Platelet factor 4 (CXCL4) facilitates human macrophage infection with HIV-1 and potentiates virus replication.
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-1alpha; 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.
Department of Immunology and Cell Biology, Research Center Borstel, Germany.
Franziska
F
Schwartzkopff
Tobias A
TA
Grimm
Carla S R
CS
Lankford
Karen
K
Fields
Jiun
J
Wang
Ernst
E
Brandt
Kathleen A
KA
Clouse
D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D054405:Chemokine CCL3 / Q000378:metabolism; D015658:HIV Infections / Q000097:blood / Q000276:immunology*; D015497:HIV-1 / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D018448:Models, Immunological; D010978:Platelet Factor 4 / Q000276:immunology / Q000378:metabolism*; D019713:Receptors, CCR5 / Q000378:metabolism; D014774:Virulence; D053586:Virus Internalization; D014779:Virus Replication
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D019713:Receptors, CCR5; D010978:Platelet Factor 4; D016173:Macrophage Colony-Stimulating Factor