Experimental Infection of Chimpanzees with
Lymphadenopathy-Associated Virus
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
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.
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.
Gajdusek DC, Amyx HL, Gibbs CJ, et al. Transmission
experiments
with human T-lymphotropic retroviruses and human AIDS tissue.
Lancet 1984;I:1415-6.
Curran JW, Lawrence DN, Jaffe HW, et al. Acquired
immunodeficiency syndrome (AIDS) associated with transfusions.
N
Engl J Med 1984;310:69-75.
Evatt BL, Ramsey RB, Lawrence DN, Zyla LD, Curran JW. Acquired
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Marx PA, Maul DH, Osborn KG, et al. Simian AIDS: isolation of
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type D retrovirus and transmission of the disease. Science
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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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