Peripheral nerve-derived HIV-1 is predominantly CCR5-dependent and causes neuronal degeneration and neuroinflammation

Gareth Jones, Yu Zhu, Claudia Silva, Shigeki Tsutsui, Carlos A. Pardo, Oliver T. Keppler, Justin C. McArthur, Christopher Power

Research output: Contribution to journalArticle

Abstract

HIV-related peripheral neuropathy is a major neurological complication of HIV infection, although little is known about its pathogenesis. We amplified HIV-1 C2V3 envelope sequences from peroneal nerves obtained from HIV/AIDS patients. Sequence analysis and infectious recombinant viruses containing peripheral nerve-derived C2V3 sequences indicated a predominance of CCR5-dependent and macrophage-tropic HIV-1, although dual tropic viruses using both CCR5 and CXCR4 were identified. The neuropathogenic effects of recombinant HIV-1 clones were investigated using a novel dorsal root ganglion culture system that was comprised of sensory neurons, macrophages and Schwann cells from transgenic rats expressing human CD4 and CCR5 on monocytoid cells. Despite restricted viral replication, HIV-1 infection caused a reduction in the percentage of neurons with neuritic processes together with significant neurite retraction, which was accompanied by induction of IL-1β and TNF-α expression, depending on the individual virus. Our results suggest that HIV-1 infection of the peripheral nervous system causes axonal degeneration, possibly through the induction of pro-inflammatory cytokines.

Original languageEnglish (US)
Pages (from-to)178-193
Number of pages16
JournalVirology
Volume334
Issue number2
DOIs
StatePublished - Apr 10 2005

Keywords

  • Co-receptor
  • Dorsal root ganglion
  • HIV-1
  • Neuroinflammation
  • Neuropathy
  • Peripheral nerve
  • Tropism

ASJC Scopus subject areas

  • Virology

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