Cytoskeletal protein transformation in HIV-1-infected macrophage giant cells

Irena Kadiu, Mary Ricardo-Dukelow, Pawel S Ciborowski, Howard Eliot Gendelman

Research output: Contribution to journalArticle

38 Citations (Scopus)

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 proilie 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 esosomal 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.

Original languageEnglish (US)
Pages (from-to)6404-6415
Number of pages12
JournalJournal of Immunology
Volume178
Issue number10
DOIs
StatePublished - May 15 2007

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Cytoskeletal Proteins
Giant Cells
HIV-1
Profilins
Macrophages
Actins
Proteomics
Viruses
Polymerization
Virion
HIV Infections
Phosphorylation
Cell Membrane
Growth
Proteins

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Cytoskeletal protein transformation in HIV-1-infected macrophage giant cells. / Kadiu, Irena; Ricardo-Dukelow, Mary; Ciborowski, Pawel S; Gendelman, Howard Eliot.

In: Journal of Immunology, Vol. 178, No. 10, 15.05.2007, p. 6404-6415.

Research output: Contribution to journalArticle

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