A monocyte-specific peptide from herpes simplex virus type 2 glycoprotein G activates the NADPH-oxidase but not chemotaxis through a G-protein-coupled receptor distinct from the members of the formyl peptide receptor family.
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.
Bellner
Lars
L
Department of Rheumatology and Inflammation Research, Göteborg University, Göteborg, Sweden.
Karlsson
Jennie
J
Fu
Huamei
H
Boulay
François
F
Dahlgren
Claes
C
Eriksson
Kristina
K
Karlsson
Anna
A
D000595:Amino Acid Sequence; D002633:Chemotaxis / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D008024:Ligands; D008969:Molecular Sequence Data; D009000:Monocytes / Q000187:drug effects* / Q000201:enzymology; D019255:NADPH Oxidases / Q000378:metabolism*; D020239:Receptor Cross-Talk; D044042:Receptors, Formyl Peptide / Q000145:classification* / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D012680:Sensitivity and Specificity; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000494:pharmacology*
D008024:Ligands; D044042:Receptors, Formyl Peptide; D043562:Receptors, G-Protein-Coupled; D014759:Viral Envelope Proteins; C045464:glycoprotein G, herpes simplex virus type 2; D019255:NADPH Oxidases