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Journal of Virology, July 2001, p. 5958-5964, Vol. 75, No. 13
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.13.5958-5964.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Immature Monocyte-Derived Dendritic Cells Are
Productively Infected with Herpes Simplex Virus Type 1
Zorka
Mikloska,1,*
Lidija
Bosnjak,1,2 and
Anthony L.
Cunningham1
Centre for Virus Research, Westmead
Millennium Institute and University of Sydney,
Westmead,1 and School of Microbiology
and Immunology, University of New South Wales,
Kensington,2 Australia
Received 27 December 2000/Accepted 3 April 2001
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.
*
Corresponding author. Mailing address: Centre for Virus
Research, Westmead Millennium Institute, P.O. Box 412, Westmead, NSW 2145, Australia. Phone: 61-2-9845-9115. Fax: 61-2-9845-9100. E-mail: zorka_mikloska{at}wmi.usyd.edu.au.
Journal of Virology, July 2001, p. 5958-5964, Vol. 75, No. 13
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.13.5958-5964.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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