Friend erythroleukemia antigen. A viral antigen specified by spleen focus-forming virus and differentiation antigen controlled by the Fv-2 locus.

We have recently demonstrated that normal hemopoietic cells express RNA sequences that are homologous to sequences specific for the Friend erythroleukemia virus genome [Bernstein, A., Gamble, C., Penrose, D. & Mak, T. W. (1979) Proc. NatL Acad. Sci. USA 76,[4455][4456][4457][4458][4459]. In this communication, we report that the Fv-2 locus, the major genetic determinant controlling host susceptibility to erythroleukemia induction by Friend leukemia virus, also controls the expression of endogenous sequences related to the replication-defective component of Friend leukemia virus, Friend spleen focus-forming virus (SFFV), in normal uninfected mice. Two independent congeneic pairs of mice [C57BL/6 (B6) and B6.S; B6 and B6.C(H_7b)J, differing only in a small region of the mouse genome including the Fv-2 locus, were used for this purpose. In -both cases, molecular hybridization analysis indicated that the presence of SFFV-related RNA sequences in normal mice was associated with the Fv-2s allele: bone marrow or spleen cellular RNA from Fv-2f B6 mice contained no detectable SFFV-related sequences, whereas their congeneic Fv-2ss pairs contained relatively high levels of these RNA sequences. The absence of these RNA sequences in Fv-27 mice was not due to deletion of these sequences from the DNA of Fv-2ff mice. Repopulation of lethall irradiated Fv-2r mice with syngeneic Fv-2f' bone marrow cells did not lead to any increase in-the levels of these SFFVrelated RNA sequences, suggesting that the expression of these sequences is still reduced or inhibited in actively cycling hemopoietic cells. Infection with Friend leukemia virus resulted in the appearance of high levels of RNA homologous to SFFV-specific sequences in the leukemic spleens of B6.S (Fv-2ss) mice, whereas these cellular RNA sequences could not be detected in the spleens of Friend virus-infected B6 (Fv-2ff) mice. The demonstration that the same gene locus controls both the expression of exogenous SFFV-specific sequences and erythroleukemia induction by Friend leukemia virus suggests that these sequences may be necessary for erythroleukemic transformation. In addition, the finding that the Fv-2 gene locus controls the expression of endogenous SFFV-related sequences suggests that these sequences may also be involved in normal hemopoiesis. The genomes of a number of avian and murine sarcoma viruses contain unique sequences involved in the rapid malignant transformation of fibroblasts (1-3). These sarcoma virus-specific sequences have been found to be present in normal host cell DNA (4, 5). In addition, sequences related to the src gene of Rous sarcoma virus appear to be transcribed (6) and translated (7, 8) in normal chicken embryo fibroblasts, although a role for these sequences in normal cell function has not yet been identified. The genome of the replication-defective component of the polycythemic strain of Friend leukemia virus (FLV), Friend spleen focus-forming virus (SFFV), has also been shown to contain specific sequences (9-11). These sequences ar...

Section: Resultssupporting

confidence: 77%

“…This observation, together with the finding that the tissue distribution of both this surface antigen (22) and SFFV-related sequences (10) in normal uninfected mice follows a similar pattern, suggests that they may be related gene products.…”

Section: Resultsmentioning

confidence: 89%

Fv-2 locus controls expression of Friend spleen focus-forming virus-specific sequences in normal and infected mice

Mak

Axelrad

Bernstein

1979

“…SFFV induces an unusual disease consisting of an early (1-2 weeks) proliferation and differentiation of erythroid cells (2,8) and a late stage when transformed cells able to form tumors and permanent cell lines appear (9,10). Which of the SFFV or F-MuLV viral genomes induces the progression of transformation has not been determined, but it is known that SFFV is responsible for the early stage (8) and is under the control of the same host factors that influence normal hemopoietic development (4,(11)(12)(13). Recombinant DNA experiments have suggested that gp55, the product of the env gene, may be required for the initial cellular proliferation (14).…”

mentioning

confidence: 99%

“…As well, the premature termination and the extremely hydrophobic COOH-terminus may affect the way it is embedded in the membrane. (12) and the finding that SFFV infection extends the self-renewal capacity of hemopoietic stem cells in vivo (42). Furthermore, the major locus that controls the susceptibility of mice to Friend disease (Fv-2) controls the expression of endogenous SFFV-related sequences in hemopoietic cells (4,11) as well as the rate of proliferation of erythroid precursor cells (13).…”

mentioning

confidence: 99%

Complete nucleotide sequence of an infectious clone of Friend spleen focus-forming provirus: gp55 is an envelope fusion glycoprotein.

