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

Raghava Potula, Navneet Dhillion, Yongjun Sui, Christopher A. Zien, Keiko Funa, David Pinson, Matthew S. Mayo, Dinesh K. Singh, Opendra Narayan, Shilpa J Buch

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

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 SHIVKU2 in which we demonstrated heightened expression of PDGF-B chain mRNA. Nuclear run-off analysis established transctiptional 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.

Original languageEnglish (US)
Pages (from-to)815-824
Number of pages10
JournalAmerican Journal of Pathology
Volume165
Issue number3
DOIs
StatePublished - Jan 1 2004

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Proto-Oncogene Proteins c-sis
Simian Immunodeficiency Virus
Encephalitis
HIV
Platelet-Derived Growth Factor
Macrophages
Macaca
Chemotactic Factors
Virus Replication
Chemokines
Brain
Viruses
Messenger RNA
Proteins
Antisense Oligonucleotides
Infection
Mitogens
Northern Blotting
Protein-Tyrosine Kinases
HIV Infections

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Association of platelet-derived growth factor-B chain with simian human immunodeficiency virus encephalitis. / Potula, Raghava; Dhillion, Navneet; Sui, Yongjun; Zien, Christopher A.; Funa, Keiko; Pinson, David; Mayo, Matthew S.; Singh, Dinesh K.; Narayan, Opendra; Buch, Shilpa J.

In: American Journal of Pathology, Vol. 165, No. 3, 01.01.2004, p. 815-824.

Research output: Contribution to journalArticle

Potula, R, Dhillion, N, Sui, Y, Zien, CA, Funa, K, Pinson, D, Mayo, MS, Singh, DK, Narayan, O & Buch, SJ 2004, 'Association of platelet-derived growth factor-B chain with simian human immunodeficiency virus encephalitis', American Journal of Pathology, vol. 165, no. 3, pp. 815-824. https://doi.org/10.1016/S0002-9440(10)63344-5
Potula, Raghava ; Dhillion, Navneet ; Sui, Yongjun ; Zien, Christopher A. ; Funa, Keiko ; Pinson, David ; Mayo, Matthew S. ; Singh, Dinesh K. ; Narayan, Opendra ; Buch, Shilpa J. / Association of platelet-derived growth factor-B chain with simian human immunodeficiency virus encephalitis. In: American Journal of Pathology. 2004 ; Vol. 165, No. 3. pp. 815-824.
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