Platelet factor 4 (CXCL4) facilitates human macrophage infection with HIV-1 and potentiates virus replication

Abstract

Platelet factor 4 (CXCL4), a member of the CXC chemokine subfamily released in high amounts by activated platelets, has been identified as a monocyte survival factor that induces monocyte differentiation into macrophages. Although CXCL4 has been shown to have biological effects unique to chemokines, nothing is known about the role of CXCL4-derived human macrophages or CXCL4 in human immunodeficiency virus (HIV) disease. In this study, CXCL4-derived macrophages are compared with macrophage-colony stimulating factor (M-CSF)-derived macrophages for their ability to support HIV-1 replication. We show that CXCL4-derived macrophages can be infected with macrophage-tropic HIV-1 that uses either CC-chemokine receptor 5 (CCR5) or CXC-chemokine receptor 4 (CXCR4) as a co-receptor for viral entry. We also find that M-CSF and the chemokines, monocyte chemoattractant protein 1 (MCP-1; CCL2) and macrophage-inflammatory-protein-1-alpha (MIP-1α; CCL3) are produced upon R5- and X4-tropic HIV-1 replication in both M-CSF- and CXCL4-derived human macrophages. In addition, CXCL4 added to M-CSF-derived macrophages after virus adsorption and maintained throughout the infection enhances HIV-1 replication. We thus propose a novel role for CXCL4 in HIV disease.

Keywords

CXCL4 cytokines HIV-1 macrophages M-CSF

References

Files JC , Malpass TW , Yee EK , Ritchie JL , Harker LA Studies of human platelet alpha-granule release in vivo. Blood 1981; 58: 607-618.

Kameyoshi Y. , Schroder JM , Christophers E. , Yamamoto S. Identification of the cytokine RANTES released from platelets as an eosinophil chemotactic factor. Int Arch Allergy Immunol 1994; 104 (Suppl 1): 49-51.

Moore S. , Pepper DS , Cash JD Platelet antiheparin activity. The isolation and characterisation of platelet factor 4 released from thrombin-aggregated washed human platelets and its dissociation into subunits and the isolation of membrane-bound antiheparin activity. Biochim Biophys Acta 1975; 379: 370-384.

Brandt E. , Ludwig A. , Petersen F. , Flad HD Platelet-derived CXC chemokines: old players in new games. Immunol Rev 2000; 177: 204-216.

Zucker MB , Katz IR Platelet factor 4: production, structure, and physiologic and immunologic action. Proc Soc Exp Biol Med 1991; 198: 693-702.

Pervushina O. , Scheuerer B. , Reiling N. et al. Platelet factor 4/ CXCL4 induces phagocytosis and the generation of reactive oxygen metabolites in mononuclear phagocytes independently of Gi protein activation or intracellular calcium transients . J Immunol 2004; 173: 2060-2067.

Petersen F. , Ludwig A. , Flad HD , Brandt E. TNF-alpha renders human neutrophils responsive to platelet factor 4. Comparison of PF-4 and IL-8 reveals different activity profiles of the two chemokines . J Immunol 1996; 156: 1954-1962.

Watson JB , Getzler SB , Mosher DF Platelet factor 4 modulates the mitogenic activity of basic fibroblast growth factor. J Clin Invest 1994; 94: 261-268.

Lasagni L. , Francalanci M. , Annunziato F. et al. An alternatively spliced variant of CXCR3 mediates the inhibition of endothelial cell growth induced by IP-10, Mig, and I-TAC, and acts as functional receptor for platelet factor 4. J Exp Med 2003; 197: 1537-1549.

10.

Fleischer J. , Grage-Griebenow E. , Kasper B. et al. Platelet factor 4 inhibits proliferation and cytokine release of activated human T cells. J Immunol 2002; 169: 770-777.

11.

Kedzierska K. , Crowe SM Cytokines and HIV-1: interactions and clinical implications. Antivir Chem Chemother 2001; 12: 133-150.

12.

Scheuerer B. , Ernst M. , Durrbaum-Landmann I. et al. The CXC-chemokine platelet factor 4 promotes monocyte survival and induces monocyte differentiation into macrophages. Blood 2000; 95: 1158-1166.

13.

Han ZC , Lu M. , Li J. et al. Platelet factor 4 and other CXC chemokines support the survival of normal hematopoietic cells and reduce the chemosensitivity of cells to cytotoxic agents. Blood 1997; 89: 2328-2335.

14.

Han ZC , Bellucci S. , Walz A. , Baggiolini M. , Caen JP Negative regulation of human megakaryocytopoiesis by human platelet factor 4 (PF4) and connective tissue-activating peptide (CTAP-III). Int J Cell Cloning 1990; 8: 253-259.

15.

