1. ^*Department of Pharmacology and Experimental Therapeutics, The University of Maryland School of Medicine, Baltimore, Maryland, USA
2. ^†Department of Dermatology, The University of Maryland School of Medicine, Baltimore, Maryland, USA

Correspondence: Dr Laure Aurelian, Virology/Immunology Laboratories, University of Maryland, Bressler, Room 4-023, 655 West Baltimore Street, Baltimore, Maryland 21201, USA. Email: laurelia@umabnet.ab.umd.edu

¹Present address: Department of Dermatology, Kurume University Medical School, Kurume, Japan.

Received 24 August 2004; Revised 7 January 2005; Accepted 12 January 2005; Published online 3 June 2005.

Abstract

Herpes simplex virus (HSV)-associated erythema multiforme (HAEM) is a recurrent disease characterized by the presence and expression of HSV DNA fragments in lesional skin. Our studies examined the mechanism of viral DNA transport to the skin of HAEM patients. CD34+ cells were isolated from the blood of normal subjects and HSV and HAEM patients during acute lesions and at quiescence. They were cultured with cytokines that favor their differentiation into Langerhans cells (LC) precursors (CD1a+/CD14-) and examined for HSV replication, HSV-induced cellular alterations, viral DNA fragmentation, and clearance. CD34+ cells from all study groups were non-permissive for HSV replication but infection favored their differentiation into CD1a+/CD14- LC precursors and upregulated E-cadherin expression, thereby assisting LC targeting to the skin. Only HAEM patients had CD34+ cells that retained viral DNA fragments, notably polymerase DNA, for at least 7 d of in vitro culture. The percentages of circulating CD34+ (and CD34+/CLA+) cells were significantly higher in HAEM patients at the time of acute lesions. A similar increase was not seen for HSV patients. The data are the first report implicating CD34+ cells in HAEM pathogenesis, likely by transporting HSV DNA fragments to lesional skin.