The FIV-infected cat: A model for lentivirus-induced placental immunopathology and reproductive failure

Placental HIV infections frequently result in infected newborns or miscarriage. Aberrant placental cytokine expression during HIV infections may facilitate transplacental viral transmission or pregnancy perturbation. The feline immunodeficiency virus (FIV)-infected cat is a model for HIV infections due to similarities in biology and clinical disease. The purpose of this study was to evaluate placental immunomodulator expression and reproductive outcome using the FIV-infected cat model. Kittens were cesarean-delivered from FIV-B-2542-infected and control queens near term; placental and fetal tissues were collected. Real time Reverse Transcriptase (RT)-PCR was used to measure expression of representative placental Th1 cytokines, interleukin-1beta (IL-1beta) and interferon-gamma (IFN-gamma), a Th2 cytokine, IL-10, and the chemokine receptor, CXCR4. On average, control queens delivered 3.4 kittens/litter, and one of thirty kittens (3.2%) was non-viable. FIV-infected queens produced an average of 2.7 kittens/litter, and nonviable kittens, including resorbed, arrested, and/or stillborn fetuses accounted for 60% of offspring. FIV was detected in fourteen of fifteen placentas (93%) and twenty-one of twenty-two fetuses (95%) using PCR. Two experimental animals failed to become pregnant after repeated breeding, and the uteri were confirmed to be positive for FIV. These data demonstrate that FIV infection compromises reproduction in cats. Placental immunomodulator expression did not differ significantly when placentas from infected cats were compared to those of control cats. However, elevated expression of Th1 cytokines (IFN-gamma and IL-1) and increased Th1/Th2 ratios (IL-1beta/IL-10) occurred in placentas from resorptions. Therefore, increased placental Th1 cytokine expression was associated with pregnancy failure in the FIV-infected cat.