CD34+ Cells in the Peripheral Blood Transport Herpes Simplex Virus DNA Fragments to the Skin of Patients with Erythema Multiforme (HAEM)

• Published in: Journal of investigative dermatology Vol. 124; no. 6; pp. 1215 - 1224
• Main Authors: Ono, Fumitake, Sharma, Bhuvnesh K., Smith, Cynthia C., Burnett, Joseph W., Aurelian, Laure
• Format: Journal Article
• Language: English
• Published: Danvers, MA Elsevier Inc 01.06.2005; Nature Publishing; Elsevier Limited
• Subjects: Adult; Antigens, CD34 - metabolism; Apoptosis; Biological and medical sciences; Biological Transport; Blood Cells - metabolism; Bullous diseases of the skin; CD34+ cells; Cell Count; Cell Differentiation; Dermatology; DNA transport; DNA, Viral - metabolism; Erythema Multiforme - genetics; Erythema Multiforme - metabolism; Erythema Multiforme - physiopathology; Erythema Multiforme - virology; Genes, pol; HAEM; Herpes Simplex - complications; Herpes Simplex - metabolism; Herpes Simplex - pathology; Herpes simplex virus; HSV; Humans; langerhans cells; Langerhans Cells - pathology; Medical sciences; Simplexvirus - genetics; Skin - metabolism; Stem Cells - pathology; HAEM; DNA transport; HSV; langerhans cells; CD34+ cells; Bullous dermatosis; Human; Skin disease; HSV/HAEM/CD34 + cells/langerhans cells/DNA transport; Dermatology; Herpesviridae; Alphaherpesvirinae; Erythema multiform; Fragment; Fragmentation; Virus; Blood cell; DNA; Herpesvirus hominis; Transport
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1111/j.0022-202X.2005.23712.x

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.