Journal of Leukocyte Biology Myeloid cells, immune suppression, tumor immunology
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Originally published online as doi:10.1189/jlb.0306151 on August 21, 2006

Published online before print August 21, 2006
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(Journal of Leukocyte Biology. 2006;80:1013-1017.)
© 2006 by Society for Leukocyte Biology

Retroviral E-DNA: persistence and gene expression in nondividing immune cells

Andrea Cara* and Mary E. Klotman{dagger},1

* Department of Drug Research and Evaluation, Istituto Superiore di Sanità, Rome, Italy; and
{dagger} Division of Infectious Disease, Department of Medicine, Mount Sinai School of Medicine, New York, New York, USA

1 Correspondence: Mt. Sinai School of Medicine, Box 1090, 1 Gustave L. Levy Place, New York, NY 10029, USA. E-mail: mary.klotman{at}mssm.edu

Following retroviral infection of cells, not only is the proviral DNA integrated into the host genome, but there is also an accumulation of unintegrated extrachromosomal DNA (E-DNA), both linear and circular. Although the integrated DNA is responsible for the production of viral proteins and new viral progeny, the role of E-DNA has remained uncertain. Several reports have shown that E-DNA is transcriptionally active producing both RNA, as well as viral proteins and that circular E-DNA can persist in nondividing cells, raising questions regarding the potential consequences of this reservoir. Furthermore, integrase inhibitors, presently in clinical trials, shifts the balance of proviral DNA to the E-DNA form. This review is focused on recent work in this field with an emphasis on exploring the potential role of E-DNA in both pathogenesis of retroviral infections, especially HIV-1, and as a tool to deliver and express genes.

Key Words: unintegrated DNA • HIV-1 • integrase inhibitors • vaccine • gene therapy




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