Apolipoprotein (apo) E4 enhances HIV-1 cell entry in vitro, and the APOE ε4/ε4 genotype accelerates HIV disease progression

Trevor D. Burt, Brian K. Agan, Vincent C. Marconi, Weijing He, Hemant Kulkarni, Jeffrey E. Mold, Marielle Cavrois, Yadong Huang, Robert W. Mahley, Matthew J. Dolan, Joseph M. McCune, Sunil K. Ahuja

Research output: Contribution to journalArticle

125 Scopus citations

Abstract

Originally recognized for their role in lipoprotein metabolism and cardiovascular disease, apolipoprotein (apo) E isoforms (apoE2, apoE3, and apoE4) have also been implicated to play a key role in several biological processes not directly related to their lipid transport function. For example, apoE4 contributes significantly to neurodegeneration in Alzheimer's disease. However, the role of apoE in infectious diseases is less well defined. Here, by examining a large cohort of HIV+ European and African American subjects, we found that the APOE εA/εA genotype is associated with an accelerated disease course and especially progression to death compared with the APOE ε3/ε3 genotype. However, an association between the εA/εA genotype and HIV-associated dementia (HAD), a neurological condition with clinicopathological features similar to Alzheimer's disease, was not detected. Consistent with the genotype-phenotype relationships observed, compared with recombinant apoE3, apoE4 enhanced HIV fusion/cell entry of both R5 and X4 HIV strains in vitro. These findings establish apoE as a determinant of HIV-AIDS pathogenesis and raise the possibility that current efforts to convert apoE4 to an "apoE3-like" molecule to treat Alzheimer's disease might also have clinical applicability in HIV disease.

Original languageEnglish (US)
Pages (from-to)8718-8723
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number25
DOIs
StatePublished - Jun 24 2008

Keywords

  • ApoE
  • Fusion/cell entry
  • HIV/AIDS
  • Infectious diseases

ASJC Scopus subject areas

  • General

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