Varicella-zoster virus infection of human dendritic cells and transmissionto T cells: Implications for virus dissemination in the host

During primary varicella-zoster virus (VZV) infection, it is presumed that virus is transmitted from mucosal sites to regional lymph nodes, where T ce lls become infected. The cell type responsible for VZV transport from the m ucosa to the lymph nodes has not been defined. In this study, we assessed t he susceptibility of human monocyte-derived dendritic cells to infection wi th VZV, Dendritic cells were inoculated with the VZV strain Schenke and ass essed by flow cytometry for VZV and dendritic cell (CD1a) antigen expressio n. In five replicate experiments, 34.4% +/- 6.6% (mean +/- SEM) of CD1a(+) cells were also VZV antigen positive. Dendritic cells were also shown to be susceptible to VZV infection by the detection of immediate-early (IE62), e arly (ORF29), and late (gC) gene products in CD1a(+) dendritic cells, Infec tious virus was recovered from infected dendritic cells, and cell-to-cell c ontact was required for transmission of virus to permissive fibroblasts, VZ V-infected dendritic cells showed no significant decrease in cell viability or evidence of apoptosis and did not exhibit altered cell surface levels o f major histocompatibility complex (MHC) class I, MHC class II, CD86, CD40, or CD1a. Significantly, when autologous T lymphocytes were incubated with VZV-infected dendritic cells, VZV antigens were readily detected in CD3(+) T lymphocytes and infectious virus was recovered from these cells. These da ta provide the first evidence that dendritic cells are permissive to VZV an d that dendritic cell infection can lead to transmission of virus to T lymp hocytes. These findings have implications for our understanding of how viru s may be disseminated during primary VZV infection.