Anti-HCMV and KSHV effect of a trapping ligand antagonist for herpesvirus-encoded GPCR.
We have found and synthesized a trapping ligand peptide H22-LP (the conservative sequence is NAHCALL) from a random phage library according to the broad-spectrum trapping receptor H22, which derived from the residue 14-35 near the N-terminal region of receptor US28 on HCMV. In this study, we will evaluate its potential as an efficient antagonist of US28 and the anti-virus activity, acting as a broad spectrum chemokine receptors antagonist. Stable expression of US28 and ORF74 in NIH/3T3 cells were successfully constructed in vitro. Flow cytomety was used to determine the concentration of Ca2+ induced by H22-LP, and the binding of H22-LP and US28 was confirmed by enzyme-linked immunosorbent assay (ELISA). Antivirus activity of H22-LP on HCMV and KSHV was evaluated by anti-virus experiments. Our data suggest that H22-LP is an effectual antagonist of receptor US28 of HCMV and ORF74 of KSHV in the transfection assay, and it has potential to inhibit infection of HCMV and KSHV. These results provide support for the development of anti-virus strategies based on targeted inhibiting the infection of herpesvirus.
Institute of Genomic Medicine, College of Pharmacy, Jinan University, Guangzhou 510632, China.
Hong-Ai
HA
Liu
Han-Xiao
HX
Sun
Xue-Mei
XM
Mo
Shi-Yu
SY
Li
Xiu-Ying
XY
Li
Guang
G
Zhang
Li
L
Lu
D000818:Animals; D003587:Cytomegalovirus / Q000187:drug effects / Q000235:genetics* / Q000472:pathogenicity; D019288:Herpesvirus 8, Human / Q000187:drug effects / Q000235:genetics* / Q000472:pathogenicity; D006801:Humans; D008024:Ligands; D051379:Mice; D041681:NIH 3T3 Cells; D010455:Peptides / Q000008:administration & dosage* / Q000235:genetics*; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors / Q000235:genetics*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D014764:Viral Proteins / Q000037:antagonists & inhibitors / Q000235:genetics*
D008024:Ligands; C105181:ORF74 protein, Human herpesvirus 8; D010455:Peptides; D019707:Receptors, Chemokine; D043562:Receptors, G-Protein-Coupled; C411191:US28 receptor, Cytomegalovirus; D014764:Viral Proteins