Nonhuman primates as animal models for human disease

Primates arc widely used as models for studying HIV infection of humans. Although HIV does not infect all of the different species of nonhuman primates, it does infect chimpanzees. Thus far, however, there are few documented cases of chimpanzees succumbing to HIV-induced pathogenesis despite several chimpanzees having been infected for over 10 years with the virus. Therefore, combined with their endangered status, the use of chimpanzees is hardly practical for the study of HIV infection in humans. SIV infection of the rhesus macaque (Macaca mulatto), however, has proved to be a very effective animal model for studying HIV pathogenesis in humans. Due to the nucleotide sequence similarity between HIV and SIV and the similar course of disease progression between humans and rhesus macaques, SIV infection in rhesus macaques is widely-used as an animal model of HIV infection in humans. More importantly, the immune systems of humans and rhesus monkeys have been found to bind and present peptides derived from very similar regions of HIV and SIV, respectively. Therefore, this animal model will be especially useful for conducting vaccine trials which cannot be carried out in humans.

Nonhuman primates have also been used to study the pathogenesis and immune response to other viruses. Many of the New World primate species were extensively used to study the pathogenesis of viral infections in the early 1970s and 1980s due to their extreme susceptibility to these diseases. In particular, the cotton-top tamarin has been used to test vaccines for Epstein-Barr virus (EBV). Interestingly, the tamarin is susceptible to EBV-induced lympho-proliferative tumors upon inoculation with EBV whereas many of the other New World primate species are not susceptible to EBV. Owl monkeys, for example, develop a typical lymphocytosis similar to that seen in humans after infection with EBV. Rhesus macaques have also been used to study a variety of autoimmune diseases. These include experimental EAE and CIA. EAE can be induced in rhesus monkeys and the common marmoset by injection of whole brain homogenates or purified myelin basic protein. Also, rhesus macaques injected with collagen readily develop a disease that resembles rheumatoid arthritis. Thus, these animals can be used to understand the pathogenesis of this disease and can be used to test therapeutic modalities.

The similarities between human MHC molecules and those of nonhuman primates has facilitated a variety of transplantation-related studies. In particular, the rhesus macaque has been widely used to determine whether tolerance can be induced prior to organ transplantation. By manipulating the immune system, tolerance to kidney transplants was found to be dramatically increased in rhesus monkeys. Therefore, nonhuman primates provide preclinical large-animal models to determine whether studies conducted in mice can be extended into clinical applications in humans.

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