Macaque Models of Human Infectious Disease

Abstract

Macaques have served as models for more than 70 human infectious diseases of diverse etiologies, including a multitude of agents-bacteria, viruses, fungi, parasites, prions. The remarkable diversity of human infectious diseases that have been modeled in the macaque includes global, childhood, and tropical diseases as well as newly emergent, sexually transmitted, oncogenic, degenerative neurologic, potential bioterrorism, and miscellaneous other diseases. Historically, macaques played a major role in establishing the etiology of yellow fever, polio, and prion diseases. With rare exceptions (Chagas disease, bartonellosis), all of the infectious diseases in this review are of Old World origin. Perhaps most surprising is the large number of tropical (16), newly emergent (7), and bioterrorism diseases (9) that have been modeled in macaques. Many of these human diseases (e.g., AIDS, hepatitis E, bartonellosis) are a consequence of zoonotic infection. However, infectious agents of certain diseases, including measles and tuberculosis, can sometimes go both ways, and thus several human pathogens are threats to nonhuman primates including macaques. Through experimental studies in macaques, researchers have gained insight into pathogenic mechanisms and novel treatment and vaccine approaches for many human infectious diseases, most notably acquired immunodeficiency syndrome (AIDS), which is caused by infection with human immunodeficiency virus (HIV). Other infectious agents for which macaques have been a uniquely valuable resource for biomedical research, and particularly vaccinology, include influenza virus, paramyxoviruses, flaviviruses, arenaviruses, hepatitis E virus, papillomavirus, smallpox virus, Mycobacteria, Bacillus anthracis, Helicobacter pylori, Yersinia pestis, and Plasmodium species. This review summarizes the extensive past and present research on macaque models of human infectious disease.

Macaque Proteome Response to Highly Pathogenic Avian Influenza and 1918 Reassortant Influenza Virus Infections

“…While rodent model systems have been developed to study influenza virus infection (8), genetic and physiological differences compared to humans argue for a more physiologically relevant model (9). In light of this, several macaque species, including Macaca mulatta, Macaca nemestrina, and Macaca fascicularis, currently serve as physiologically relevant model systems for studying pathogenesis induced by human viruses, encompassing agents such as HIV, Ebola, variola major, and influenza A viruses (1,12). Additionally, the recent completion of the rhesus macaque sequencing project (14) and continuing sequencing efforts for other macaque species now make this primate a particularly amenable system for in-depth global genetic and proteome-based studies.…”

Pathology of Experimental Machupo Virus Infection, Chicava Strain, in Cynomolgus Macaques (Macaca fascicularis) by Intramuscular and Aerosol Exposure

“…As these nonhuman primates mount similar immunologic and physiologic responses to humans, cynomolgus macaques are effective animal models of disease. 9,11 In this study, we assessed whether the MACV Chicava strain would be lethal in macaques and whether the disease course and lesion development are analogous to that seen in humans. The Chicava strain was selected for this work as this strain was isolated without passage in animals and is currently used in guinea pig models.…”

Rhesus Macaque Inhibitory and Activating KIR3D Interact with Mamu-A–Encoded Ligands

“…Complex genetic configurations of KIR and MHC class I are also encountered in nonhuman primates such as rhesus macaques (20)(21)(22), which are very important nonhuman primate models of human infectious and autoimmune diseases, in vaccine development, and in transplantation research (23). Yet, despite their importance in biomedical research, the NK cell biology and genetics of rhesus macaques are only poorly studied.…”