ATLANTA September 13, 2000 - Three HIV-positive chimpanzees that are progressing to AIDS could provide insight into how the disease develops and might be averted, according to research conducted at the Yerkes Regional Primate Research Center of Emory University and published in the October issue (Vol. 182, No. 4) of The Journal of Infectious Diseases.
The chimpanzees were originally inoculated with multiple strains of HIV some 15 years ago. All of the animals remain clinically healthy, but show evidence of abnormal immune function typical of progressive HIV infection.
Although chimpanzees are susceptible to HIV infection, they normally do not develop AIDS. In 1996, Dr. Francis Novembre and other scientists at the Yerkes Research Center described the first case of AIDS ever reported in a chimpanzee. That animal (C499) was housed with other HIV positive chimpanzees, including two of the three chimpanzees that are currently progressing to AIDS. Yerkes scientists are conducting genetic analyses to determine whether C499 transmitted his particular subtype of HIV to his companions.
The progressor chimps are among a group of ten HIV-positive chimpanzees that have been regularly monitored since the mid-1980s. Six of the chimps have displayed stable chronic HIV infection without signs of progressing to AIDS. C499 was euthanized in 1996 after developing complications from AIDS.
The Yerkes team, led by Dr. Shawn O'Neil, has found that virologic and immunologic changes among the progressor chimpanzees closely resemble those seen in human progressors, most notably high viral loads and profound reductions in CD4+ T lymphocytes. Likewise, the progressor chimpanzees have displayed evidence of chronic immune activation, another key marker of HIV progression in people.
"The conspicuous absence of immune activation in most HIV-infected chimpanzees has been proposed to explain the relative resistance of this species to the development of AIDS," said O'Neil. "These data suggest that chronic immune activation is important for HIV pathogenesis in chimpanzees, as it is in people."
Scientists believe that chimpanzees serve as the natural reservoir for HIV, and that they have adapted to HIV infection and developed resistance to the virus through natural selection. The HIV pandemic is thought to have originated through cross-species transmission of HIV from chimpanzees to people in West Africa. According to O'Neil, the discovery of the three progressor chimps presents an unique opportunity to identify the evolutionary mechanisms that normally protect chimpanzees from AIDS a mystery that continues to elude scientists.
"Aside from humans, chimpanzees are the only animals that are consistently susceptible to HIV infection," explained O'Neil. "But in most studies, chimpanzees have not developed AIDS. This group of progressor chimpanzees provides an important yardstick against which we can compare long-term nonprogressor (LTNPs) chimps. If we can determine what is different about these three chimps, we may be able to determine what normally protects these animals from AIDS."
O'Neil believes such a finding could have significant implications for the development of an HIV vaccine and new treatments for AIDS. Despite the scientific value of the progressor chimpanzees, O'Neil said that there are no plans to infect additional chimpanzees.
Like most chimpanzees, a small cohort of HIV-positive people do not develop AIDS. Compared to those who progress to AIDS, LTNP people generally maintain substantially lower levels of virus in plasma, normal, stable numbers of CD4+ T cells, and vigorous antiviral immune responses.
Yerkes scientists, however, have identified a compelling contrast between LTNP chimpanzees and LTNP people. LTNP chimpanzees maintain normal numbers of T-cells and levels of immune activation comparable to HIV-negative chimps. Human LTNPs, on the other hand, have an elevated level of immune activation compared to people who are HIV negative.
"This discrepancy could reflect fundamental differences in the mechanisms used to control HIV infection between an evolutionarily adapted host and an outlier population of a non-adapted host," said O'Neil.
The Yerkes Regional Primate Research Center holds to strict standards of care and treatment of animals established by the United States Department of Agriculture, National Institutes of Health, and professional oversight bodies. Personnel who work with HIV-infected chimpanzees also follow established biohazard guidelines to ensure their safety.
In addition to O'Neil and Novembre, authors of the Yerkes study that appeared in The Journal of Infectious Diseases include Drs. Clyde Hart, Daniel Anderson, James Herndon, and Harold McClure. Additional authors were Anne Brodie Hill, Carolyn Suwyn, Tammy Evans-Strickfaden, and Michelle Saucier.
The full text of the study is available at: http://www.emory.edu/WHSC/YERKES/newsroom/oneil.pdf.
The research was funded by the National Institutes of Health.
Journal
The Journal of Infectious Diseases