Biology Faculty Articles

Document Type

Article

Publication Date

12-15-1976

Publication Title

Proceedings of the National Academy of Sciences of the United States of America

Keywords

Endogenous leukemia virus, Murine lukemia virus, Feline leukemia virus, Isozyme mapping

ISSN

1091-6490

Volume

73

Issue/No.

12

First Page

4618

Last Page

4622

Abstract

Somatic cell hybrids were constructed between BALB/c-RAG mouse cells and feline lymphoma cells by the hypoxanthine-aminopterin-thymidine selection scheme. RAG cells spontaneously produce an endogenous B-tropic type C virus. Cat-mouse hybrids preferentially segregate feline chromosomes and retain murine chromosomes,demonstrable by karyotypic and isozyme analyses. Despite the presence of the complete mouse genome, including the viral genome, virus production was diminished to 1-5% of the levels observed in RAG parents based upon particle-associated RNA-dependent DNA polymerase (reverse transcriptase) activity in the culture fluid. Thirty-seven hybrids made on four different occasions had suppressed virus levels, and no hybrids expressed parental virus levels. Reverse selection experiments on 6-thioguanine demonstrated that a restriction gene, tentatively named Bvr-1, was linked to the feline structural genes for hypoxanthine phosphoribosyltransferase (IMP:pyrophosphate phosphoribosyltransferase; EC 2.4.2.8) and glucose-6-phosphate dehydrogenase (D-glucose-6-phosphate:NADP+ 1-oxidoreductase; EC 1.1.1.49) in cats, probably on the X-chromosome. The genetic mode of action of Bvr-1 is trans dominant in restriction of murine leukemia virus. The restriction locus results in a block late in virus maturation but prior to release, since expression of antigens for viral structural proteins and mature budding particles is apparent on surfaces of restricted hybrid cells but not in high-speed pellets from culture fluid of restricted cells.

ORCID ID

0000-0001-7353-8301

ResearcherID

N-1726-2015

DOI

10.1073/pnas.73.12.4618

Peer Reviewed

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