Genetic Analysis of the Rat Leukemia Virus: Influence of Viral Sequences in Transduction of the c-rasProto-Oncogene and Expression of Its Transforming Activity

ABSTRACT The rat leukemia virus (RaLV) is an endogenous retrovirus that is spontaneously released by Sprague-Dawley rat embryo cells. The overall structure of the RaLV genome resembles that of other simple, replication-competent retroviruses, but the sequence of the long terminal repeats (LTR) is unique and unrelated to the known retroviruses. Phylogenetically, the RaLV genome appears to be more closely related to the feline leukemia virus group of retroviruses than to the murine leukemia virus group. A remarkable feature of RaLV is that it is capable of transducing a ras proto-oncogene from rat tumor cells in the form of an acutely transforming virus, designated the Rasheed strain of the rat sarcoma virus (RaSV). With the exception of the c-ras sequence, the genomes of both RaLV and RaSV are collinear. The RaSV-encoded oncogene v-Ra-rasexpresses a fusion protein with a molecular mass of 29 kDa, and it exhibits a unique structure that has not been described previously for any known virus. The 5′ end of this gene is derived from sequences encoding RaLV matrix followed by 20 bp derived from the U5 region of the RaLV LTR (RS-U5 element) which is joined at its 3′ end to sequences derived from all six (coding and noncoding) exons of the c-ras proto-oncogene at the 3′ end. This recombinational event represents a novel mechanism among the acutely transforming viruses that have been studied.

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A Report Of Morphologically Aberrant Virus Particles in Cells Infected With MSV (FelLV) Virus

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100073362 ◽

1973 ◽

Vol 31 ◽

pp. 584-585

Author(s):

R. A. Al-Adhami ◽

A. L. Chapman

Keyword(s):

Leukemia Virus ◽

Feline Leukemia Virus ◽

Virus Particles ◽

Induced Tumors ◽

Embryo Cells ◽

Murine Sarcoma Virus ◽

Sarcoma Virus ◽

Mouse Cells ◽

Type C ◽

Murine Sarcoma

Fujinaga et al reported MSV induced rat and hamster osteosarcoma which showed an occassional unusual bud in the rat induced tumors. Savage and Hackett and Hackett and Sylvester reported abnormal type C virus in UCLB cells derived from Balb/3t3 cells infected and transformed with MLV. They wer unable to demonstrate sarcoma virus activity. Fischinger and O‘Connor reported the infection of cat embryo cells by a centrifugally induced aggregate of murine sarcoma virus and feline leukemia virus designated as MSV(FelLV). This virus gave rise to a defective, focus forming virus which propagated in cat cells but not in mouse cells.In the present study the morphoiogy of the MSV(FelLV) virus obtained from Dr. Fischinger and maintained in our laboratory since 1970 will be reported. Feline embryo fibroblasts (established in our lab.) and Crandall feline kidney cells (Cutter-Haver-Lockhart, Shawnee, Kansas) were used in this study.

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A p60 polypeptide in the feline leukemia virus pseudotype of Moloney sarcoma virus with murine leukemia virus p30 antigenic determinants.

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.72.6.2380 ◽

1975 ◽

Vol 72 (6) ◽

pp. 2380-2384 ◽

Cited By ~ 11

Author(s):

M. K. Oskarsson ◽

W. G. Robey ◽

C. L. Harris ◽

P. J. Fischinger ◽

D. K. Haapala ◽

...

Keyword(s):

Murine Leukemia Virus ◽

Leukemia Virus ◽

Feline Leukemia Virus ◽

Antigenic Determinants ◽

Sarcoma Virus ◽

Moloney Sarcoma Virus ◽

Murine Leukemia

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Trans-Species Rescue of Defective Genomes of Murine Sarcoma Virus from Hamster Tumor Cells with Helper Feline Leukemia Virus

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.65.1.81 ◽

1970 ◽

Vol 65 (1) ◽

pp. 81-87 ◽

Cited By ~ 18

Author(s):

P. S. Sarma ◽

T. Log ◽

R. J. Huebner

Keyword(s):

Tumor Cells ◽

Leukemia Virus ◽

Feline Leukemia Virus ◽

Murine Sarcoma Virus ◽

Sarcoma Virus ◽

Murine Sarcoma

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Erratum: Trans-Species Rescue of Defective Genomes of Murine Sarcoma Virus from Hamster Tumor Cells with Helper Feline Leukemia Virus

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.66.2.583 ◽

1970 ◽

Vol 66 (2) ◽

pp. 583-583

Keyword(s):

Tumor Cells ◽

Leukemia Virus ◽

Feline Leukemia Virus ◽

Murine Sarcoma Virus ◽

Sarcoma Virus ◽

Murine Sarcoma

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Structural diversity and nuclear protein binding sites in the long terminal repeats of feline leukemia virus.

