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
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.