       Document 0627
 DOCN  M9610627
 TI    Effects of viral virulence on intrauterine growth in SIV-infected fetal
       rhesus macaques (Macaca mulatta).
 DT    9601
 AU    Tarantal AF; Marthas ML; Gargosky SE; Otysula M; McChesney MB; Miller
       CJ; Hendrickx AG; California Regional Primate Research Center,
       University of; California, Davis 95616-8542, USA.
 SO    J Acquir Immune Defic Syndr Hum Retrovirol. 1995 Oct 1;10(2):129-38.
       Unique Identifier : AIDSLINE MED/96007274
 AB    Studies with a simian immunodeficiency virus (SIV)-infected fetal monkey
       model were conducted with a focus on fetal growth and viral
       pathogenesis. Twenty-six fetuses were inoculated in utero via ultrasound
       guidance with an uncloned pathogenic strain of SIV or vehicle during the
       second or third trimesters [gestational day (GD) 65, 110, or 130],
       sonographically monitored weekly (biometrics, blood flow), then
       necropsied at incremental time points postinfection. Peripheral blood
       hematologic (complete blood counts, clinical chemistries), immunologic
       (immunophenotyping), and endocrine studies [insulin-like growth factor
       (IGF), IGF-binding proteins (IGFBP)] were conducted. Severe intrauterine
       growth restriction (IUGR), oligohydramnios, and altered lymphocyte
       counts were noted for fetuses infected on GD 65. Less severe effects
       were detected for fetuses inoculated at the later time points, with
       severity dependent upon the length of SIV infection in utero. IGF
       studies indicated significant reductions in IGF-I and elevated
       immunoreactive levels of IGFBP-3 in infected fetuses during the third
       trimester. Parallel studies conducted with four fetuses infected on GD
       65 with a nonpathogenic, molecularly cloned virus (SIVmac1A11) resulted
       in normal fetal growth, with no effects on hematopoiesis or IGF/IGFBP
       levels, and no evidence of clinical disease. Taken together, these
       studies show that (1) infection of fetuses during the early second
       trimester with an uncloned pathogenic strain of SIV results in severe
       IUGR and a disruption in the molar ratio of IGF:IGFBP-3, and (2) outcome
       of fetal SIV infection is determined by the timing of infection and the
       virulence of the viral inoculum.
 DE    Animal  CD4-CD8 Ratio  Female  Fetal Blood/METABOLISM  *Fetal
       Development  Fetal Growth Retardation/BLOOD/IMMUNOLOGY/*VIROLOGY  Fetal
       Monitoring  Gestational Age  Insulin-Like Growth Factor I/METABOLISM
       Lymphocytes/VIROLOGY  Macaca mulatta  Male
       Oligohydramnios/BLOOD/IMMUNOLOGY/*VIROLOGY  Peptide
       Peptidohydrolases/BLOOD  Pregnancy  Simian Acquired Immunodeficiency
       Syndrome/BLOOD/*ETIOLOGY/  IMMUNOLOGY  Support, U.S. Gov't, P.H.S.
       SIV/ISOLATION & PURIF/*PATHOGENICITY  Virulence  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

