Apolipoprotein E4 Suppresses Neuronal-Specific Gene Expression in Maturing Neuronal Progenitor Cells Exposed to HIV

Rebeca Geffin, Ricardo Martinez, Alicia de las Pozas, Biju Issac, Micheline McCarthy

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The apolipoprotein ε4 gene allele and the apolipoprotein E4 protein (ApoE4) are important host susceptibility factors linked to neurocognitive disorders associated with HIV infection or Alzheimer’s disease. Our previous studies showed differential effects of the two most common human ApoE genotypes, APOE3/3 and APOE3/4, on gene expression by differentiating human neuroepithelial progenitor cells continuously exposed to HIV. To investigate the effects of ApoE3 versus ApoE4 isoforms specifically on maturing neurons, we adapted a human neuronal progenitor cell line, hNP1, with ApoE genotype APOE3/3. Differentiating hNP1 cells were exposed for 16 days to HIV- or mock-infected supernatants and to added recombinant ApoE isoforms rApoE3 or rApoE4 to modulate the ApoE phenotype of the cells. Gene expression was investigated using microarray and functional genomics analyses. Added rApoE3 differentially affected 36 genes. Added rApoE4 differentially affected 85 genes; 41 of which were differentially expressed only in HIV or mock-supernatant treated cells, and 80% of which were downregulated. Genes differentially downregulated only by rApoE4 represented multiple neuronal functions related to neurogenesis. Approximately five times more genes were differentially enriched by rApoE4 versus rApoE3 in the Gene Ontology (GO) cellular process analysis, with 4 orders of magnitude greater significance. Half of the top 10 GO processes affected by rApoE4 treatment were neurogenesis-related. The largest differences in gene expression between the two isoforms were observed within the HIV-exposed cultures, suggesting that HIV exposure magnifies ApoE4’s suppressive effect on neuronal gene expression. This study provides evidence for neuronal-specific responses to ApoE4 that could affect neurogenesis and neuronal survival.

Original languageEnglish (US)
Pages (from-to)462-483
Number of pages22
JournalJournal of NeuroImmune Pharmacology
Volume12
Issue number3
DOIs
StatePublished - Sep 1 2017

Fingerprint

Apolipoprotein E4
Apolipoproteins E
Stem Cells
HIV
Neurogenesis
Gene Expression
Protein Isoforms
Gene Ontology
Genes
Down-Regulation
Genotype
Apolipoprotein E3
Neuroepithelial Cells
Apolipoproteins
Genomics
HIV Infections
Alzheimer Disease
Proteins
Alleles
Phenotype

Keywords

  • Apolipoprotein E
  • Gene expression microarray
  • Human Immunodeficiency Virus
  • Neurogenesis
  • Neuron

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Immunology and Allergy
  • Immunology
  • Pharmacology

Cite this

Apolipoprotein E4 Suppresses Neuronal-Specific Gene Expression in Maturing Neuronal Progenitor Cells Exposed to HIV. / Geffin, Rebeca; Martinez, Ricardo; de las Pozas, Alicia; Issac, Biju; McCarthy, Micheline.

In: Journal of NeuroImmune Pharmacology, Vol. 12, No. 3, 01.09.2017, p. 462-483.

Research output: Contribution to journalArticle

Geffin, Rebeca ; Martinez, Ricardo ; de las Pozas, Alicia ; Issac, Biju ; McCarthy, Micheline. / Apolipoprotein E4 Suppresses Neuronal-Specific Gene Expression in Maturing Neuronal Progenitor Cells Exposed to HIV. In: Journal of NeuroImmune Pharmacology. 2017 ; Vol. 12, No. 3. pp. 462-483.
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