Nucleoside reverse transcriptase inhibitors and human immunodeficiency virus proteins cause axonal injury in human dorsal root ganglia cultures

Barry Robinson, Zhenzhong Li, Avindra Nath

Research output: Contribution to journalArticlepeer-review

Abstract

Distal symmetric polyneuropathy (DSP) has emerged as the most common complication of human immunodeficiency virus (HIV) infection, which is associated with neuronal injury in the dorsal root ganglion (DRG). With the advent of highly active antiretroviral therapy, especially nucleoside analogs, patients are living longer. Some of the antiretroviral drugs used to treat HIV infection have been associated with neuropathies. The pathogenesis of these neuropathies remains poorly understood. Utilizing a human fetal DRG model of predominantly nociceptive fibers, the authors investigated the effects of HIV gp120 and Tat1-72, alone or in combination with nucleoside analogs on both morphological and ultra-structural changes in DRG neurons. Nucleoside analogs and HIV proteins both caused a significant decrease in the mean axonal length. However, ddI was the most potent, followed by ddC, d4T, and AZT. Despite the combined exposure to toxic dosages of HIV proteins and nucleoside analogs, there appeared to be a ceiling effect on the amount of axonal retraction, indicating that the proximal and distal axon are differentially regulated. In conclusion, both HIV proteins and nucleoside reverse transcriptase inhibitors (NRTIs) cause axonal damage by inducing mitochondrial injury and rearrangement of microtubules.

Original languageEnglish (US)
Pages (from-to)160-167
Number of pages8
JournalJournal of neurovirology
Volume13
Issue number2
DOIs
StatePublished - Mar 2007

Keywords

  • AIDS
  • Antiretroviral
  • Dorsal root ganglia
  • HIV
  • Neuropathy
  • Nucleoside analogs

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Virology

Fingerprint Dive into the research topics of 'Nucleoside reverse transcriptase inhibitors and human immunodeficiency virus proteins cause axonal injury in human dorsal root ganglia cultures'. Together they form a unique fingerprint.

Cite this