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Journal of Virology, March 2005, p. 3517-3524, Vol. 79, No. 6
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.6.3517-3524.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

B1 Lymphocytes and Myeloid Dendritic Cells in Lymphoid Organs Are Preferential Extratumoral Sites of Parvovirus Minute Virus of Mice Prototype Strain Expression

Program of Infection and Cancer, Abteilung F010 and INSERM U375,¹ Program of Functional and Structural Genomic Research, Deutsches Krebsforschungszentrum,³ Institute of Immunology, University of Heidelberg, Heidelberg, Germany,⁵ The Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, Sofia, Bulgaria,² Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD) INSERM U375, Strasbourg, France⁴

Received 5 August 2004/ Accepted 1 November 2004

Due to their oncolytic properties and apathogenicity, autonomous parvoviruses have attracted significant interest as possible anticancer agents. Recent preclinical studies provided evidence of the therapeutic potential of minute virus of mice prototype strain (MVMp) and its recombinant derivatives. In a murine model of hemangiosarcoma, positive therapeutic outcome correlated with high intratumoral expression of MVMp-encoded genes in tumors and lymphoid organs, especially in tumor-draining lymph nodes. The source and relevance of this extratumoral expression, which came as a surprise because of the known fibrotropism of MVMp, remained unclear. In the present study, we investigated (i) whether the observed expression pattern occurs in different tumor models, (ii) which cell population is targeted by the virus, and (iii) the immunological consequences of this infection. Significant MVMp gene expression was detected in lymphoid tissues from infected tumor-free as well as melanoma-, lymphoma-, and hemangiosarcoma-bearing mice. This expression was especially marked in lymph nodes draining virus-injected tumors. Fluorescent in situ hybridization analysis, multicolor fluorescence-activated cell sorting, and quantitative reverse transcription-PCR revealed that MVMp was expressed in rare subpopulations of CD11b (Mac1)-positive cells displaying CD11c⁺ (myeloid dendritic cells [MDC]) or CD45B (B220⁺ [B1 lymphocytes]) markers. Apart from the late deletion of cytotoxic memory cells (CD8⁺ CD44⁺ CD62L^–), this infection did not lead to significant alteration of the immunological profile of cells populating lymphoid organs. However, subtle changes were detected in the production of specific proinflammatory cytokines in lymph nodes from virus-treated animals. Considering the role of B1 lymphocytes and MDC in cancer and immunological surveillance, the specific ability of these cell types to sustain parvovirus-driven gene expression may be exploited in gene therapy protocols.