Regression of feline immunodeficiency virus (FIV) infection was observed in seven of nine vertically infected kittens born to two chronically infected mother cats. Both provirus and nonmaternal FIV antibody were detected in all kittens by 4 weeks of age but only three of the seven kittens were positive by blood mononuclear cell coculture. Between 10 and 14 months of age blood mononuclear cells from each of the seven cats were negative at least once by polymerase chain reaction (PCR), but evidence of virus infection was detected by coculture and/or PCR in biopsied lymph node or bone marrow from five of the seven cats. Despite this evidence of persistent tissue provirus, antibody production did not persist in any of the cats beyond 1 year of age. All seven cats remained asymptomatic although CD4 and CD8 T cell counts were in the low normal range throughout the study. By contrast, two additional perinatally infected littermates that were persistently virus isolation positive developed rapid CD4 depletion and progressed to terminal immunodeficiency by 9 weeks of age. Thus FIV infection can be downregulated and/or sequestered to extremely low levels barely detectable with the assays available, although absolute clearance of virus may not occur. These observations are relevant to human immunodeficiency virus (HIV) infection in paralleling both the apparent "regression" of HIV infection reported in some perinatally infected infants and the low-level, apparently stable, infection established by attenuated simian immunodeficiency viruses.

Vertical transmission of feline immunodeficiency virus (FIV) was studied in cats infected with either of two FIV clinical isolates (FIV-B-2542 or FIV-AB-2771) prior to breeding and conception. Queens infected 4 to 30 months (mean = 14 months) prior to conception transmitted FIV to 59 of 83 (71%) kittens; 50.6% were virus positive on the day of birth. To examine potential routes of FIV transmission from mother to offspring, kittens were delivered via either vaginal or cesarean birth and nursed by either their virus-infected natural mothers or uninfected surrogate mothers. Comparison of FIV infection rates at birth with those at 6 months of age in kittens delivered by cesarean and surrogate raised demonstrated that late in utero transmission occurred in approximately 20% of kittens. Comparison of kittens nursed by FIV mothers with those by uninfected surrogate mothers demonstrated a 13.5% increase in infection rate of kittens exposed to milk-borne virus. Isolation of virus from 40% of maternal vaginal wash samples and the slightly greater infection rate in vaginally versus cesarean-delivered surrogate-nursed kittens suggested that intrapartum transmission may occur. In addition, we found that low maternal CD4 count (<200 cells per microl), longer duration of maternal infection (>15 months), and maternal symptoms of clinical immunodeficiency correlated with increased rates of mother-to-kitten FIV transmission, paralleling observations in human immunodeficiency virus-infected women. We conclude that FIV infection provides a model in which to explore aspects of human immunodeficiency virus vertical transmission and intervention difficult to address in human patients.

Development of feline immunodeficiency virus (FIV) infection in cats as a small animal model for lentiviral immunodeficiency disease has been hampered by the prolonged and variable disease course following experimental infection. To address this issue, we generated high-titer, unselected FIV stocks by pooling plasma from cats acutely infected with a subgroup C FIV isolate designated CABCpadyOOC (FIV-C-PGammer). Subsequent infection with this virus pool resulted in rapidly progressive, fatal disease in greater than 50% of infected cats. Accelerated FIV disease was characterized by rapid and progressive CD4+ T-cell loss, lymphadenopathy, weight loss, lymphoid depletion, and severe thymic atrophy. Mortality and rate of disease progression were affected by the age of each cat at infection and whether the virus source animal was in the acute or chronic stage of infection. The rapid FIV disease syndrome was consistently associated with systemic lymphoid depletion, clinical disease, and susceptibility to opportunistic infections, analogous to accelerated and/or terminal HIV-1 infection. The results of this study demonstrate that FIV infection is a valid small animal model for lentiviral immunodeficiency disease.