An oral form of methylglyoxal-bis-guanylhydrazone reduces monocyte activation and traffic to the dorsal root ganglia in a primate model of HIV-peripheral neuropathy

J Neurovirol. 2017 Aug;23(4):568-576. doi: 10.1007/s13365-017-0529-9. Epub 2017 May 1.


Peripheral neuropathy (PN) is a major comorbidity of HIV infection that is caused in part by chronic immune activation. HIV-PN is associated with infiltration of monocytes/macrophages to the dorsal root ganglia (DRG) causing neuronal loss and formation of Nageotte nodules. Here, we used an oral form of methylglyoxal-bis-guanylhydrazone (MGBG), a polyamine biosynthesis inhibitor, to specifically reduce activation of myeloid cells. MGBG is selectively taken up by monocyte/macrophages in vitro and inhibits HIV p24 expression and DNA viral integration in macrophages. Here, MGBG was administered to nine SIV-infected, CD8-depleted rhesus macaques at 21 days post-infection (dpi). An additional nine SIV-infected, CD8-depleted rhesus macaques were used as untreated controls. Cell traffic to tissues was measured by in vivo BrdU pulse labeling. MGBG treatment significantly diminished DRG histopathology and reduced the number of CD68+ and CD163+ macrophages in DRG tissue. The number of recently trafficked BrdU+ cells in the DRG was significantly reduced with MGBG treatment. Despite diminished DRG pathology, intraepidermal nerve fiber density (IENFD) did not recover after treatment with MGBG. These data suggest that MGBG alleviated DRG pathology and inflammation.

Keywords: Dorsal root ganglia; HIV; Monocyte; Peripheral neuropathy; Polyamine biosynthesis inhibitor; Rhesus.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Oral
  • Animals
  • CD8-Positive T-Lymphocytes / virology
  • Cell Movement / drug effects
  • DNA, Viral / genetics
  • Enzyme Inhibitors / pharmacology*
  • Ganglia, Spinal / drug effects*
  • Ganglia, Spinal / immunology
  • Ganglia, Spinal / pathology
  • Ganglia, Spinal / virology
  • HIV Core Protein p24 / genetics
  • Lymphocyte Depletion
  • Macaca mulatta
  • Macrophages / drug effects
  • Macrophages / immunology
  • Macrophages / pathology
  • Macrophages / virology
  • Male
  • Mitoguazone / pharmacology*
  • Monocytes / drug effects*
  • Monocytes / immunology
  • Monocytes / pathology
  • Monocytes / virology
  • Nerve Fibers / drug effects
  • Nerve Fibers / immunology
  • Nerve Fibers / pathology
  • Nerve Fibers / virology
  • Peripheral Nervous System Diseases / drug therapy*
  • Peripheral Nervous System Diseases / immunology
  • Peripheral Nervous System Diseases / pathology
  • Peripheral Nervous System Diseases / virology
  • Polyamines / antagonists & inhibitors
  • Polyamines / metabolism
  • Simian Acquired Immunodeficiency Syndrome / drug therapy*
  • Simian Acquired Immunodeficiency Syndrome / immunology
  • Simian Acquired Immunodeficiency Syndrome / pathology
  • Simian Acquired Immunodeficiency Syndrome / virology
  • Simian Immunodeficiency Virus / drug effects
  • Simian Immunodeficiency Virus / genetics
  • Simian Immunodeficiency Virus / growth & development


  • DNA, Viral
  • Enzyme Inhibitors
  • HIV Core Protein p24
  • Polyamines
  • Mitoguazone