Disease relevance of Spleen Focus-Forming Viruses

• The retroviral integration site Fli-1 is rearranged in 75% of the erythroleukemia cell clones induced by Friend murine leukemia virus (F-MuLV), whereas Spi-1/PU.1, a member of the ets family of DNA-binding proteins, is rearranged in 95% of the erythroleukemias induced by Friend spleen focus-forming virus (SFFV) [1].
• Friend erythroleukemia antigen. A viral antigen specified by spleen focus-forming virus and differentiation antigen controlled by the Fv-2 locus [2].
• Two recombinant retroviruses expressing EpoR(R129C), spleen focus-forming virus (SFFVc-EpoR) and myeloproliferative sarcoma virus (MPSVcEpoR), were used to infect fetal liver cells that served as a source of hematopoietic progenitors [3].
• In addition, we have found that leukemia cells from mice infected with the erythroleukemic Rauscher virus complex contain a membrane glycoprotein that appears similar to the gp55 encoded by Friend spleen focus-forming virus [4].
• Furthermore, the replication-defective Friend spleen focus-forming virus (F-SFFV) encodes a membrane glycoprotein with an apparent Mr of 55,000 (designated gp55), which is structurally and immunologically related to the membrane envelope glycoproteins of dual tropic murine leukemia viruses [5].

High impact information on Spleen Focus-Forming Viruses

• These alterations in metabolism and tumorigenicity caused by the EPOR with activating point mutations are similar to those observed in erythropoietin-independent activation of the wild type EPOR by association with gp55, the Friend spleen focus-forming virus glycoprotein [6].
• Activation of cell growth by binding of Friend spleen focus-forming virus gp55 glycoprotein to the erythropoietin receptor [7].
• DNA from a replication-defective spleen focus-forming virus (SFFV) was reconstructed and transfected into psi-2 cells containing a packaging-defective mutant of Moloney murine leukemia virus [8].
• Spleen cells taken from mice infected as adults with two different variants of the spleen focus-forming virus (SFFV), SFFVP and SFFVA, as well as spleen cells taken from mice infected as newborns with Friend murine leukemia virus (F-MuLV) were assayed in a proliferation assay in the presence or absence of the erythroid hormone erythropoietin (Epo) [9].
• Env-derived gp55 gene of Friend spleen focus-forming virus specifically induces neoplastic proliferation of erythroid progenitor cells [10].

Chemical compound and disease context of Spleen Focus-Forming Viruses

• Induction of endogenous and of spleen focus-forming viruses during dimethylsulfoxide-induced differentiation of mouse erythroleukemia cells transformed by spleen focus-forming virus [11].
• In particular, the decrease in STF and SSRFC levels is ascribed to the replication-competent (Friend-murine leukemia virus) component of Friend leukemia virus complex, whereas the decrease in AZ sensitivity of splenocytes and the increase of SSRFCs are ascribed to the defective spleen focus-forming virus component of the complex [12].
• The EPOR can be activated, resulting in proliferation independent of EPO either by an Arg129 to Cys point mutation or by association with the Friend spleen focus-forming virus (SFFV) envelope glycoprotein gp55 [13].
• Ex vivo and in vivo biological effects of a truncated form of the receptor tyrosine kinase stk when activated by interaction with the friend spleen focus-forming virus envelope glycoprotein or by point mutation [14].
• Dimethyl sulfoxide affects the amount of extrachromosomal spleen focus-forming virus DNA in murine erythroleukemia cells [15].

Biological context of Spleen Focus-Forming Viruses

• Molecular cloning of F5-5-derived cDNA encoding EPOR revealed that the 5' noncoding region of the EPOR cDNA corresponds to the 3' long terminal repeat sequence of the polycythemic strain of Friend spleen focus-forming virus (F-SFFVP) [16].
• Further, no nucleotide sequences were found that were homologous to the Friend spleen focus-forming virus glycoprotein gp55, which has been shown to bind to and activate the murine EPO-receptor [17].
• We have shown previously that spleen focus forming virus integration near the Spi-1 putative oncogene is observed in 95% of erythroid Friend tumors (Moreau-Gachelin et al., 1988) [18].
• To determine the biological significance of the 585-base-pair deletion in the env gene of Friend spleen focus-forming virus (SFFV) encoding a leukemogenic glycoprotein (gp55), we examined the pathogenicity of a constructed mutant SFFV (SFFVDF) [19].
• All of the 2-kb transcripts contained sequences homologous to the xenotropic virus-related env sequences in the Friend spleen focus-forming virus, representing the N-terminal portion of gp70 [20].

Anatomical context of Spleen Focus-Forming Viruses

• The number of erythroid colonies produced after 2 days of culture without erythropoietin or fetal calf serum was approximately proportional to the titer of Friend spleen focus-forming virus to whcih the bone marrow cells had been exposed [21].
• Fusion of the erythropoietin receptor and the Friend spleen focus-forming virus gp55 glycoprotein transforms a factor-dependent hematopoietic cell line [22].
• Using a DNA probe prepared from cloned env gene sequences of Friend spleen focus-forming viruses, we detected the differential expression of multiple RNA species in uninfected DBA/2 fibroblasts and in various tissues from adult DBA/2 and NZB mice [23].
• The leukemogenic glycoprotein (gp55) encoded by Friend spleen focus-forming virus is predominantly retained in the rough endoplasmic reticulum (RER) [24].
• Infection of erythroid cells with the Friend spleen focus-forming virus (SFFV) leads to the interaction of the viral envelope glycoprotein with the Epo receptor and renders these cells Epo independent [25].

Gene context of Spleen Focus-Forming Viruses

• A frequent event in the generation of these malignant cells is deregulation of the hematopoietic-specific transcription factor PU.1 (Spi-1) by retroviral insertion of the spleen-focus-forming virus component of Friend virus [26].
• The nonresponsiveness to Epo presumably results from gp55, the product of the env gene encoded by the Friend spleen focus-forming virus (F-SFFV), acting as a pseudoligand and constitutively activating the receptor [27].
• The positions of a 585-base deletion, a 6-base duplication, and a point insertion that leads to a frame shift and premature protein termination in the ecotropic 3' end of env were invariant between three spleen focus-forming virus strains, indicating that they had a single common ancestor [28].
• The FMEV-type vector SF/Lyt contained the spleen focus-forming virus U3 and the MESV primer-binding site (PBS), while MO3/Lyt contained the U3 region and PBS from Mo-MuLV [29].
• IL-7 significantly prolonged survival time and decreased spleen focus-forming virus (SFFV) levels, expression of SFFV mRNA and SFFV protein production in FVC-infected mice [30].

Analytical, diagnostic and therapeutic context of Spleen Focus-Forming Viruses

• In an animal model of a murine retroviral disease, KH164 was shown to inhibit in a dose-dependent manner the progression of the disease induced by Friend virus complex (a mixture of Friend MLV and spleen focus-forming virus) [31].

References