PMID- 7552476 OWN - NLM STAT- MEDLINE DCOM- 19951024 LR - 20191023 IS - 1077-9450 (Print) IS - 1077-9450 (Linking) VI - 10 IP - 2 DP - 1995 Oct 1 TI - Effects of viral virulence on intrauterine growth in SIV-infected fetal rhesus macaques (Macaca mulatta). PG - 129-38 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. FAU - Tarantal, A F AU - Tarantal AF AD - California Regional Primate Research Center, University of California, Davis 95616-8542, USA. FAU - Marthas, M L AU - Marthas ML FAU - Gargosky, S E AU - Gargosky SE FAU - Otysula, M AU - Otysula M FAU - McChesney, M B AU - McChesney MB FAU - Miller, C J AU - Miller CJ FAU - Hendrickx, A G AU - Hendrickx AG LA - eng GR - RR00169/RR/NCRR NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Acquir Immune Defic Syndr Hum Retrovirol JT - Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association JID - 9501482 RN - 67763-96-6 (Insulin-Like Growth Factor I) RN - EC 3.4.- (Endopeptidases) RN - EC 3.4.99.- (insulin-like growth factor binding protein-3 protease) SB - IM MH - Animals MH - CD4-CD8 Ratio MH - *Embryonic and Fetal Development MH - Endopeptidases/blood MH - Female MH - Fetal Blood/metabolism MH - Fetal Growth Retardation/blood/immunology/*virology MH - Fetal Monitoring MH - Gestational Age MH - Insulin-Like Growth Factor I/metabolism MH - Lymphocytes/virology MH - Macaca mulatta MH - Male MH - Oligohydramnios/blood/immunology/*virology MH - Pregnancy MH - Simian Acquired Immunodeficiency Syndrome/blood/*etiology/immunology MH - Simian Immunodeficiency Virus/isolation & purification/*pathogenicity MH - Virulence EDAT- 1995/10/01 00:00 MHDA- 1995/10/01 00:01 CRDT- 1995/10/01 00:00 PHST- 1995/10/01 00:00 [pubmed] PHST- 1995/10/01 00:01 [medline] PHST- 1995/10/01 00:00 [entrez] AID - 10.1097/00042560-199510020-00004 [doi] PST - ppublish SO - J Acquir Immune Defic Syndr Hum Retrovirol. 1995 Oct 1;10(2):129-38. doi: 10.1097/00042560-199510020-00004.