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Journal of Virology, June 2008, p. 5307-5315, Vol. 82, No. 11
0022-538X/08/$08.00+0     doi:10.1128/JVI.00089-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Mutations Affecting the MA Portion of the v-Abl Protein Reveal a Conserved Role of Gag in Abelson Murine Leukemia Virus (MLV) and Moloney MLV

Chae-ryun Yi^1,2, and Naomi Rosenberg^1,2,3*

Molecular Microbiology Graduate Program, Sackler School of Graduate Biomedical Sciences,¹ Departments of Molecular Biology and Microbiology,² Pathology, Tufts University School of Medicine, Boston, Massachusetts 02111³

Received 14 January 2008/ Accepted 15 March 2008

Abelson murine leukemia virus (Ab-MLV) arose from a recombination between gag sequences in Moloney MLV (Mo-MLV) and the c-abl proto-oncogene. The v-Abl oncoprotein encoded by Ab-MLV contains MA, p12, and a portion of CA sequences derived from the gag gene of Mo-MLV. Previous studies indicated that alteration of MA sequences affects the biology of Mo-MLV and Ab-MLV. To understand the role of these sequences in Ab-MLV transformation more fully, alanine substitution mutants that affect Mo-MLV replication were examined in the context of Ab-MLV. Mutations affecting Mo-MLV replication decreased transformation, while alanine mutations in residues dispensable for Mo-MLV replication did not. The altered v-Abl proteins displayed aberrant subcellular localization that correlated to transformation defects. Immunofluorescent analyses suggested that aberrant trafficking of the altered proteins and improper interaction with components of the cytoskeleton were involved in the phenotype. Similar defects in localization were observed when the Gag moiety containing these mutations was expressed in the absence of abl-derived sequences. These results indicate that MA sequences within the Gag moiety of the v-Abl protein contribute to proper localization by playing a dominant role in trafficking of the v-Abl molecule.

Published ahead of print on 26 March 2008.

Present address: Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital/Harvard Medical School, Cambridge, MA 02139.