Department of Microbiology, Pathology, and Parasitology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA
Feline immunodeficiency virus is a lentivirus of felids that causes a persistent infection of cells in the immune system.1 Onset of recognizable disease in domestic cats ranges from months to years. Clinical signs are often non-specific and include wasting, chronic gingivitis, anorexia and behavioral changes. During the asymptomatic period, CD4:CD8 ratios are low or inverted, either due to a decline in the helper T lymphocyte population, CD4, or an increase in the cytotoxic/suppressor T lymphocyte population, CD8. With time, the changes in CD4 and CD8 lymphocyte subsets impair the ability of the infected host to mount appropriate immune responses to FIV and other infectious agents.
Controversy exists about whether FIV has an adverse impact on the health of African lions. Recent experiences with captive, FIV seropositive lions in several institutions suggests that it can. This study uses three-color flow cytometric analysis to examine CD4 and CD8 lymphocytes in cryopreserved peripheral blood mononuclear cells from captive and free-ranging lions to determine if changes in T lymphocyte subsets analogous to the domestic cat occur. Antibody status was confirmed by ELISA and western blot for all lions. Seropositive, free-ranging lions (n=17) were collected from Kruger National Park and seronegative lions from Etosha and Hluhluwe-Umfolozi National Parks (n=27). Captive lions (n=5) took up to 2 yr to seroconvert following introduction of a FIV seropositive male in 1990. Flow cytometry was performed on these animals from 1994–1999.
Overall, free-ranging, FIV seropositive lions have lower CD4:CD8 ratios than their seronegative counterparts. When examined by age class, there is no significant difference in CD4:CD8 ratios between seropositive and seronegative lions ≤4 yr of age. However, there is a significant difference for the 5–8 yr age classes and all FIV seropositive lions older than 8 yr have inverted CD4:CD8 ratios. Decreasing and inverted ratios are the result of an increase in CD8 lymphocytes which possess a suppressor phenotype observed in FIV-infected domestic cats.2 This suppressor cell population is thought to inhibit virus replication, thereby contributing to the prolonged asymptomatic period. When the host’s immune system no longer contains virus replication, then clinical decline begins.
Inverted CD4:CD8 ratios are first observed in captive, FIV seropositive lions 4–6 yr following exposure to FIV. Although the CD8 suppressor phenotype is elevated in these lions compared to their negative captive counterparts, CD4 lymphocyte numbers are significantly decreased throughout the study period and contribute to the inverted ratios. All the captive, FIV seropositive lions have experienced a severe decline in total T lymphocytes. Three of the five lions have been euthanatized during the past 3 yr because of deterioration in condition.
To summarize, FIV does have an impact on T lymphocyte subsets of both free-ranging and captive African lions, similar to that observed in the domestic cat. Assuming that free-ranging lions are infected early in life and based on the length of post-exposure to FIV in the captive animals, CD4 and CD8 lymphocyte subsets alter over time with significant changes occurring at least 4 yr post-infection. Lions are consequently at risk for developing complications associated with FIV.
This work was supported in part by a grant from Ralston Purina Big Cat Survival Fund. Numerous individuals were instrumental in providing samples. We wish to thank the veterinarians and staff at the North Carolina Zoological Park for annual sampling of their FIV seropositive populations and Dr. Rebecca Yates and the Wildlife Waystation Health Center for supplying samples from seronegative lions. Drs. Mitch Bush and Cobus Raath made it possible to collect samples from lions in Kruger National Park; Dr. Mike Briggs and the Brookfield Zoological Society made it possible to collect samples from lions in Etosha; and Drs. Craig Packer, Woody Meltzer, and Dave Cooper made it possible to collect samples from lions in Hluhluwe-Umfolozi.
1. Kennedy-Stoskopf, S. 1999. Emerging viral infections in large cats. In: Fowler M.E., Miller R.E. eds. Zoo and Wild Animal Medicine, Current Therapy 4. WB Saunders Co., Philadelphia, Pennsylvania, Pp. 401–410.
2. Bucci J.G., D.H. Gebhard, T.A. Childers, R.V. English, M.B. Tompkins, and W.A.F. Tompkins. 1998. The CD8+ cell phenotype mediating antiviral activity in feline immunodeficiency virus-infected cats is characterized by reduced surface expression of the CD8 beta chain. J. Infect. Dis. 178:968–977.