title: Cytoskeletal protein transformation in HIV-1-infected macrophage giant cells.
abstract: The mechanisms linking HIV-1 replication, macrophage biology, and multinucleated giant cell formation are incompletely understood. With the advent of functional proteomics, the characterization, regulation, and transformation of HIV-1-infected macrophage-secreted proteins can be ascertained. To these ends, we performed proteomic analyses of culture fluids derived from HIV-1 infected monocyte-derived macrophages. Robust reorganization, phosphorylation, and exosomal secretion of the cytoskeletal proteins profilin 1 and actin were observed in conjunction with productive viral replication and giant cell formation. Actin and profilin 1 recruitment to the macrophage plasma membrane paralleled virus-induced cytopathicity, podosome formation, and cellular fusion. Poly-l-proline, an inhibitor of profilin 1-mediated actin polymerization, inhibited cytoskeletal transformations and suppressed, in part, progeny virion production. These data support the idea that actin and profilin 1 rearrangement along with exosomal secretion affect viral replication and cytopathicity. Such events favor the virus over the host cell and provide insights into macrophage defense mechanisms used to contain viral growth and how they may be affected during progressive HIV-1 infection.
authors.affiliation: Laboratory of Neuroregeneration, Department of Pharmacology and Experimental Neuroscience, Center for Neurovirology and Neurodegenerative Disorders, University of Nebraska Medical Center, Omaha 68198, USA.
authors.forename: Irena
authors.initials: I
authors.lastname: Kadiu
authors.forename: Mary
authors.initials: M
authors.lastname: Ricardo-Dukelow
authors.forename: Pawel
authors.initials: P
authors.lastname: Ciborowski
authors.forename: Howard E
authors.initials: HE
authors.lastname: Gendelman
mesh_terms: D000199:Actins / Q000502:physiology; D002459:Cell Fusion; D002478:Cells, Cultured; D003588:Cytopathogenic Effect, Viral; D003598:Cytoskeletal Proteins / Q000378:metabolism* / Q000502:physiology; D015726:Giant Cells / Q000276:immunology / Q000378:metabolism* / Q000821:virology*; D015497:HIV-1 / Q000254:growth & development / Q000276:immunology*; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000821:virology*; D010449:Peptide Mapping; D051304:Profilins / Q000502:physiology; D040081:Protein Array Analysis; D040901:Proteomics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014779:Virus Replication / Q000276:immunology
chemical_list: D000199:Actins; D003598:Cytoskeletal Proteins; D051304:Profilins