Retroviruses prefer transcriptional units

The integration pattern of MLV vehicles has important implications for gene therapy | By Tudor Toma

Retroviral integration was assumed to be a random process, and consequently, retroviruses have been considered safe gene delivery vehicles for use in gene therapy. However, recent reports of leukemia in two of 11 children treated for a rare blood disease with a murine leukemia virus (MLV) –based gene therapy vector questioned the random nature of retroviral integration. In the June 13 Science, Xiaolin Wu and colleagues at the National Institutes of Health show that transcription start regions in the human genome are favored targets for MLV integration (Science, 300:1749-1751, June 13, 2003).

Wu et al. mapped 903 MLV and 379 human immunodeficiency virus–1 (HIV-1) integrations in the human genome. They observed that MLV preferred integration near the start of transcriptional units, either upstream or downstream. However, HIV-1 preferred integration anywhere in the transcriptional unit but not upstream of the transcriptional start.

"That both viruses favor expressed genes is consistent with preferential integration into opened chromatin. However, their preference for distinct regions within genes suggests that active tethering rather than passive diffusion is at play, governed by virus-specific, preintegration complex (PIC) associated determinants," writes Didier Trono from the University of Geneva in an associated editorial.