Inhibition of murine embryonic growth by human immunodeficiency virus envelope protein and its prevention by vasoactive intestinal peptide and activity-dependent neurotrophic factor

Donald A. Dibbern, Gordon W. Glazner, Illana Gozes, Douglas E. Brenneman, Joanna M. Hill*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Intrauterine growth retardation and neurodevelopmental handicaps are common among infants born to HIV-positive mothers and may be due to the actions of virions and/or maternally derived viral products. The vital envelope protein, gp120, is toxic to neurons, induces neuronal dystrophy, and retards behavioral development in neonatal rats. Vasoactive intestinal peptide, a neuropeptide regulator of early post-implantation embryonic growth, and the neuroprotective protein, activity-dependent neurotrophic factor, prevent gp120-induced neurotoxicity. Whole embryo culture of gesrational day 9.5 mouse embryos was used to assess the effect of gp120 on growth. Embryos treated with gp120 exhibited a dose-dependent inhibition of growth. gp120-treated embryos (10-8 M) grew 1.2 somites in the 6-h incubation period, compared with 3.9 somites by control embryos. Embryos treated with gp120 were significantly smaller in cross-sectional area and had significantly less DNA and protein than controls. Growth inhibition induced by gp120 was prevented by cotreatment with vasoactive intestinal peptide or activity-dependent neurotrophic factor, gp120 may play a role in the growth retardation and developmental delays experienced by infants born to HIV- positive mothers. Vasoactive intestinal peptide and related factors may provide a therapeutic strategy in preventing developmental deficits.

Original languageEnglish
Pages (from-to)2837-2841
Number of pages5
JournalJournal of Clinical Investigation
Volume99
Issue number12
DOIs
StatePublished - 15 Jun 1997

Keywords

  • Activity-dependent neurotrophic factor
  • Embryo
  • Growth retardation
  • Human immunodeficiency virus gp120
  • Vasoactive intestinal peptide

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