Immature Monocyte-Derived Dendritic Cells Are Productively Infected with Herpes Simplex Virus Type 1

Author:

Mikloska Zorka1,Bosnjak Lidija12,Cunningham Anthony L.1

Affiliation:

1. Centre for Virus Research, Westmead Millennium Institute and University of Sydney, Westmead,1 and

2. School of Microbiology and Immunology, University of New South Wales, Kensington,2 Australia

Abstract

ABSTRACT 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.

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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