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Experimental Infection of Chimpanzees with Lymphadenopathy-Associated Virus

MMWR Morbidity and Mortality Weekly Report, August 03, 1984 / 33(30);442-3
Centers for Disease Control and Prevention


Evidence from two investigations indicates that the retrovirus etiologically linked to acquired immunodeficiency syndrome (AIDS) may infect chimpanzees (Pan troglodytes). In the first study, investigators from CDC and Emory University's Yerkes Regional Primate Research Center, Atlanta, Georgia, inoculated two chimpanzees with lymphadenopathy-associated virus (LAV) (1), one of two prototype retrovirus isolates etiologically associated with AIDS (2). Both animals were virologically and serologically negative before inoculation; both were injected simultaneously with concentrated virus and autologous lymphocytes that had been infected in vitro with LAV. Both animals were immunostimulated concomitantly by inoculation of diphtheria-tetanus toxoid and pneumococcal vaccine. One animal received human lymphocytes as an additional immunostimulant.

Six days after inoculation, a retrovirus identified as LAV by reverse transcriptase assay, direct immunofluorescence, p25 competitive radioimmunoprecipitation, and electron microscopy was identified from peripheral lymphocytes of both animals. The virus was isolated from both animals from six consecutive lymphocyte specimens obtained every 2-4 weeks. The most recent specimens were obtained more than 4 months after inoculation. Antibody to the major core protein (p25) of LAV was first detected 3 months after inoculation and was again present at 4 months. In both animals, five consecutive postinoculation T((4))/T((8)) ratio determinations have shown an apparent downward trend, although values are significantly below normal in only one. No clinical illness has been detected in the animals, and physical examinations have remained normal.

In the second study, investigators at the National Institutes of Health (NIH) and Southwest Foundation for Biomedical Research have found evidence of transmission of HTLV-III to two chimpanzees receiving human plasma from an individual with the lymphadenopathy syndrome. Evidence for infection includes anti-HTLV-III seroconversion, depression of T((4))/T((8)) ratios, and, in one animal, the development of severe, prolonged lymphadenopathy coincident with seroconversion. Reported by H McClure, DVM, B Swenson, DVM, F King, PhD, Yerkes Regional Primate Research Center, Emory University, Atlanta, Georgia; J-C Chermann, PhD, F Barre-Sinousi, PhD, L Montagnier, MD, Institut Pasteur, Paris, France; J Eichberg, Southwest Foundation for Biomedical Research, San Antonio, Texas; C Saxinger, R Gallo, National Cancer Institute; H Alter, H Masur, A Macher, Clinical Center, C Lane, A Fauci, National Institute of Allergy and Infectious Diseases, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland; Div of Viral Diseases, Div of Host Factors, Center for Infectious Diseases, CDC.

Editorial Note

Editorial Note: Primate transmission experiments have been under way at CDC and NIH for some time. LAV and HTLV-III, as well as human AIDS tissue, have been inoculated into several species of primates, including marmosets, rhesus monkeys, and chimpanzees. Except for some lymphocyte changes (3), no disease or infection has been previously reported. The studies reported here indicate that LAV/HTLV-III can be transmitted to chimpanzees both by inoculating virus isolates and human plasma. In some instances, immunologic abnormalities and prolonged lymphadenopathy have followed inoculation, but opportunistic infections or tumors characteristic of AIDS have not developed. Transmission of HTLV-III from lymphocyte-poor human plasma is consistent with reports of AIDS among recipients of plasma or anti-hemophilic concentrates made from pooled plasma (4,5).

The virus isolated from the LAV-inoculated chimpanzees was morphologically and immunologically identical to LAV. Virus particles were morphologically distinct from the Type D retrovirus etiologically implicated in "simian AIDS," a transmissible syndrome of macaques (6,7).

Long-term follow-up of the LAV and HTLV-III-infected chimpanzees, as well as other primates, is continuing. Careful examination of the interaction between infection and host response in primates could clarify the pathogenesis of AIDS in humans.

References

  1. Barre-Sinoussi F, Chermann JC, Rey F, et al. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science 1983;220:868-71.

  2. Gallo RC, Salahuddin SZ, Popovic M, et al. Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and at risk for AIDS. Science 1984;224:500-3.

  3. Gajdusek DC, Amyx HL, Gibbs CJ, et al. Transmission experiments with human T-lymphotropic retroviruses and human AIDS tissue. Lancet 1984;I:1415-6.

  4. Curran JW, Lawrence DN, Jaffe HW, et al. Acquired immunodeficiency syndrome (AIDS) associated with transfusions. N Engl J Med 1984;310:69-75.

  5. Evatt BL, Ramsey RB, Lawrence DN, Zyla LD, Curran JW. Acquired immunodeficiency syndrome in hemophilia patients. Ann Int Med 1984;100:495-8.

  6. Marx PA, Maul DH, Osborn KG, et al. Simian AIDS: isolation of a type D retrovirus and transmission of the disease. Science 1984;223:1083-6.

  7. Letvin NL, Aldrich WR, King NW, et al. Experimental transmission of macaque AIDS by means of inoculation of macaque lymphoma tissue. Lancet 1983;II:599-602.

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