Insulin-like growth factor 2 receptor is an IFNγ-inducible microglial protein that facilitates intracellular HIV replication

Implications for HIV-induced neurocognitive disorders

Hyeon Sook Suh, Melissa Cosenza-Nashat, Namjong Choi, Meng Liang Zhao, Jiu Feng Li, Jeffrey W. Pollard, Randy L. Jirtle, Harris Goldstein, Sunhee C. Lee

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Insulin-like growth factor 2 receptor (IGF2R), also known as cation-independent mannose 6-phosphate (M6P) receptor, is a transmembrane glycoprotein localized in the trans-Golgi region and is involved in targeting both M6P-bearing enzymes and IGF2 to the lysosomal compartment. During development, IGF2R plays a crucial role in removing excess growth factors from both tissue and blood. Due to the perinatal lethality of the global Igf2r knockout, the function of IGF2R in adults, particularly in the CNS, is not known. We made a novel observation that IGF2R is highly expressed in microglial nodules in human brains with HIV encephalitis. In vitro, microglial IGF2R expression was uniquely enhanced by IFNγ among the several cytokines and TLR ligands examined. Furthermore, in several in vitro models of HIV infection, including human and murine microglia, macrophages, and nonmacrophage cells, IGF2R is repeatedly shown to be a positive regulator of HIV infection. IGF2R RNAi also down-regulated the production of the IP-10 chemokine in HIV-infected human microglia. Injection of VSVg env HIV into mouse brain induced HIV p24 expression in neurons, the only cell type normally expressing IGF2R in the adult brain. Our results demonstrate a novel role for IGF2R as an inducible microglial protein involved in regulation of HIV and chemokine expression. Mice with the Csf1r- driven Igf2r knockout should be useful for the investigation of macrophage-specific IGF2R function.

Original languageEnglish (US)
Pages (from-to)2446-2458
Number of pages13
JournalAmerican Journal of Pathology
Volume177
Issue number5
DOIs
StatePublished - Nov 2010

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Somatomedin Receptors
HIV
Proteins
Microglia
Chemokines
HIV Infections
Brain
HIV Core Protein p24
Macrophages
Neurocognitive Disorders
IGF Type 2 Receptor
trans-Golgi Network
Encephalitis
RNA Interference
Cations
Intercellular Signaling Peptides and Proteins
Glycoproteins
Observation
Cytokines
Ligands

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Insulin-like growth factor 2 receptor is an IFNγ-inducible microglial protein that facilitates intracellular HIV replication : Implications for HIV-induced neurocognitive disorders. / Suh, Hyeon Sook; Cosenza-Nashat, Melissa; Choi, Namjong; Zhao, Meng Liang; Li, Jiu Feng; Pollard, Jeffrey W.; Jirtle, Randy L.; Goldstein, Harris; Lee, Sunhee C.

In: American Journal of Pathology, Vol. 177, No. 5, 11.2010, p. 2446-2458.

Research output: Contribution to journalArticle

Suh, Hyeon Sook ; Cosenza-Nashat, Melissa ; Choi, Namjong ; Zhao, Meng Liang ; Li, Jiu Feng ; Pollard, Jeffrey W. ; Jirtle, Randy L. ; Goldstein, Harris ; Lee, Sunhee C. / Insulin-like growth factor 2 receptor is an IFNγ-inducible microglial protein that facilitates intracellular HIV replication : Implications for HIV-induced neurocognitive disorders. In: American Journal of Pathology. 2010 ; Vol. 177, No. 5. pp. 2446-2458.
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