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Simian Aids Provides a Useful Model

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Simian Aids Provides a Useful Model © 1986 Nature Publishing Group http://www.nature.com/naturebiotechnology SAIDS SYMPOSIUM SIMIAN AIDS• PROVIDES A USEFUL MODEL DA VIS, Calif.-The chimpanzee is still the only non-human species gag env known to be susceptible to infection SRV-1 '----- -' prt c..___ _ ..._,l-sorf with the human immunodeficiency 91... __P_ o_i __...J virus (HIV). However, at least two separate subfamilies of retroviruses gag env e:::JPrl (SRV and SIV) are capable of causing HTLV- II pol immunosuppression in macaques. 0 Studies of AIDS pathogenesis, treat­ ment, and immunoprotection can use TAT each of these animal models. This was gag orfA I clear from the presentations of scien­ HIV pol env fy-orfB tists from the seven United States Po, prt ART Primate Centers and other institu­ tions in the U.S.A. and abroad who met here late in September to discuss 0 2 3 4 5 6 7 8 9 Kb simian AIDS (SAIDS). Investigators from the Southwest Genetic organization of several retroviruses. Open reading frames corresponding to Foundation (Texas), Yerkes (with the viral genes are labeled for SRV-1 (SAIDS type D retrovirus-serotype I), human T-cell Centers for Disease Control, Geor­ lymphotropic virus Type II (HTLV-11), and the human immunodeficiency virus gia), and the Frederick Cancer Re­ (HIV). See text for a description of how simian retroviruses are being studied as search Center at the National Insti­ models for human AIDS. tutes of Health (Maryland) reported results on HIV infection or immuni­ and the National Institutes of Health Like its human counterpart, SIV zation of chimpanzees. Although al­ reported their experience with replication is largely restricted to T4 most all HIV-inoculated chimps are SAIDS type D retrovirus (SRV) in lymphocytes, but it does not appear persistently infected and mount an several species of macaques. SRV is as genetically diverse. Isolates from immune response similar to that of closely related to the prototype type the various centers are quite similar humans, no AIDS-like disease has de­ D retrovirus-the Mason-Pfizer mon­ by criteria such as restriction map­ veloped as of two years after infec­ key virus. Although immunologically ping, peptide mapping, and amino tion. While scientists can recover the unrelated to HIV, SRV provides an acid sequencing. Cloned SIV shows virus from peripheral blood lympho­ excellent model for studying the varying degrees of nucleotide homol­ cytes and bone marrow, they have mechanisms ofretroviral-induced im­ ogy with HIV. The most, about 50 been unable to isolate it from plasma, munosuppression. percent, is found in the gag and pol saliva, or cerebral spinal fluid. And At the three West Coast centers, genes. Of particular interest are HIV none of the chimps has yet developed SR V and its associated diseases are isolates called HTLV-IV, which were signs of central nervous system infec­ highly prevalent and account for a obtained from healthy West African tion. significant mortality in the macaque prostitutes, and appear very similar Experiments to investigate trans­ colonies. At the Wisconsin and New to SIV by restiction enzyme analysis mission routes show that oral expo­ England centers, the virus represents and immunological cross-reactivity. sure to cell-free HIV does not cause a less acute problem, and it appears to SIV can be experimentally transmit­ infection of chimps, whereas vaginal be absent from the Delta (Louisiana) ted in macaques and induces a per­ exposure succeeds in establishing in­ and Yerkes (Georgia) centers. Differ­ sistent infection characterized by a fection. The virus is not spread by ent manifestations of SAIDS are asso­ humoral antibody response and mild simple cage contact, but animals in­ ciated with two distinct serotypes, immunosuppression. Although pass­ .fected with one strain of HIV can be SRV-1 and SRV-2. Each has been sage of SIV in human T cells appears superinfected with a different strain molecularly cloned and sequenced, to rapidly attenuate its virulence, ini­ of the virus. This supports the idea and the cloned California type D iso­ tial attempts to immunize against ex­ that when a human vaccine is devel­ late (SRV-1) has been used to induce perimental infection using an inacti­ oped, it will need to be multivalent. SAIDS. Resistance to infection with vated virus vaccine have been unsuc­ A number of groups have used this virus is correlated with the pres­ cessful. Nevertheless, infection of HIV envelope proteins to induce a ence of neutralizing antibodies, and macaques with SIV promises to be vigorous humoral or cellular anti­ an inactivated whole virus vaccine is another useful model for pathogene­ body response (including neutraliz­ effective in preventing experimental­ sis, treatment, and prevention of a ing antibodies) in chimps and ma­ ly induced disease. retroviral-induced, AIDS-like dis­ caques. These envelope antigens are Researchers at the New England, ease. derived from genetically engineered Delta, Yerkes, California, and Wash­ In order to make the most of the gpl20, synthetic peptides from gp4 l ington centers are studying another opportunities afforded by these ani­ and gpl20, recombinant vaccinia vi­ simian virus that is more closely relat­ mal models, cooperation and sharing rus expressing gp4l and gpl20, and ed to HIV. SIV (STLV-111), a lenti­ of reagents and other resources native gpl20 obtained from HIV par­ virus, is highly prevalent in healthy among the different primate centers ticles. Whether any of the prepara­ HIV-seropositive sooty mangabeys in is of the utmost urgency. In this vein, tions will afford protection from HIV primate centers and zoos. It is found the California center has established a challenge remains to be determined. less frequently in healthy African reference unit to help monitor the Investigators at five primate cen­ green monkeys (from Africa, not the seroepidemiology of SAIDS and its ters (California, Oregon, Washing­ Caribbean) and, in low prevalence, in associated retroviruses. ton, Wisconsin, and New England) immunosuppressed macaques. -Murray Gardner BIO/TECHNOLOGY VOL 4 DECEMBER 1986 1053 .
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