5
Views
0
CrossRef citations to date
0
Altmetric
Original Article

Cyclosporin a reduces the inflammatory response to a multi-mutant herpes simplex virus type-1 leading to improved transgene expression in sympathetic preganglionic neurons in hamsters

, &
Pages 268-279 | Received 07 Jul 1998, Accepted 12 Oct 1998, Published online: 10 Jul 2009
 

Abstract

Herpes simplex virus type 1 (HSV-1) based vectors hold great promise for gene transfer to CNS neurons. Problems such as loss of transgene expression, vector-associated cytotoxicity and the immune response to the vector or encoded transgene still remain obstacles to success. We used a replication-defective, HSV-1 vector (14HΔ3vhsZ) that was engineered to have reduced cytotoxicity and express recombinant β-galactosidase. A previous study in our laboratory showed no evidence for cytotoxicity in infected neurons although an inflammatory infiltrate occurred around infected cells and transgene expression was lost between 5 and 8 days. The immune response consisted of a primary response at the site of inoculation (adrenal gland), and a secondary immune response in the spinal cord around infected adrenal sympathetic preganglionic neurons due to retrograde transport of the vector. We tested whether conventional immunosuppressants could reduce the secondary immune response, leading to improved transgene expression at the secondary CNS site. 14HΔ3vhsZ was injected into the adrenal gland in hamsters 1 day after immunosuppressant treatment began. Non-drug treated, 14HΔ3vhzZ-infected hamsters were used as controls. Cyclosporin A administration led to the most persistent /j-galactosidase activity in neurons at 5 and 8 days. Methylprednisolone treatment resulted in the greatest reduction in the inflammatory cell infiltrate but the numbers of infected neurons did not increase concomitantly. This suggested no direct relationship between extent of the inflammatory cell infiltrate and level of transgene expression. These data demonstrate the potential of cyclosporin A as an immunosuppressant adjunct treatment for HSV-1 vector-mediated gene transfer from a peripheral site to neurons in the spinal cord.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.