HHV-6 has a restricted range of susceptible species, essentially limited to humans and selected nonhuman primates. Antibodies to HHV-6 or to a closely related simian herpesvirus have been demonstrated in monkeys (Higashi et al., 1989), and a simian HHV-6 homolog has been recently identified in mandrill and drill monkeys (Lacoste et al., 2000) as well as chimpanzees (Lacoste et al., 2005). Although an established rodent model of HHV-6 infection is not presently available, preliminary experiments in human CD46-transgenic mice have shown some degree of susceptibility to HHV-6A (P. Lusso et al., unpublished). An efficient small-animal model of HHV-6 infection was developed using severe combined immunodeficiency (SCID)-hu Thy/Liv mice, in which human fetal liver and thymic tissues are implanted under the renal capsule (Gobbi et al., 1999). These mice can be successfully infected with HHV-6A and -6B, but the infection remains confined to the human graft. In vitro, HHV-6 was shown to replicate efficiently in cells from selected nonhuman primate species (Lusso et al., 1990, 1994). Experimental infection attempts in vivo have documented replication of HHV-6A (strain GS) in pig-tailed and cynomolgus macaques (P. Lusso et al., unpublished), while HHV-6B (strain HST) was found to infect cynomolgus macaques and African green monkeys (Yalcin et al., 1992).
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