Clark¹,

Mak²

1983

The Friend spleen focus-forming provirus is 6,296 base pairs (bp) in length. Compared to Moloney murine leukemia virus, it has undergone five major deletions, three substitutions, and a number of minor alterations. Otherwise, these viruses are about 90% homologous. A 16-bp palindrome is found in the region thought to be involved in packaging and dimerization of the RNA genome. Premature termination of translation of the gag polyprotein is attributed to a 13-bp deletion in the p12 region. A substitution of xenotropic env sequences was identified in the 5' region of the env gene; 150 nucleotides 3' to this substitution, a deletion of 585 bp removes the site where the normal enm precursor protein is cleaved to form gp70 and p15(E), resulting in a fusion protein of Mr 44,725. Due to these changes, the env product gp55 is expected to have a substantially different conformation on the cell surface compared to either a xenotropic or ecotropic gp70 protein, and may be responsible for the rapid erythroleukemic potential of spleen focus-forming virus.Retroviruses that induce neoplasia can be classified with few exceptions into two groups: those that are slowly transforming and replication competent and those that have recombined with one of a number of cellular oncogenes to become rapidly transforming and replication defective (1). The oncogene can substitute within any of the viral structural genes: gag, which produces core proteins, poi, which encodes RNA-dependent DNA polymerase (reverse transcriptase), and env, which produces envelope glycoproteins. Each region normally produces a polyprotein that is processed by proteolytic cleavage.Friend spleen focus-forming virus (SFFV) induces a rapid erythroleukemia in mice (2, 3). However, it neither contains a cellular oncogene nor has the ability to transform fibroblasts in culture (4). It has suffered several substitutions (5, 6) and deletions (7) compared to its helper virus, Friend murine leukemia virus (F-MuLV), and is thus replication defective. SFFV induces an unusual disease consisting of an early (1-2 weeks) proliferation and differentiation of erythroid cells (2, 8) and a late stage when transformed cells able to form tumors and permanent cell lines appear (9, 10). Which of the SFFV or F-MuLV viral genomes induces the progression of transformation has not been determined, but it is known that SFFV is responsible for the early stage (8) and is under the control of the same host factors that influence normal hemopoietic development (4, 11-13). Recombinant DNA experiments have suggested that gp55, the product of the env gene, may be required for the initial cellular proliferation (14). This region contains a substitution that appears to have been derived from a xenotropic retrovirus (5-7). However, mink cell focus-forming (MCF) viruses, which are also recombinants of xenotropic env sequences, do not induce Friend disease (15,16).To establish the exact nature of the SFFV rearrangements and their relationship to pathogenicity, and also to aid in the understanding...

“…Parallel observations on the Fv-2 locus (24), a gene that has recently been found to affect proliferation of erythroid progenitor cells (25), lend support to this proposal. Dominant susceptibility alleles at the Fv-2 locus confer, on mice, sensitivity to malignant spleen focus induction by the defective genome of the Friend virus complex (24) and also specify the presence of a bone marrow alloantigen crossreactive with one induced by that defective spleen focus-forming virus genome (26). Precise definition of the relationship of Abelson antigen to Av-2, however, must await data on segregating populations and the construction of congeneic strains.…”

mentioning

confidence: 99%

Abelson antigen is expressed on hematopoietic spleen colony-forming cells from mice carrying the Av-2S virus sensitivity gene.

Risser¹

1979

Self Cite

Abelson antigen is a cell-surface determinant specifically induced by the Abelson murine leukemia virus (A-MuLV); this antigen is also expressed on uninfected bone marrow of BALB/c mice. Antisera that contained antibody to Abelson antigen were cytotoxic for the spleen colony-forming cells (CFU-S) of adult bone marrow from BALB/c mice. Absorption tests with appropriate tissues and direct cytotoxic tests with bone marrow CFU-S from several mouse strains confirmed that the sensitivity of BALB/c CFU-S to lysis by anti-Abelson-antigen antisera was due to expression of Abelson antigen. Spleen or bone marrow from BALB/c mice undergoing hematopoietic regeneration amplified Abelson antigen expression, although no expression of Abelson antigen was observed on regenerating C57BL/B6 bone marrow or spleen. The presence of Abelson antigen on bone marrow cells of seven recombinant inbred strains coincided with the inheritance of sensitivity alleles at the Av-2 locus, a gene that determines susceptibility to A-MuLV lymphoma induction. These results indicate that expression of Ableson antigen may have a physiologic function in hematopoietic differentiation and a pathologic role in A-MuLV lymphomagenesis.