Unique susceptibility of the fetal thymus to feline immunodeficiency virus infection: an animal model for HIV infection in utero.
OBJECTIVE
Human infants infected in utero with HIV develop thymus insufficiency and progress to AIDS sooner than infants infected peripartum. However, direct analysis of the thymus is difficult due to limited tissue access and variable timing of vertical transmission.


METHODS
Fetal and neonatal cats were inoculated with feline immunodeficiency virus (FIV) at an equivalent infectious dose. The thymus, blood, and lymph nodes were harvested and compared at 23 and 46 days post-inoculation (p.i.) and also compared to sham-inoculated, age-matched controls. Lymphocyte phenotypes were analyzed by flow cytometry and virus burden was quantified 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 composition rebounded and supported increased productive infection. In contrast, 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 depletion and high-level productive infection. The neonatal thymus is less vulnerable to acute changes, and responds through progressive atrophy and declining productive infection. Reduced immune competence, as reflected by the failure to control virus replication, may contribute to the accelerated progression of FIV and HIV infections in utero.
Johnson
C M
CM
Department of Pathobiology, College of Veterinary Medicine, University of Florida, Gainesville 32610-0880, USA. johnson@mail.vetmed.ufl.edu
Bortnick
S J
SJ
Crawford
P C
PC
Papadi
G P
GP
D000818:Animals; D000831:Animals, Newborn; D001284:Atrophy; D002415:Cats; D004195:Disease Models, Animal; D016181:Feline Acquired Immunodeficiency Syndrome / Q000150:complications / Q000209:etiology* / Q000276:immunology / Q000821:virology; D005260:Female; D005333:Fetus / Q000276:immunology / Q000821:virology*; D015658:HIV Infections / Q000209:etiology* / Q000276:immunology; D006706:Homeostasis; D006801:Humans; D016089:Immunodeficiency Virus, Feline / Q000502:physiology; D007231:Infant, Newborn; D008954:Models, Biological; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology / Q000821:virology; D013601:T-Lymphocytes / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology / Q000473:pathology / Q000821:virology*; D014766:Viremia / Q000209:etiology; D014779:Virus Replication