Herpesvirus infections of laboratory macaques

Non-human primates (NHPs), primarily macaques, are commonly used as non-rodent species in pre-clinical safety assessment studies. The use of macaques in such studies is increasing largely due to the development of biopharmaceutical and immunomodulatory therapies that necessitates extensive safety testing. Macaques, commonly available for use in such studies, are infected by a rich flora of herpesviruses that cause persistent, latent, life-long infections. Primary infection of immune competent macaques is typically subclinical with very little associated morbidity and mortality only in very rare cases. A life-long consequence of herpesvirus infection is periodic stochastic and frequently asymptomatic recurrences from latency throughout an infected macaque's lifetime. With immune modulation or suppression, however, immune control of herpesvirus infections can be lost, resulting in significant disease and even death of the affected animals. Since macaques undergo primary infection with herpesviruses starting around 4-6 months-of-age when maternally-derived antibody begins to wane, it is difficult and costly to derive animals that are herpesvirus-free. Further, the herpesvirus flora and prevalence of infection in laboratory macaques mirrors that of the adult human population making the herpesvirus-infected macaque a reasonable model of the general human population. This review is intended to familiarize toxicologists performing preclinical drug safety studies with the basic biology, disease pathogenesis and consequences of immune suppression in herpesvirus-infected laboratory macaques.