1. ¹Department of Medical Sciences, University of Calgary, Calgary, Alberta, Canada
2. ²Department of Pathology, University of Calgary, Calgary, Alberta, Canada
3. ³Department of Microbiology and Immunology, Dalhousie University, 7/F Sir Charles Tupper Building, 5850 College Street, Halifax, Nova Scotia, Canada B3H 1X5

Correspondence: Dr PWK Lee, E-mail: patrick.lee@dal.ca

Deceased March 2003

⁴Shared senior authorship

Revised 11 August 2006; Accepted 17 August 2006; Published online 3 October 2006.

Abstract

The use of oncolytic viruses has received considerable attention in recent years and many viruses have proved to be effective against a variety of cancer models and a few are currently being used in clinical trials. However, the possible emergence and outcome of virus-resistant tumour cells has not been addressed. We previously reported the effective use of reovirus against lymphoid malignancies, including the Burkitt's lymphoma cell line Raji. Here we isolated in vitro persistently infected (PI) Raji cells, and cells 'cured' of persistent reovirus infection ('cured' cells). Both PI and cured Raji cells resisted reovirus infection and cell killing in vitro. In vivo, the PI cells were non-tumorigenic in SCID mice, but cured cells regained the parental cells' ability to form tumours. Tumour xenografts from the cured cells, however, were highly susceptible to reovirus oncolysis in vivo. This susceptibility was due to the proteolytic environment within tumours that facilitates reovirus infection and cell killing. Our results show that persistent infection by reovirus impedes tumour development and that although PI cells cleared of reovirus are tumorigenic, they are killed upon rechallenge with reovirus. Both the PI and cured states are therefore not likely to be significant barriers to reovirus oncolytic therapy.