FELINE IMMUNODEFICIENCY VIRUS AS A MODEL FOR DEVELOPMENT OF MOLECULAR APPROACHES TO INTERVENTION STRATEGIES AGAINST LENTIVIRUS INFECTIONS

All model systems have certain limitations, because the conditions of immunological responsiveness and/or drug tolerance and metabolism may differ from those found in humans. However, every model has unique advantages, and each system will yield useful information regarding the treatment at hand. With the spread of the acquired immunodeficiency syndrome (AIDS) epidemic, driven by the spread of the causative agent, human immunodeficiency virus (HIV), it has become necessary to develop model systems relevant to the treatment of lentivirus infections. Nonhuman primates offer valuable systems for study. The most prominent and feasible primate model is the simian immunodeficiency virus (SIV) infection of rhesus macaques. Both HIV-1 and SIV use a common receptor, CD4, and host cell ranges are similar for the two viruses. Therefore, drug approaches that interrupt receptor interactions may be developed, using SIV as a model system. On the other hand, adult macaques have failed as a useful model for testing drug treatments, such as AZT, probably due to the differential metabolism of the drug. The chimpanzee primate model is closer to humans and is more useful in that; these primates are infectable by HIV directly. However, no disease has been observed and it may be that if any disease is caused at all, the latency will be similar to the decade-long time for the development of AIDS in humans. In addition, chimpanzees are an endangered species and expensive to maintain, and are thus impractical for extensive preliminary testing. There are numerous nonprimate lentiviruses that may serve admirably in the development of intervention strategies effective against HIV. The smallest and most easily manipulable natural model is feline immunodeficiency virus (FIV), a lentivirus found associated with a debilitating immunodeficiency syndrome in cats, similar to AIDS associated with HIV infection of humans. The purpose of this chapter is to report the genomic structure of FIV as it is currently known and to compare it with the structure of HIV. It is clear that there is substantial genomic diversity between these two lentiviruses that negates the utility of FIV for certain intervention approaches. However, it is equally clear that the similarities in the life cycle of HIV and FIV, as well as commonalities in particular structural motifs make FIV an attractive model for comparative study. © 1995, Academic Press Inc.