Immature monocyte-derived dendritic cells are productively infected with herpes simplex virus type 1

Herpes simplex viruses (HSV) have developed several immunoevasive strategie s. Here we demonstrate a novel mechanism by which HSV type 1 may interfere with the immune response through infection of immature dendritic cells (DC) and selective downmodulation of costimulatory molecules. In our study we s how productive infection of immature monocyte-derived DC, which closely res emble sessile Langerhans cells, by sequential expression of immediate-early , early, and late viral proteins and of glycoprotein D mRNA, as well as pro duction of infectious virus of moderate titers. Infection was cytopathic, w ith the progressive loss of 20 to 45% of cells from 24 to 48 h after infect ion, with no more than 80% of DC found to be infected. These results are in contrast to those of previous findings of nonpermissive or abortive infect ion of monocytes and mature monocyte-derived DC. Infection of immature DC a lso led to selective and asynchronous downregulation of CD1a, CD40, CD54 (I CAM-1) (12 h postinfection), CD80 (24 h postinfection), and CD86 (48 h post infection) but not of CD11c or major histocompatibility complex class I and II molecules when compared to DC exposed to UV-inactivated virus. Thus, we propose that productive infection of epidermal Langerhans cells in vivo ma y lead to delayed activation of T cells, allowing more time for replication of HSV type 1 in epidermal cells.