27 appears to be required for NF-κB activation in Hep-2 and CV-1 cells (Goodkin et al 2003;Hargett et al 2006).…”