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* Department of Rheumatology and Inflammation Research, Göteborg University, Göteborg, Sweden; and
CEA-Grenoble, Grenoble, France
We have recently identified a peptide derived from the secreted portion of the HSV-2 glycoprotein G, gG-2p20, to be proinflammatory. Based on its ability to activate neutrophils and monocytes via the formyl peptide receptor (FPR) to produce reactive oxygen species (ROS) that down-regulate NK cell function, we suggested it to be of importance in HSV-2 pathogenesis. We now describe the effects of an overlapping peptide, gG-2p19, derived from the same HSV-2 protein. Also, this peptide activated the ROS-generating NADPH-oxidase, however, only in monocytes and not in neutrophils. Surprisingly, gG-2p19 did not induce a chemotactic response in the affected monocytes despite using a pertussis toxin-sensitive, supposedly G-protein-coupled receptor. The specificity for monocytes suggested that FPR and its homologue FPR like-1 (FPRL1) did not function as receptors for gG-2p19, and this was also experimentally confirmed. Surprisingly, the monocyte-specific FPR homologue FPRL2 was not involved either, and the responsible receptor thus remains unknown so far. However, the receptor shares some basic signaling properties with FPRL1 in that the gG-2p19-induced response was inhibited by PBP10, a peptide that has earlier been shown to selectively inhibit FPRL1-triggered responses. We conclude that secretion and subsequent degradation of the HSV-2 glycoprotein G can generate several peptides that activate phagocytes through different receptors, and with different cellular specificities, to generate ROS with immunomodulatory properties.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by the Swedish Medical Research Council (including a Senior Researcher position for K.E.), the King Gustaf V 80-Year Foundation, the Torsten and Ragnar Söderberg’s foundation, the Göteborg Rheumatism Association, and the Swedish state under the ALF-agreement.
2 L.B. and J.K. have contributed equally to the present work.
3 Current address: Department of Pharmacology, New York Medical College, Valhalla, NY 10595
4 Address correspondence and reprint requests to Dr. Kristina Eriksson, Department of Rheumatology and Inflammation Research, Guldhedsgatan 10A, 413 46 Göteborg, Sweden. E-mail address: kristina.eriksson{at}microbio.gu.se
5 Abbreviations used in this paper: GPCR, G-protein coupled chemoattractant receptors; CL, chemiluminiscence; FPR, formyl peptide receptor; FPRL1, FPR like-1; FPRL2, FPR like-2; KRG, Krebs-Ringer phosphate buffer; N-t-Boc-MLF, N-t-butoxycarbonyl-methionyl-leucyl-phenylalanine; ROS, reactive oxygen species; sgG-2, secreted portion of HSV-2 glycoprotein G.
This article has been cited by other articles:
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  G. R. Van de Walle, K. W. Jarosinski, and N. Osterrieder Alphaherpesviruses and Chemokines: Pas de Deux Not Yet Brought to Perfection J. Virol., July 1, 2008; 82(13): 6090 - 6097. [Full Text] [PDF]
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