CELLULAR MECHANISMS OF FELINE IMMUNODEFICIENCY VIRUS (FIV)-INDUCED NEUROPATHOGENESIS

Elisabeth Zenger, Evelyn Tiffany-Castiglioni, and Ellen W. Collisson

Department of Medicine, UCSF AIDS Program, San Francisco General Hospital, University of California, San Francisco, California (Zenger) and the Departments of Veterinary Anatomy and Public Health (Tiffany-Castiglioni) and Pathobiology (Collisson), College of Veterinary Medicine, Texas A&M University, College Station, Texas.

Received 10/7/97 Accepted 10/23/97

3. A ROLE FOR MICROGLIA AND/OR MACROPHAGES?

Microglia, macrophages, and the derivative multinucleated cells have been identified as the major HIV expressing cells in the brain. However, the number of these cells is small relative to the widespread neuropathology. There have been few investigations of effects of FIV on microglia. In vitro FIV infection of microglia is relatively noncytopathic. FIV does not induce a significant release of inflammatory cytokines tumor necrosis factor-alpha (TNF-alpha), intereukin 1 (IL1), or IL 6 from infected microglia, although increased major histocompatibility complex (MHC) class II expression has been demonstrated (personal communication, S. W. Dow, University of Colorado Health Sciences Center).

These findings parallel the results of experiments examining similar parameters in HIV infected microglia. Interferon was not examined and cannot be ruled out as a contributor to the neurotoxicologic process because of its importance in viral infections and MHC class II expression. The neurotoxicologic contribution of upregulated MHC class II in the brain, outside upregulation of the immune response, is uncertain. Although a purported requirement for neurotropic lentiviruses, macrophage tropism is frequently determined to be lacking for FIV isolates from brain tissue (personal communication, T.W. Vahlenkamp, Utrecht University). Infections with the FIV-PPR molecular clone or a specific FIV-PPR mutant which has decreased macrophage tropism (DU-FIV-PPR) produce similar neurologic dysfunctions (8) and similar neuropathological profiles are observed in FIV-infected cats treated with a drug delivery system that prevents viral replication in macrophages (22). Despite widespread belief in the importance of macrophages and/or microglia in lentivirus-associated neuropathogenesis, there are likely to be other players of at least as much significance (19).