TROPISM OF VARICELLA-ZOSTER VIRUS FOR HUMAN CD4(-LYMPHOCYTES AND EPIDERMAL-CELLS IN SCID-HU MICE() AND CD8(+) T)

To investigate the cell tropism and pathogenicity of varicella-zoster virus (VZV) strains, me analyzed VZV replication by using SCiD-hu mice that carry human fetal thymus/liver implants under the kidney capsule or as subcutaneous fetal skin implants, MRC-5 cells infected with wil d-type VZV or the Oka strain, used in the live attenuated varicella va ccine, were injected into the implants, The implants were surgically r emoved 2, 7, 14 and 21 days postinfection, The VZV titer from infected thymus/liver implants peaked on day 7 for the wild-type strain and on day 14 for the Oka strain, Histological analysis showed necrotic area s characterized by thymocyte depletion and fibrosis, VZV protein synth esis was detectable by immnnohistochemical staining in the necrotic ar eas and in distant regions that did not show cytopathic changes, and V ZV DNA was detected by in situ hybridization in the same distribution, Fluorescence-activated cell sorting analysis of thymocytes harvested at day 7 postinfection showed that VZV proteins were expressed in CD4( +), CD8(+), and CD4(+) CD8(+) T cells; VZV was cultured from each T-ce ll subpopulation, The Oka strain had tropism for human cell types simi lar to that of wild-type VZV, T lymphocytes released infectious VZV, w hich is a novel and important observation about the replication of thi s otherwise highly cell associated virus, VZV-infected skin implants e xhibited microscopic epidermal lesions that were indistinguishable his tologically from the characteristic lesions of varicella, These experi ments demonstrate a unique tropism of VZV for human T lymphocytes, exp laining its capacity to cause viremia in natural disease, and demonstr ate the value of the SCID-hu model for studies of VZV pathogenesis.