HIV-1 and HIV-2 differentially mature plasmacytoid dendritic cells into IFN-Producing cells or APCs

Caroline M. Royle, David R. Graham, Simone Sharma, Dietmar Fuchs, Adriano Boasso

Research output: Contribution to journalArticlepeer-review

Abstract

HIV-1 causes a progressive impairment of immune function. HIV-2 is a naturally attenuated form of HIV, and HIV-2 patients display a slow-progressing disease. The leading hypothesis for the difference in disease phenotype between HIV-1 and HIV-2 is that more efficient T cell-mediated immunity allows for immune-mediated control of HIV-2 infection, similar to that observed in the minority of HIV-1-infected long-term nonprogressors. Understanding how HIV-1 and HIV-2 differentially influence the immune function may highlight critical mechanisms determining disease outcome. We investigated the effects of exposing primary human peripheral blood cells to HIV-1 or HIV-2 in vitro. HIV-2 induced a gene expression profile distinct from HIV-1, characterized by reduced type I IFN, despite similar upregulation of IFN-stimulated genes and viral restriction factors. HIV-2 favored plasmacytoid dendritic cell (pDC) differentiation into cells with an APC phenotype rather than IFN-a-producing cells. HIV-2, but not HIV-1, inhibited IFN-α production in response to CpG-A. The balance between pDC maturation into IFN-α-producing cells or development of an APC phenotype differentiates the early response against HIV-1 and HIV-2. We propose that divergent paths of pDC differentiation driven by HIV-1 and HIV-2 cause the observed differences in pathogenicity between the two viruses.

Original languageEnglish (US)
Pages (from-to)3538-3548
Number of pages11
JournalJournal of Immunology
Volume193
Issue number7
DOIs
StatePublished - Oct 1 2014

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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