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The TP1 isolate of feline sarcoma virus encodes a fgr-related oncogene lacking gamma actin sequences
B Kappes1, A Ziemiecki, R G Müller
1Institut für Medizinische Virologie, Justus-Liebig-Universität, Giessen, Federal Republic of Germany.
Abstract:
We have isolated a new feline sarcoma virus, TP1-FeSV. The virus encodes a myristilated 83 kD gag-onc fusion protein displaying tyrosine kinase activity. We have established nonproducer cell lines lacking the TP1-FeSV associated helper virus (FeLV) and TP1-FeSV transfected NIH cell lines. Southern Blot analysis of genomic DNA and Northern Blot analysis of RNA isolated from these cell lines revealed that the oncogene of the TP1-FeSV isolate is related to the fgr oncogene of the GR-FeSV, but shows no hybridization to the gamma actin homologous sequences of the GR-FeSV. We have isolated TP1-FeSV specific clones from a genomic library. Restriction enzyme and sequence analysis showed that the TP1-FeSV genome consists of the first 1651 nucleotides of the gag gene, followed directly by fgr sequences. The TP1-FeSV fgr sequence starts 43 nucleotides after the beginning of the GR-FeSV fgr sequence. In contrast to the GR-FeSV fgr which has lost 13 amino acids of the c-fgr carboxy terminus, the TP1-FeSV fgr contains the complete carboxy terminus of the cellular fgr gene. The TP1-FeSV fgr sequence is followed by a unique 328 nucleotide long sequence of unknown origin. The 3' recombination site occurs within the pol gene, 460 nucleotides from the start of the env leader sequence. Comparison of the subcellular localization of the transforming proteins of TP1-FeSV and GR-FeSV show no striking difference; both molecules are in part associated with subcellular membrane/cytoskeletal fractions and form complexes with the cellular pp90 and pp50.
Insights
A new feline sarcoma virus, TP1-FeSV, was identified, encoding a gag-onc fusion protein with tyrosine kinase activity. Its oncogene is related to fgr, differing from GR-FeSV by retaining the complete carboxy terminus.
Area of Science:
- Virology
- Oncology
- Molecular Biology
Background:
- Feline sarcoma viruses (FeSVs) are retroviruses known to cause tumors in cats.
- Oncogenes within these viruses play a critical role in tumorigenesis.
- Understanding the genetic makeup and oncogenic potential of novel FeSVs is crucial for cancer research.
Purpose of the Study:
- To isolate and characterize a new feline sarcoma virus, TP1-FeSV.
- To determine the genetic structure and oncogenic properties of TP1-FeSV.
- To compare TP1-FeSV with other known FeSVs, such as GR-FeSV.
Main Methods:
- Isolation and characterization of TP1-FeSV.
- Establishment of nonproducer and transfected cell lines.
- Southern Blot and Northern Blot analyses for genomic and RNA analysis.
- Genomic library screening, restriction enzyme digestion, and sequence analysis.
- Subcellular localization studies of viral proteins.
Main Results:
- TP1-FeSV encodes an 83 kD gag-onc fusion protein with tyrosine kinase activity.
- The TP1-FeSV oncogene is related to the fgr oncogene but distinct from GR-FeSV.
- TP1-FeSV retains the complete carboxy terminus of the cellular fgr gene, unlike GR-FeSV.
- A unique 328 nucleotide sequence of unknown origin follows the fgr sequence in TP1-FeSV.
- TP1-FeSV and GR-FeSV transforming proteins show similar subcellular localization and complex formation.
Conclusions:
- TP1-FeSV represents a novel feline sarcoma virus with unique genetic characteristics.
- The fgr oncogene in TP1-FeSV is structurally distinct from that in GR-FeSV, particularly regarding its carboxy terminus.
- The findings contribute to understanding the diversity and evolution of feline sarcoma viruses and their oncogenic mechanisms.