Abstract
The owl monkey (Aotus trivirgatus) has served as the standard non-human primate model of herpes simplex virus-1 (HSV-1) infection because it is highly susceptible to HSV-1 encephalitis. Owl monkeys, however, are expensive, difficult to obtain, and difficult to maintain in captivity, thus greatly hampering the efficiency of preclinical gene therapy trials for brain tumors using HSV-1-based vectors. We have therefore compared the susceptibility of the common marmoset (Callithrix jacchus) with the owl monkey in a model of intracerebral inoculation of wildtype HSV-1 F-strain at increasing titers. The common marmosets consistently succumbed earlier to viral encephalitis than the owl monkeys. The histological evaluation of the common marmoset revealed extensive HSV-1 infection with a concomitant yet less marked inflammatory response compared to the owl monkeys. PCR for HSV-1 demonstrated a similar extra-CNS shedding route in both experimental models. Our findings show that the common marmoset is at least as susceptible to intracerebral HSV-infection as the owl monkey and that it can therefore serve as a valid and reliable experimental model for the important preclinical safety tests of HSV-based therapeutic viral vector constructs in the brain.
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Acknowledgements
This work was supported in part by Grant CA69246 from the National Institutes of Health (to FHH, EAC, DNL) as well as by the Primate Center PHS Grant P51RR00168-40. UN is the recipient of a 2001 Toennis Scholarship of the German Society of Neurosurgery (DGNC). We thank Dr Angela Carville and Dr Paul Johnson (both New England Regional Primate Research Center, Harvard University) and Dr David Knipe (Harvard Medical School) for inspiring discussions. The valuable technical assistance of Mrs Linda Fernstein, Ms Kristen Suling, Mrs Edita Tyminski, Ms Andrea Cutone, Ms Melissa Brower, and Ms Wendy Cohen is greatly appreciated.
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Deisboeck, T., Wakimoto, H., Nestler, U. et al. Development of a novel non-human primate model for preclinical gene vector safety studies. Determining the effects of intracerebral HSV-1 inoculation in the common marmoset: a comparative study. Gene Ther 10, 1225–1233 (2003). https://doi.org/10.1038/sj.gt.3302003
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DOI: https://doi.org/10.1038/sj.gt.3302003
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