Molecular biology of the feline immunodeficiency virus auxiliary genes.

Introduction Feline immunodeficiency virus (FIV) causes a slowly progressive multiorgan disease in infected cats and shows considerable pathogenic similarities to the human immunodeficiency virus type I (HIV-1i), the causative agent of AIDS (Miyazawa & Mikami, 1993; Pedersen et al., 1987; Yamamoto et al., 1988). It is therefore considered a useful small-animal model for HIV-l-induced AIDS studies. FIV belongs to the family Retroviridae, a group of small, enveloped positive-strand RNA viruses, These viruses have an enzyme, reverse transcriptase, which enables them to replicate their RNA genome through a DNA intermediate (Coffin, 1992). FIV is a member of the genus Lentivirus and is closely related in biological characteristics and genome organization to other mammalian lentiviruses, including HIV, simian immunodeficiency virus (SIV), bovine immunodeficiency-like virus (BIV), equine infectious anaemia virus (EIAV), visna virus and caprine arthritis-encephalitis virus (CAEV) (Narayan & Clements, 1990). The genome of simple retroviruses contains three long open reading frames (ORFs) coding for the Gag, Pol and Env proteins, which constitute their structural and enzymatic repertoire and are packaged in the progeny virions. In addition to these structural ORFs, lentiviruses have several additional auxiliary ORFs that characterize this virus group. There have been significant advances recently in the study of lentiviruses and it is now believed that these auxiliary ORFs play an important role in the distinctive features of lentivirus infection, virus persistence in the face of host immune responses and induction of chronic disease. The HIV-1 genome also has six accessory genes and their functions have been studied extensively by molecular biological analyses. Of these, two transactivator genes, tat and rev, are essential for virus gene expression (Felber & Pavlakis, 1993). Although nefis not essential for replication of the virus, it may have important functions in the virus life-cycle (Miller