Primate Models: Pros and Cons
William J. Britt
from: Cytomegaloviruses: Molecular Biology and Immunology (Edited by: Matthias J. Reddehase). Caister Academic Press, U.K. (2006)
Abstract
The pathogenesis of the human cytomegalovirus (HCMV) infection continues to be the focus of intense investigation. Although the molecular biology of this large virus has been extensively explored and a wealth of information on its structure, replication, and effects on the biology of the infected cell have been gathered, our understanding of mechanisms of disease associated with HCMV infections has lagged far behind. The most obvious explanation for the lack of a greater understanding of the pathogenesis of HCMV infections is a deficiency in suitable animal model systems that faithfully recapitulate human infection with this virus. The species specificity of CMVs has required that investigators utilize both heterologous viruses and hosts to investigate aspects of HCMV pathogenesis, thus requiring that data derived from these studies be interpreted only within the context of the specific animal model. Recent findings from studies of primate CMVs such as chimpanzee CMV (CCMV) and rhesus macaque CMV (RhCMV) have demonstrated a much closer genetic homology between these primate CMVs and HCMV than observed between HCMV and rodent or guinea pig CMVs. In fact, over 60 % of the open reading frames of RhCMV encode HCMV homologs, most with considerable predicted amino acid sequence identity. In addition, a large number of reagents are now available for the study of immunological responses of non-human primates to infection with a variety of agents, including CMVs. Finally, the development and physiology of non-human primates are reasonably well understood, at least in the context of human development and physiology. Thus, it could be argued that non-human primates, such as the rhesus macaque, offer the most informative model of the pathogenesis of HCMV infections. Importantly, findings from studies in primate models such as the macaque can be expected to be easily translated into an additional understanding of HCMV infections. Yet there are several obvious disadvantages to the use of primate models which will favor the continued use of small animal models such as the mouse and perhaps, the guinea pig. These small animal models offer distinct advantages over the primate models including; (1) lower cost, (2) availability of animals for statistically well controlled experiments, (3) capability to easily manipulate the genetic background of the experimental animal, of the mouse in particular, and (4) the ever increasing number of reagents available for use in in-vivo and in-vitro studies.. Finally, although animal experimentation generally evoke ethical concerns, this is particularly true for experimental studies that include primates. Thus, small animal models will continue to be of considerable value in the preclinical study of the pathogenesis of CMV infections and can serve to identify key aspects of CMV disease for more directed experimental studies in non-human primates as well as for the design of clinical trials read more ...
