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Unique Susceptibility of the Fetal Thymus to Feline Immunodeficiency Virus Infection: An Animal Model for HIV Infection In Utero

Authors

  • CALVIN M. JOHNSON,

  • P. CYNTHIA CRAWFORD,

  • GEORGE P. PAPADI,

  • SANDRA J. BORTNICK


Address reprint requests to Calvin M. Johnson, Department of Pathobiology, PO Box 110880, College of Veterinary Medicine, University of Florida, Gainesville, FL 32611-0880.
E-mail: johnsonc@mail.vetmed.ufl.edu

Abstract

PROBLEM: 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.
METHOD OF STUDY: 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.

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