Unique susceptibility of the fetal thymus to feline immunodeficiency virusinfection: An animal model for HIV infection in utero

Citation
Cm. Johnson et al., Unique susceptibility of the fetal thymus to feline immunodeficiency virusinfection: An animal model for HIV infection in utero, AM J REPROD, 45(5), 2001, pp. 273-288
Citations number
92
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Immunology
Journal title
AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY
ISSN journal
1046-7408 → ACNP
Volume
45
Issue
5
Year of publication
2001
Pages
273 - 288
Database
ISI
SICI code
1046-7408(200105)45:5<273:USOTFT>2.0.ZU;2-Q
Abstract
PROBLEM: Human infants infected in utero with HIV develop thymus insufficie ncy and progress to AIDS sooner than infants infected peripartum. However, dir;ect analysis of the thymus is difficult due to limited tissue access an d variable timing of vertical transmission. METHOD OF STUDY: Fetal and neonatal cats were inoculated with feline immuno deficiency virus (FIV) at an equivalent infectious dose. The thymus, blood, and lymph nodes were harvested and compared at 23 and 46 days post-inocula tion (p.i.) and also compared to sham-inoculated, age-matched controls. Lym phocyte phenotypes were analyzed by flow cytometry and virus burden was qua ntified in histologic sections and by virus isolation from plasma. RESULTS: Fetal cats inoculated with FIV had acute thymus atrophy at birth, which coincided with peak viremia. At 46 days p.i., thymus size and cell co mposition rebounded and supported increased productive infection. In contra st, neonatal cats inoculated with FIV developed chronic thymus atrophy and degeneration, which was associated with decreasing productive infection and low-level viremia. CONCLUSIONS: The fetal thymus is uniquely vulnerable to acute, transient de pletion and high-level productive infection. The neonatal thymus is less vu lnerable to acute changes, and responds through progressive atrophy and dec lining productive infection. Reduced immune competence, as reflected by the failure to control virus replication, may contribute to the accelerated pr ogression of FIV and HIV infections in utero.