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Journal of Virology, December 2002, p. 12112-12122, Vol. 76, No. 23
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.23.12112-12122.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Characterization of a Novel Murine Retrovirus Mixture That Facilitates Hematopoiesis

Lauren M. Hook,¹ Brooke A. Jude,¹ Victor S. Ter-Grigorov,^2,3 Janet W. Hartley,⁴ Herbert C. Morse III,⁴ Zeev Trainin,³ Vladimir Toder,² Alexander V. Chervonsky,¹ and Tatyana V. Golovkina^1*

The Jackson Laboratory, Bar Harbor, Maine 04609,¹ Department of Embryology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978,² Department of Immunology and Pathology, Kimron Veterinary Institute, Bet-Dagan 50250, Israel,³ Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892⁴

Received 15 March 2002/ Accepted 20 August 2002

A new virus previously arose in BALB/c females mated repeatedly to C57BL/6 (B6) males and then injected with fixed, activated B6 male spleen cells (V. S. Ter-Grigorov, O. Krifuks, E. Liubashevsky, A. Nyska, Z. Trainin, and V. Toder, Nat. Med. 3:37-41, 1997). In the present study, BALB/cJ mice inoculated with virus-containing plasma from affected mice developed splenomegaly, which was caused by increased numbers of Sca-1⁺ Lin^- hematopoietic stem cells (HSC) and their differentiated progeny. Biological and molecular analyses of a new virus revealed a mixture of murine leukemia viruses (MuLVs). These MuLVs comprised ecotropic and mink lung cell focus-forming (MCF) virus classes and are termed Rauscher-like MuLVs because they bear numerous similarities to the ecotropic and MCF viruses of the Rauscher MuLV complex but do not include a spleen focus-forming virus. The ecotropic virus component alone transferred some disease characteristics, while MCF virus alone did not. Thus, we have described a novel virus mixture, termed Rauscher-like MuLV, that causes an increase in hematopoiesis due to activation of pluripotent HSC. Experiments using mice and a protocol that replicated the pregnancy and immunization strategy of the original experiment demonstrated that endogenous BALB/c mouse ecotropic and xenotropic MuLVs are activated by these treatments. Emv1 was expressed in the spleens of multiparous mice but not in those of virgin mice, and Bxv1Emv1-pseudotyped MuLVs were recovered following injection of fixed, activated B6 cells. Thus, multiple pregnancies and allostimuli appear to have provided the signals required for activation of and recombination among endogenous viruses and could have resulted in generation of the Rauscher-like MuLV mixture.

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* Corresponding author. Mailing address: The Jackson Laboratory, 600 Main St., Bar Harbor, ME 04609. Phone: (207) 288-6287. Fax: (207) 288-6078. E-mail: tvg{at}aretha.jax.org.

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Journal of Virology, December 2002, p. 12112-12122, Vol. 76, No. 23
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.23.12112-12122.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

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