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Keywords:

  • Feline immunodeficiency virus;
  • HIV animal model;
  • placental immunopathology

Problem

Pediatric human immunodeficiency virus (HIV) infection is largely a result of transplacental transmission, and pregnancy perturbation is more frequent in HIV-infected women. Dysregulation of placental immunology may occur during HIV infection, possibly facilitating HIV vertical transfer and miscarriage. The (FIV)-infected cat is a useful small-animal model for HIV pathogenesis because the viruses share common biological and clinical features. Transplacental transmission is readily achieved experimentally, resulting in a high proportion of infected offspring and frequent reproductive failure.

Method of study

We are using this model to examine lentivirus-induced placental immunopathology to determine the role aberrant immunology plays in intrauterine transmission and pregnancy perturbation.

Results

Kittens were cesarean delivered from FIV-B-2542-infected and control queens at week 8 gestation (1 week short of term), and placental and fetal specimens were collected. On average, control queens delivered 3.8 kittens/litter, and 1 of 31 kittens (3.2%) was non-viable. FIV-infected queens produced 2.7 kittens/litter with 15 of 25 fetuses (60%) non-viable. The virus was detected in 14 of 15 placentas (93%) and 21 of 22 fetuses (95%) using polymerase chain reaction (PCR). Using a one-step, real time reverse transcriptase (RT)–PCR, we measured expression of representative placental T helper 1 (Th1) cytokines, interleukin (IL)-1β and interferon (IFN)-γ, a Th2 cytokine, IL-10, and chemokine receptor CXCR4. A comparison of placental cytokine expression between infected and control queens did not reveal differences between the two groups. However, elevated expression of Th1 cytokines and increased Th1/Th2 ratios (IL-1β/IL-10) occurred in placentas from resorptions, indicating that increased placental Th1 cytokine expression was associated with pregnancy failure in the FIV-infected cat.

Conclusion

The potential to establish efficient FIV in utero transmission, coupled with the parallels in immunopathology between FIV-infected cats and HIV-infected humans, suggests the usefulness of the FIV-infected cat as a cost-effective, small-animal model to study lentivirus-induced immunopathology, transplacental infection, and reproductive failure.