Association of platelet-derived growth factor-B chain with simian human immunodeficiency virus encephalitis.

• Chemokines and cytokines play a critical role in HIV infection, serving both to modulate virus replication and to recruit target cells to the site of infection. Platelet-derived growth factor (PDGF), a mitogen and chemoattractant for a wide variety of cells, is secreted by macrophages. Since macrophages are the target cells for lentiviral infection in the brain and PDGF is a known inducer of macrophage chemoattractant protein-1 (MCP)-1, a potent chemokine closely associated with HIV encephalitis, we investigated the association of PDGF-B chain (PDGF-B) with encephalitis in macaques caused by simian human immunodeficiency virus (SHIV), a chimera of HIV and SIV. Northern blot analysis confirmed elevated expression of PDGF-B chain mRNA in the brains from encephalitic macaques. Validation of these in vivo studies was confirmed in rhesus macrophage cultures infected with SHIV(KU2) in which we demonstrated heightened expression of PDGF-B chain mRNA. Nuclear run-off analysis established transcriptional up-regulation of PDGF-B chain in virus-inoculated macrophage cultures. Reciprocally, addition of exogenous PDGF enhanced virus replication and MCP-1 expression in these cells. Inhibition of virus replication by tyrosine kinase inhibitor, STI-571, and by PDGF-B antisense oligonucleotides confirmed the specificity of the PDGF effect. Relevance of these findings was confirmed by analysis of archival brain tissue from SHIV encephalitic and non-encephalitic macaques for PDGF-B chain expression. PDGF-B chain protein expression was observed in the virus-infected cells in microglial nodules in the brains of SHIV-encephalitic macaques.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

Nyckelord

Animals

Blotting

Northern

Brain

immunology

virology

Cells

Cultured

Chemokine CCL4

DNA

Viral

genetics

Encephalitis

Viral

etiology

metabolism

HIV-1

genetics

pathogenicity

Humans

Macaca mulatta

Macrophage Inflammatory Proteins

metabolism

Macrophages

drug effects

virology

Oligonucleotides

Antisense

pharmacology

Piperazines

pharmacology

Proto-Oncogene Proteins c-sis

antagonists & inhibitors

genetics

metabolism

Pyrimidines

pharmacology

Retroviruses

Simian

pathogenicity

Simian Acquired Immunodeficiency Syndrome

blood

virology

Simian immunodeficiency virus

genetics

pathogenicity

Transcription

Genetic

Up-Regulation

Virus Replication

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)