Inhibition of murine embryonic growth by human immunodeficiency virus envelope protein and its prevention by vasoactive intestinal peptide and activity-dependent neurotrophic factor.
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 viral 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 postimplantation embryonic growth, and the neuroprotective protein, activity-dependent neurotrophic factor, prevent gp120-induced neurotoxicity. Whole embryo culture of gestational 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.
Dibbern
D A
DA
Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
Glazner
G W
GW
Gozes
I
I
Brenneman
D E
DE
Hill
J M
JM
D000818:Animals; D003470:Culture Media; D046508:Culture Techniques; D004247:DNA / Q000378:metabolism; D004622:Embryo, Mammalian / Q000378:metabolism; D005314:Embryonic and Fetal Development; D005317:Fetal Growth Retardation / Q000209:etiology / Q000517:prevention & control; D015699:HIV Envelope Protein gp120 / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009414:Nerve Growth Factors / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009479:Neuropeptides / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009842:Oligopeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
C495402:Adcyap1 protein, mouse; C495403:Adcyap1 protein, rat; D003470:Culture Media; D015699:HIV Envelope Protein gp120; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D018696:Neuroprotective Agents; D009842:Oligopeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011506:Proteins; C410622:activity-dependent neurotrophic factor; D014660:Vasoactive Intestinal Peptide; D004247:DNA