Journal of Virology ◽

10.1128/jvi.64.4.1675-1682.1990 ◽

1990 ◽

Vol 64 (4) ◽

pp. 1675-1682 ◽

Cited By ~ 36

Author(s):

R Fulton ◽

M Plumb ◽

L Shield ◽

J C Neil

Keyword(s):

Protein Binding ◽

Binding Sites ◽

Nuclear Protein ◽

Leukemia Virus ◽

Structural Diversity ◽

Feline Leukemia Virus ◽

Long Terminal Repeats ◽

Protein Binding Sites ◽

Terminal Repeats

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An Immunoelectron Microscopic Study of Type C Virus Particles in Feline Sarcoma Virus-Induced Rat Tumors

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100051244 ◽

1974 ◽

Vol 32 ◽

pp. 246-247

Author(s):

K. Maruyama ◽

M. F. Miller ◽

S. H. Wagner ◽

L. Dmochowski

Keyword(s):

Leukemia Virus ◽

Feline Leukemia Virus ◽

Virus Particles ◽

Tumor Viruses ◽

Induced Tumors ◽

Sarcoma Virus ◽

Type C ◽

Rat Tumors ◽

Rna Tumor Viruses ◽

Host Influence

Many type C RNA tumor viruses can infect cells of different species. Following cross-species infection, these viruses are known to exhibit some altered properties. In an attempt to investigate host influence on properties of mammalian RNA tumor viruses, neonatal Wistar rats were inoculated with feline sarcoma virus of Snyder-Theilen strain. A transplantable tumor line designated as RT-FeSV was established from one of these induced tumors. Some syngeneic rats inoculated with RT-FeSV tumors which were passaged in rats less than 3 times developed precipitable serum antibodies to feline leukemia virus (FeLV).

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In vitro methylation of specific regions of the cloned Moloney sarcoma virus genome inhibits its transforming activity

Molecular and Cellular Biology ◽

10.1128/mcb.3.3.305-314.1983 ◽

1983 ◽

Vol 3 (3) ◽

pp. 305-314

Author(s):

M L McGeady ◽

C Jhappan ◽

R Ascione ◽

G F Vande Woude

Keyword(s):

Leukemia Virus ◽

Specific Inhibitor ◽

Virus Genome ◽

Moloney Murine Leukemia Virus ◽

Methyl Groups ◽

Proviral Dna ◽

Sarcoma Virus ◽

Transforming Activity ◽

Moloney Sarcoma Virus

The transforming activity of cloned Moloney sarcoma virus (MSV) proviral DNA was inhibited by in vitro methylation of the DNA at cytosine residues, using HpaII and HhaI methylases before transfection into NIH 3T3 cells. The inhibition of transforming activity due to HpaII methylation was reversed by treatment of the transfected cells with 5-azacytidine, a specific inhibitor of methylation. Analysis of the genomic DNA from the transformed cells which resulted from the transfection of methylated MSV DNA revealed that the integrated MSV proviral DNA was sensitive to HpaII digestion in all cell lines examined, suggesting that loss of methyl groups was necessary for transformation. When cells were infected with Moloney murine leukemia virus at various times after transfection with methylated MSV DNA, the amount of transforming virus produced indicated that the loss of methyl groups occurred within 24 h. Methylation of MSV DNA at HhaI sites was as inhibitory to transforming activity as methylation at HpaII sites. In addition, methylation at both HpaII and HhaI sites did not further reduce the transforming activity of the DNA. These results suggested that; whereas methylation of specific sites on the provirus may not be essential for inhibiting the transforming activity of MSV DNA, methylation of specific regions may be necessary. Thus, by cotransfection of plasmids containing only specific regions of the MSV provirus, it was determined that methylation of the v-mos gene was more inhibitory to transformation than methylation of the viral long terminal repeat.

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