HIV infection of children results in a higher incidence of neurologic disease than is seen in adults To explore the pathogenesis of neonatal infection of the CNS, we examined 20 rhesus macaque neonates inoculated intravenously with SIV within 24 hours of birth The viral inocula included the pathogenic molecular clone SIVmac239 (n = 13), the macrophage-competent derivative SIVmac239/316 (n = 2), the minimally pathogenic SIVmac239 nef (n = 2) and uncloned SIVmac251 (n = 3) Infected neonates were sacrificed at intervals over the first 50 days (n = 16) or allowed to progress to terminal disease (n =4) Viral DNA was detected in the brain by nested PCR for gag by day 3 and viral RNA was detected by radiolabeled in situ hybridization (ISH) by day 7 Histologic changes in the brain were limited to mild perivascular infiltrates of mononuclear cells and focal mineralization of vessels in the basal ganglia Cells positive for SIV by ISH were occasionally associated w ith vessels and found most often in the cortical gray matter and basal ganglia In addition, many infected cells were scattered throughout the parenchyma without any associated histologic lesions In total, 8/13 SIVmac239-, 1/2 SIVmac239/316-, 2/3 SIVmac251- and 0/2 SIVmac239 nef-infected neonates had virus detected in the CNS by ISH However, the number of infected cells was low and virus was not detectable by immunohistochemistry or nonradiolabeled ISH In contrast to the limited infection of the CNS these same animals (excluding those inoculated with SIVmac239 nef) had high viral loads in peripheral blood and abundant virus in lymphoid organs Furthermore, the number of infected cells in the CNS was much less than that observed previously in adult macaques inoculated with the same dose and stock of virus Thus, while neuroinvasion by these stocks of SIV in neonates is comparable to that observed in older animals, the number of infected cells and severity of lesions was limited T his may be related to the abundance of CD4+ T cells in the periphery of neonates and a relative paucity of infection of monocyte/macrophages evident by combined in situ hybridization/immunohistochemistry

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000168-38
Application #
6116538
Study Section
Project Start
1999-05-01
Project End
2000-04-30
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
38
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Harvard University
Department
Type
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115
Shang, L; Smith, A J; Reilly, C S et al. (2018) Vaccine-modified NF-kB and GR signaling in cervicovaginal epithelium correlates with protection. Mucosal Immunol 11:512-522
Sonntag, Kai-Christian; Woo, Tsung-Ung W (2018) Laser microdissection and gene expression profiling in the human postmortem brain. Handb Clin Neurol 150:263-272
Almodovar, Sharilyn; Swanson, Jessica; Giavedoni, Luis D et al. (2018) Lung Vascular Remodeling, Cardiac Hypertrophy, and Inflammatory Cytokines in SHIVnef-Infected Macaques. Viral Immunol 31:206-222
Duke, Angela N; Meng, Zhiqiang; Platt, Donna M et al. (2018) Evidence That Sedative Effects of Benzodiazepines Involve Unexpected GABAA Receptor Subtypes: Quantitative Observation Studies in Rhesus Monkeys. J Pharmacol Exp Ther 366:145-157
Kamberov, Yana G; Guhan, Samantha M; DeMarchis, Alessandra et al. (2018) Comparative evidence for the independent evolution of hair and sweat gland traits in primates. J Hum Evol 125:99-105
Seth, Nitin; Simmons, Heather A; Masood, Farah et al. (2018) Model of Traumatic Spinal Cord Injury for Evaluating Pharmacologic Treatments in Cynomolgus Macaques (Macaca fasicularis). Comp Med 68:63-73
Mauney, Sarah A; Woo, Tsung-Ung W; Sonntag, Kai C (2018) Cell Type-Specific Laser Capture Microdissection for Gene Expression Profiling in the Human Brain. Methods Mol Biol 1723:203-221
Termini, James M; Church, Elizabeth S; Silver, Zachary A et al. (2017) Human Immunodeficiency Virus and Simian Immunodeficiency Virus Maintain High Levels of Infectivity in the Complete Absence of Mucin-Type O-Glycosylation. J Virol 91:
Ma, Qi; Ruan, Hongyu; Peng, Lisheng et al. (2017) Proteasome-independent polyubiquitin linkage regulates synapse scaffolding, efficacy, and plasticity. Proc Natl Acad Sci U S A 114:E8760-E8769
Shang, L; Duan, L; Perkey, K E et al. (2017) Epithelium-innate immune cell axis in mucosal responses to SIV. Mucosal Immunol 10:508-519

Showing the most recent 10 out of 365 publications