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Journal of Virology, April 2006, p. 4026-4037, Vol. 80, No. 8
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.8.4026-4037.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Novel Insights into the Pathogenesis of the Graffi Murine Leukemia Retrovirus

Véronique Voisin,1 Corinne Barat,1,{dagger} Trang Hoang,2 and Eric Rassart1*

Laboratoire de Biologie Moléculaire, Département des Sciences Biologiques, Université du Québec à Montréal, Québec, Canada,1 Institut de Recherche en Immunologie et Cancer, Université de Montréal, Québec, Canada2

Received 7 September 2005/ Accepted 25 January 2006

The Graffi murine leukemia virus (MuLV) was isolated in 1954 by Arnold Graffi, who characterized it as a myeloid leukemia-inducing retrovirus. He and his team, however, soon observed the intriguing phenomenon of hematological diversification, which corresponded to a decrease of myeloid leukemias and an increase of other types of leukemias. Recently, we derived two different molecular clones corresponding to ecotropic nondefective genomes that were named GV-1.2 and GV-1.4. The induced leukemias were classified as myeloid based on morphological analysis of blood smears. In this study, we further characterized the two variants of the Graffi murine retrovirus, GV-1.2 and GV-1.4, in three different strains of mice. We show that the Graffi MuLV is a multipotent retrovirus capable of inducing both lymphoid (T- and B-cell) and nonlymphoid (myeloid, erythroid, megakaryocytic) leukemia. Many of these are very complex with concomitant expression of different hematopoietic lineages. Interestingly, a high percentage of megakaryocytic leukemias, a type of leukemia rarely observed with MuLVs, arise in the FVB/n strain of mice. The genetic backgrounds of the different strains of mice influence greatly the results. Furthermore, the enhancer region, different for GV-1.2 and GV-1.4, plays a pivotal role in the disease specificity: GV-1.2 induces more lymphoid leukemias, and GV-1.4 induces more nonlymphoid ones.


* Corresponding author. Mailing address: Département des Sciences Biologiques, Université du Québec à Montréal, Case Postale 8888 Succ. Centre-ville, Montréal, Canada H3C-3P8. Phone: (514) 987-3000, ext. 3953. Fax: (514) 987-4647. E-mail: Rassart.Eric{at}UQAM.ca.

{dagger} Present address: Centre de Recherche en Infectiologie, Pavillon CHUL, Ste-Foy, Québec, Canada.


Journal of Virology, April 2006, p. 4026-4037, Vol. 80, No. 8
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.8.4026-4037.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.




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