Immature monocyte-derived dendritic cells are productively infected with herpes simplex virus type 1.
Herpes simplex viruses (HSV) have developed several immunoevasive strategies. 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 show productive infection of immature monocyte-derived DC, which closely resemble sessile Langerhans cells, by sequential expression of immediate-early, early, and late viral proteins and of glycoprotein D mRNA, as well as production of infectious virus of moderate titers. Infection was cytopathic, with the progressive loss of 20 to 45% of cells from 24 to 48 h after infection, 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 infection of monocytes and mature monocyte-derived DC. Infection of immature DC also led to selective and asynchronous downregulation of CD1a, CD40, CD54 (ICAM-1) (12 h postinfection), CD80 (24 h postinfection), and CD86 (48 h postinfection) 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 may lead to delayed activation of T cells, allowing more time for replication of HSV type 1 in epidermal cells.
Mikloska
Z
Z
Centre for Virus Research, Westmead Millennium Institute and University of Sydney, Westmead, NSW 2145, Australia. zorka_mikloska@wmi.usyd.edu.au
Bosnjak
L
L
Cunningham
A L
AL
D018949:Antigens, CD1 / Q000096:biosynthesis; D000956:Antigens, Viral / Q000032:analysis; D003713:Dendritic Cells / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000276:immunology / Q000502:physiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D009000:Monocytes / Q000821:virology*; D014779:Virus Replication
D018949:Antigens, CD1; D000956:Antigens, Viral; C419393:CD1a antigen; D018799:Intercellular Adhesion Molecule-1