Igarashi T. , Brown CR , Endo Y. et al. Macrophage are the principal reservoir and sustain high virus loads in rhesus macaques after the depletion of CD4+ T cells by a highly pathogenic simian immunodeficiency virus/HIV type 1 chimera (SHIV): implications for HIV-1 infections of humans. Proc Natl Acad Sci USA 2001; 98: 658-663.

16.

Orenstein JM , Fox C. , Wahl SM Macrophages as a source of HIV during opportunistic infections. Science 1997; 276: 1857-1861.

17.

Bjorndal A. , Deng H. , Jansson M. et al. Coreceptor usage of primary human immunodeficiency virus type 1 isolates varies according to biological phenotype. J Virol 1997; 71: 7478-7487.

18.

Moore JP , Kitchen SG , Pugach P. , Zack JA The CCR5 and CXCR4 coreceptors-central to understanding the transmission and pathogenesis of human immunodeficiency virus type 1 infection. AIDS Res Hum Retroviruses 2004; 20: 111-126.

19.

van’t Wout AB , Kootstra NA , Mulder-Kampinga GA et al. Macrophage-tropic variants initiate human immunodeficiency virus type 1 infection after sexual, parenteral, and vertical transmission. J Clin Invest 1994; 94: 2060-2067.

20.

Schuitemaker H. , Koot M. , Kootstra NA et al. Biological phenotype of human immunodeficiency virus type 1 clones at different stages of infection: progression of disease is associated with a shift from monocytotropic to T-cell-tropic virus population . J Virol 1992; 66: 1354-1360.

21.

Singh A. , Collman RG Heterogeneous spectrum of coreceptor usage among variants within a dualtropic human immunodeficiency virus type 1 primary-isolate quasispecies. J Virol 2000; 74: 10229-10235.

22.

Regoes RR , Bonhoeffer S. The HIV coreceptor switch: a population dynamical perspective. Trends Microbiol 2005; 13: 269-277.

23.

Goodenow MM , Collman RG HIV-1 coreceptor preference is distinct from target cell tropism: a dual-parameter nomenclature to define viral phenotypes . J Leukoc Biol 2006; 80: 965-972.

24.

Kedzierska K. , Crowe SM The role of monocytes and macrophages in the pathogenesis of HIV-1 infection. Curr Med Chem 2002; 9: 1893-1903.

25.

Kedzierska K. , Crowe SM , Turville S. , Cunningham AL The influence of cytokines, chemokines and their receptors on HIV-1 replication in monocytes and macrophages. Rev Med Virol 2003; 13: 39-56.

26.

Gruber MF , Weih KA , Boone EJ , Smith PD , Clouse KA Endogenous macrophage CSF production is associated with viral replication in HIV-1-infected human monocyte-derived macrophages. J Immunol 1995; 154: 5528-5535.

27.

Wang J. , Roderiquez G. , Oravecz T. , Norcross MA Cytokine regulation of human immunodeficiency virus type 1 entry and replication in human monocytes/macrophages through modulation of CCR5 expression. J Virol 1998; 72: 7642-7647.

28.

Bergamini A. , Perno CF , Dini L. et al. Macrophage colony-stimulating factor enhances the susceptibility of macrophages to infection by human immunodeficiency virus and reduces the activity of compounds that inhibit virus binding. Blood 1994; 84: 3405-3412.

29.

Muthumani K. , Kudchodkar S. , Papasavvas E. , Montaner LJ , Weiner DB , Ayyavoo V. HIV-1 Vpr regulates expression of beta chemokines in human primary lymphocytes and macrophages. J Leukoc Biol 2000; 68: 366-372.

30.

Mengozzi M. , De Filippi C. , Transidico P. et al. Human immunodeficiency virus replication induces monocyte chemotactic protein-1 in human macrophages and U937 promonocytic cells. Blood 1999; 93: 1851-1857.

31.

Choe W. , Volsky DJ , Potash MJ Activation of NF-kappaB by R5 and X4 human immunodeficiency virus type 1 induces macrophage inflammatory protein 1 alpha and tumor necrosis factor alpha in macrophages. J Virol 2002; 76: 5274-5277.

32.

Struyf S. , Burdick MD , Proost P. , Van Damme J. , Strieter RM Platelets release CXCL4 L1, a nonallelic variant of the chemokine platelet factor-4/CXCL4 and potent inhibitor of angiogenesis. Circ Res 2004; 95: 855-857.

33.

Loussert-Ajaka I. , Chaix ML , Korber B. et al. Variability of human immunodeficiency virus type 1 group O strains isolated from Cameroonian patients living in France. J Virol 1995; 69: 5640-5649.

34.

Fricke I. , Mitchell D. , Petersen F. , Bohle A. , Bulfone-Paus S. , Brandau S. Platelet factor 4 in conjunction with IL-4 directs differentiation of human monocytes into specialized antigen-presenting cells. FASEB J 2004; 18: 1588-1590.

