Animal Models of Human Gammaherpesvirus Infections

Humans are the only natural host of both Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV), and this strict host tropism has hampered the development of animal models of these human gammaherpesviruses. To overcome this difficulty and develop useful models for these viruses, three main approaches have been employed: first, experimental infection of laboratory animals [mainly new-world non-human primates (NHPs)] with EBV or KSHV; second, experimental infection of NHPs (mainly old-world NHPs) with EBV- or KSHV-related gammaherpesviruses inherent to respective NHPs; and third, experimental infection of humanized mice, i.e., immunodeficient mice engrafted with functional human cells or tissues (mainly human immune system components) with EBV or KSHV. These models have recapitulated diseases caused by human gammaherpesviruses, their asymptomatic persistent infections, as well as both innate and adaptive immune responses to them, facilitating the development of novel therapeutic and prophylactic measures against these viruses.