Nature Cell Biology 3, pp 745 - 750

Scientists sometimes use pathogens for therapy. The virus responsible for herpes, Herpes Simplex Virus (HSV), can thus be attenuated by genetic engineering, and used to transfer genes to specific cells in gene therapy or in the treatment of cancer. Specificity is indeed crucial here as, in the case of cancer therapy, 'suicide' genes need to be delivered to cancer cells to trigger their self-destruction, and not to healthy cells, which must be spared. Understanding the regulation of a cell's specificity (permissiveness) to infection by HSV is thus of fundamental importance.

Patrick Lee and his colleagues at the University of Calgary, Alberta, Canada now report in the August issue of Nature Cell Biology that activation of the Ras signalling pathway increases permissiveness to HSV. They went on to investigate the molecular mechanism of regulation of HSV permissiveness by Ras, and found Ras to regulate activation of the ERK (extracellular matrix-regulated kinase) and PKR (double-stranded RNA-activated protein kinase) kinases. PKR activation is known to result in inhibition of the expression of viral protein expression, thus blocking viral replication. These findings show that HSV specifically targets cells with an activated Ras signalling pathway. The Ras pathway is constitutively activated in cells expressing oncogenes; it can also be regulated pharmacologically. This study thus paves the way to manipulations of the Ras pathway for the treatment of HSV infection, and also to optimize the use of engineered HSV in cancer therapy and gene therapy.