COlVIlVIENT Letter BaEV Is a relic from an ancient retrovirus that crossed species barriers R etrovirus-related sequences [e.g. SINEs (short interspersed nuclear elements), LINEs (long interspersed nuclear elements), retrotransposons and endogenous retroviruses] make up more than 10% of a mammalian genome. In fact, it can be stated that these sequences of reverse-transcribed origin have shaped the mammalian genome. The evolution of these elements are therefore of general interest to both virologists and geneticists. In this research field, the question of which came first still remains; are endogenous retroviruses remnants of exogenous retroviruses that became extinct!, or do new infectious retroviruses originate from endogenous retroviruses as a result of activation and/or recombination events 2 ? In their recent paper on baboon endogenous virus (BaEV) evolution and ecology, van der Kuyl et al. 3 review the evidence for a past history of exogenous retroviral cross-species transmission among non-human primate species with shared habitats. Their evidence is based on the phylogenetic analysis of BaEV sequences in several monkey species, in comparison with the phylogenetic relationship among the species. This Horizons From mitosis to apoptosls T cells interact with B cells to in• duce clonal proliferation and antibody secretion in the presence of foreign antigen, and B cells that bind self antigens are usually deleted. The fate of B cells is decided by the joint action of two surface ligands on activated T cells, C040L and FasL (both members of the tumor necrosis family), and mediated by signals from the B-cell antigen re• ceptor (BCR). Foreign antigens trig• ger C040L and FasL to promote proliferation, and clonal deletion is triggered when the BCR is de• sensitized by chronic stimulation by self antigens. Fas and FasL may limit mitogenic signals from T cells to tolerant B cells by inducing apop• to sis in these B cells; thus, when tolerant B cells present antigen to analysis is strikingly similar to the phylogenetic relationship between human immunodeficiency virus (HN) and simian immunodeficiency virus (SIV) strains4, and to the analysis of human T cell leukemia virus type I (HTLV-I) and simian T cell leukemia virus type I (STL V -I) cross-species transmissions 5 ,6, which means that cross-species transmission of primate retroviruses is common rather than exceptional. These data support the view that at least BaEV has existed as an exogenous virus in the past .. It is likely that most endogenous retroviruses are exogenous retroviruses that have almost 'frozen', in comparison with the high evolutionary rate of exogenous retroviruses, by integrating into the germline. This does not preclude the possibility that endogenous viruses can become exogenous again: a pressing issue for initiatives in the field of xenotransplantation. It is of interest to notice that the replication and infection properties of the exogenous human and simian (i.e. primate) T cell leukemia viruses (PTL Vs) resemble those of endogenous retroviruses; their evolutionary rate is very lowS,6, they C04+ T cells, they are eliminated rather than proliferate. If T cells carry defective Pas or CD40, as oc• curs in some inherited disorders, such as Evans syndrome, then large amounts of autoantibodies are pro• duced. Both ligands are required to decide B-cell fate, and the tim• ing of BCR stimulation by antigen is the important cue. Ingeniously, Rathmell and colleagues used hen egg lysozyme, both as a foreign anti• gen and as a transgenic 'self antigen', which tolerized mice by continuous regulation of BCR. Rathmell,J.C. etal. (1996) Expansion or elimination of B cells in vivo: dual roles for CD40- and Fas (CD95)-ligands modulated by the B cell antigen recep• tor, Cell 87, 319-329 spread within a host by clonal expansion rather than recombination 7 ,8, and viral transmission is linked to the transfer of infected cells, as free virus is almost non-infectious 9 • Thus, we may just be witnessing a transition from an exogenous to an endogenous retrovirus. Anne-Mieke Vandamme Rega Institute for Medical Research and University Hospitals, Minderbroedersstraat 10-12, B-3000 Leuven, Belgium References 1 Coffm,j.M. (1993) in Reverse Transcriptase (Skalka, A.M. and Goff, S.P., eds), pp. 445-479, Cold Spring Harbor Laboratory Press 2 Doolittle, R.F. et al. (1989) Q. Rev. BioI. 64, 1-30 3 van def Kuyl, A.C., Dekker, J.T. and Goudsmit,J. (1996) Trends Microbial. 4, 455-459 4 Sharp, PM. et al. (1994) AIDS 8, S27-S42 5 Liu, H-F. (1996)}. Gen. Virol. 77, 359-368 6 Vomdamme, A-M. (1996)}. Gen. Vlrol. 77, 1089-1099 7 Prince, H.E. and Swanson, P. (1993) }. Infect. Dis. 168, 1599-1600 8 Wattel, E. et al. (1995) J. Virol. 69, 2863-2868 9 Kuroda, M.j. et al. (1992) Intervirology 34,202-212 More animal madness I n a group of 416 neuropsychi• atric patients in Germany, 9.6% were found to have evidence of Borna disease virus (BOV) infection. Sera from the patients recognized the p40 antigen of the virus, which is highly conserved among virus iso• lates from several species of mam• mal. BDV causes central nervouS system (CNS) disease and behav• ioural abnormalities in a wide range of animal species, and it could be that humans are vulnerable to zoonotic infection by this virus. Sauder, C. et al. (1996) Detection of Borna disease virus (BDV) antibodies and BDV RNA in psychiatric evidence for high sequence conservation of human blood-derived BDV RNA, ,. Viro!' 70, 7713-7724 Copyright © 1996 ElseVIer Science Ltd. All rights reserved. 0966 842X1961$15.00 TRENDS IN MICROBIOLOGY 478 VOL. 4 No. 12 DECEMBER 1996