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Journal of Virology, August 2002, p. 8218-8224, Vol. 76, No. 16
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.16.8218-8224.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Characterization of a Polytropic Murine Leukemia Virus Proviral Sequence Associated with the Virus Resistance Gene Rmcf of DBA/2 Mice

Yong Tae Jung, Myung Soo Lyu,,{dagger} Alicia Buckler-White, and Christine A. Kozak*

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

Received 8 March 2002/ Accepted 10 May 2002

The DBA/2 mouse Rmcf gene is responsible for in vivo and in vitro resistance to infection by the polytropic mink cell focus-forming (MCF) virus subgroup of murine leukemia viruses (MLVs). Previous studies suggested that Rmcf resistance is mediated by expression of an interfering MCF MLV envelope (Env) gene. To characterize this env gene, we examined resistance in crosses between Rmcfr DBA/2 mice and Mus castaneus, a species that lacks endogenous MCF env sequences. In backcross progeny, inheritance of Rmcf resistance correlated with inheritance of a specific endogenous MCF virus env-containing 4.6-kb EcoRI fragment. This fragment was present in the DBA/2N substrain with Rmcf-mediated resistance but not in virus-susceptible DBA/2J substrain mice. This fragment contains a provirus with a 5' long terminal repeat and the 5' half of env; the gag and pol genes have been partially deleted. The Env sequence is identical to that of a highly immunogenic viral glycoprotein expressed in the DBA/2 cell line L5178Y and closely resembles the env genes of modified polytropic proviruses. The coding sequence for the full-length Rmcf Env surface subunit was amplified from DNAs from virus-resistant backcross mice and was cloned into an expression vector. NIH 3T3 and BALB 3T3 cells stably transfected with this construct showed significant resistance to infection by MCF MLV but not by amphotropic MLV. This study identifies an Rmcf-linked MCF provirus and indicates that, like the ecotropic virus resistance gene Fv4, Rmcf may mediate resistance through an interference mechanism.

* Corresponding author. Mailing address: NIH, NIAID, LMM, Bldg. 4, Room 329, 4 Center Dr., MSC 0460, Bethesda, MD 20892-0460. Phone: (301) 496-0972. Fax: (301) 480-2808. E-mail: ckozak{at}nih.gov.

{dagger} Present address: Laboratory of Population Genetics, National Cancer Institute, Bethesda, MD 20892.

Journal of Virology, August 2002, p. 8218-8224, Vol. 76, No. 16
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.16.8218-8224.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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