JVI Accepts, published online ahead of print on 16 April 2008

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J. Virol. doi:10.1128/JVI.00202-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Novel post-entry resistance to AKV ecotropic mouse gammaretroviruses in the African pygmy mouse, Mus minutoides

Yuhe Yan and Christine A. Kozak^*

Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892-0460

^* To whom correspondence should be addressed. Email: ckozak{at}niaid.nih.gov.

Cells of M. minutoides, an African pygmy mouse of the subgenus Nannomys, are susceptible to ecotropic Moloney and Friend mouse leukemia viruses (MLVs), but not to AKV-type MLVs. Transfected MA139 ferret cells expressing the mCAT-1 cell surface receptor, with the minCAT-1 substitutions K222Q and V233L, did not restrict AKV MLV. Resistance of M. minutoides cells to AKV MLV was not relieved by inhibitors of glycosylation or by introduction of NIH 3T3 mCAT-1. Resistance is thus not mediated by receptor sequence variation, expression level, or glycosylation. M. minutoides cells are also infectible with lacZ pseudotypes having AKV Env and MoMLV Gag proteins further indicating that AKV Env sequence variations do not contribute to the observed block.

The pattern of virus resistance in M. minutoides differs from that of the known variants of the Fv1 post-entry resistance gene; M. minutoides is equally resistant to N-, B-, and NR-tropic AKV viruses and is equally susceptible to NR- and NB-tropic Friend MLVs. This novel resistance blocks replication before reverse transcription whereas Fv1 generally restricts replication after reverse transcription; M. minutoides cells produce 2-LTR viral DNA circles and linear viral DNA after infection with MoMLV but not with AKV MLV.

Analysis of MoMLV/AKV MLV chimeras determined that the target of resistance is in the virus capsid gene. Mutagenesis demonstrated that restriction is mediated by two amino acid substitutions, H117L and A110R; substitutions at these sites can also be targeted by the resistance genes Fv1 and TRIM5a. M. minutoides cells thus have a novel post-entry resistance to AKV MLVs.

This article has been cited by other articles:

• Yan, Y., Buckler-White, A., Wollenberg, K., Kozak, C. A. (2009). Origin, antiviral function and evidence for positive selection of the gammaretrovirus restriction gene Fv1 in the genus Mus. Proc. Natl. Acad. Sci. USA 106: 3259-3263 [Abstract] [Full Text]