title: HIV-1 matrix protein p17 binds to the IL-8 receptor CXCR1 and shows IL-8-like chemokine activity on monocytes through Rho/ROCK activation.
abstract: Exogenous HIV-1 matrix protein p17 was found to deregulate biologic activities of many different immune cells that are directly or indirectly involved in AIDS pathogenesis after binding to unknown cellular receptor(s). In particular, p17 was found to induce a functional program in monocytes related to activation and inflammation. In the present study, we demonstrate that CXCR1 is the receptor molecule responsible for p17 chemokine-like activity on monocytes. After CXCR1 binding, p17 was capable of triggering rapid adhesion and chemotaxis of monocytes through a pathway that involved Rho/ROCK. Moreover, CXCR1-silenced primary monocytes lost responsiveness to p17 chemoattraction, whereas CXCR1-transfected Jurkat cells acquired responsiveness. Surface plasmon resonance studies confirmed the capacity of p17 to bind CXCR1 and showed that the p17/CXCR1 interaction occurred with a low affinity compared with that measured for IL-8, the physiologic CXCR1 ligand. In all of its activities, p17 mimicked IL-8, the natural high-affinity ligand of CXCR1. Recent studies have highlighted the role of IL-8 and CXCR1 in HIV-1 replication and AIDS pathogenesis. Our findings herein call for an exploration of the therapeutic potential of blocking the p17/IL-8/CXCR1 axis in HIV-1 infection.
authors.affiliation: Section of Microbiology, Department of Experimental and Applied Medicine, School of Medicine, University of Brescia, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Giagulli
authors.forename: Anna K
authors.initials: AK
authors.lastname: Magiera
authors.forename: Antonella
authors.initials: A
authors.lastname: Bugatti
authors.forename: Francesca
authors.initials: F
authors.lastname: Caccuri
authors.forename: Stefania
authors.initials: S
authors.lastname: Marsico
authors.forename: Marco
authors.initials: M
authors.lastname: Rusnati
authors.forename: William
authors.initials: W
authors.lastname: Vermi
authors.forename: Simona
authors.initials: S
authors.lastname: Fiorentini
authors.forename: Arnaldo
authors.initials: A
authors.lastname: Caruso
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D015488:HIV Antigens / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D019169:Jurkat Cells; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D037342:Pertussis Toxin / Q000494:pharmacology; D011485:Protein Binding; D034622:RNA Interference; D023062:Receptors, Interleukin-8A / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D054460:rho-Associated Kinases / Q000378:metabolism*
chemical_list: D015488:HIV Antigens; D016209:Interleukin-8; D023062:Receptors, Interleukin-8A; D011994:Recombinant Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; C054858:p17 protein, Human Immunodeficiency Virus Type 1; D037342:Pertussis Toxin; D054460:rho-Associated Kinases