The replicative capacity of rhesus macaque peripheral blood mononuclear cells for simian immunodeficiency virus in vitro is predictive of the rate of progression to AIDS in vivo

Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Room E1240 Biomedical Science Tower, Pittsburgh, PA 15261, USA 1 Tulane Regional Primate Research Center, 18703 Three Rivers Road, Covington, LA 70433, USA 2 Author for correspondence: Michael Murphey-Corb. Fax +1 412 648 1448. e-mail mcorb{at}pitt.edu Survival of rhesus macaques ( Macaca mulatta ) experimentally infected with simian immunodeficiency virus (SIV) varies significantly from animal to animal. Some animals die within 2 months while others survive for more than 5 years, even when identical inocula are used. This diversity in survival creates a significant problem in the design of therapeutic and vaccine trials using the SIV–macaque model because the use of small numbers of animals may provide results that are misleading. Identifying an in vitro assay that could determine the survival of monkeys prior to infection would prove extremely useful for stratifying experimental groups. Analysis of the survival of a cohort of 59 control animals obtained from over a decade of vaccine and therapeutic trials has demonstrated that the ability of peripheral blood mononuclear cells (PBMC) from a naïve animal to produce virus in vitro was highly predictive of disease progression in vivo following experimental inoculation. Animals classified in vitro as high producers of virus progressed to disease significantly more rapidly than animals classified as either low ( P =0·002) or intermediate ( P =0·013) producers of virus. The hierarchy of high and low virus production was maintained in purified CD4 + T cell cultures, indicating that this phenotype is an intrinsic property of the CD4 + T cell itself. These findings should significantly aid in the design of vaccine and therapeutic trials using the SIV–macaque model. Furthermore, since these studies suggest that the rate of virus replication is controlled by innate characteristics of the individual, they provide new insight into the pathogenesis of AIDS.