35.

Kutza J. , Crim L. , Feldman S. et al. Macrophage colony-stimulating factor antagonists inhibit replication of HIV-1 in human macrophages. J Immunol 2000 ; 164: 4955-4960.

36.

Berger EA , Doms RW , Fenyo EM et al. A new classification for HIV-1. Nature 1998; 391: 240.

37.

Lee B. , Sharron M. , Montaner LJ , Weissman D. , Doms RW Quantification of CD4, CCR5, and CXCR4 levels on lymphocyte subsets, dendritic cells, and differentially conditioned monocyte-derived macrophages. Proc Natl Acad Sci USA 1999; 96: 5215-5220.

38.

Scarlatti G. , Tresoldi E. , Bjorndal A. et al. In vivo evolution of HIV-1 co-receptor usage and sensitivity to chemokine-mediated suppression. Nat Med 1997 ; 3: 1259-1265.

39.

Kozak SL , Platt EJ , Madani N. , Ferro Jr FE , Peden K. , Kabat D. CD4, CXCR-4, and CCR-5 dependencies for infections by primary patient and laboratory-adapted isolates of human immunodeficiency virus type 1. J Virol 1997; 71: 873-882.

40.

Platt EJ , Wehrly K. , Kuhmann SE , Chesebro B. , Kabat D. Effects of CCR5 and CD4 cell surface concentrations on infections by macrophagetropic isolates of human immunodeficiency virus type 1. J Virol 1998; 72: 2855-2864.

41.

Dimitrov DS , Norwood D. , Stantchev TS , Feng Y. , Xiao X. , Broder CC A mechanism of resistance to HIV-1 entry: inefficient interactions of CXCR4 with CD4 and gp120 in macrophages. Virology 1999; 259: 1-6.

42.

Lee S. , Lapham CK , Chen H. et al. Coreceptor competition for association with CD4 may change the susceptibility of human cells to infection with T-tropic and macrophagetropic isolates of human immunodeficiency virus type 1. J Virol 2000; 74: 5016-5023.

43.

Chang J. , Li S. , Naif H. , Cunningham AL The magnitude of HIV replication in monocytes and macrophages is influenced by environmental conditions, viral strain, and host cells. J Leukoc Biol 1994; 56: 230-235.

44.

Chang J. , Naif HM , Li S. , Sullivan JS , Randle CM , Cunningham AL Twin studies demonstrate a host cell genetic effect on productive human immunodeficiency virus infection of human monocytes and macrophages in vitro. J Virol 1996; 70: 7792-7803.

45.

Kutza J. , Fields K. , Grimm TA , Clouse KA Inhibition of HIV replication and macrophage colony-stimulating factor production in human macrophages by antiretroviral agents. AIDS Res Hum Retroviruses 2002; 18: 619-625.

46.

Lane BR , Lore K. , Bock PJ et al. Interleukin-8 stimulates human immunodeficiency virus type 1 replication and is a potential new target for antiretroviral therapy. J Virol 2001; 75: 8195-8202.

47.

Lane BR , Strieter RM , Coffey MJ , Markovitz DM Human immunodeficiency virus type 1 (HIV-1)-induced GRO-alpha production stimulates HIV-1 replication in macrophages and T lymphocytes. J Virol 2001; 75: 5812-5822.

48.

Fantuzzi L. , Spadaro F. , Vallanti G. et al. Endogenous CCL2 (monocyte chemotactic protein-1) modulates human immunodeficiency virus type-1 replication and affects cytoskeleton organization in human monocyte-derived macrophages. Blood 2003; 102: 2334-2337.

49.

Lane DA , Denton J. , Flynn AM , Thunberg L. , Lindahl U. Anticoagulant activities of heparin oligosaccharides and their neutralization by platelet factor 4. Biochem J 1984; 218: 725-732.

50.

Dumenco LL , Everson B. , Culp LA , Ratnoff OD Inhibition of the activation of Hageman factor (factor XII) by platelet factor 4. J Lab Clin Med 1988; 112: 394-400.

51.

O’Brien JR , Etherington MD , Pashley M. Intra-platelet platelet factor 4 (IP.PF4) and the heparin-mobilisable pool of PF4 in health and atherosclerosis. Thromb Haemost 1984; 51: 354-357.

52.

Maione TE , Gray GS , Petro J. et al. Inhibition of angiogenesis by recombinant human platelet factor-4 and related peptides. Science 1990; 247: 77-79.

53.

Tarhan G. , Gumuslu F. , Yilmaz N. , Saka D. , Ceyhan I. , Cesur S. Serum adenosine deaminase enzyme and plasma platelet factor 4 activities in active pulmonary tuberculosis, HIVseropositive subjects and cancer patients . J Infect 2006; 52: 264-268.