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Molecular cloning of a highly leukemogenic, ecotropic retrovirus from an AKR mouse
Abstract:
SL3-3 is a leukemogenic, ecotropic retrovirus produced by a T-cell line derived from a spontaneous lymphoma of an AKR mouse. We have isolated a molecular clone of its DNA provirus from infected NIH 3T3 fibroblasts. Cloned proviral DNA produced infectious virus upon transfection onto NIH 3T3 cells. Virus derived by transfection induced lymphomas at high frequency in AKR/J, C3H(f)/Bi, CBA/J, and NFS/N mice. Heteroduplex and RNase T1 fingerprinting analyses showed that the genomes of SL3-3 and the non-leukemogenic virus, Akv, contain no major substitutions relative to one another and differ by only a few base changes. These results unambiguously show that SL3-3 is a highly leukemogenic virus and that major rearrangements of the genome relative to Akv are not required for virulence.
Insights
SL3-3 is a highly leukemogenic retrovirus that causes lymphomas in mice. Minor genetic differences, not major rearrangements, between SL3-3 and non-leukemogenic Akv virus explain its virulence.
Area of Science:
- Virology
- Oncology
- Molecular Biology
Background:
- SL3-3 is an ecotropic retrovirus associated with T-cell lymphomas in AKR mice.
- Understanding the genetic basis of retroviral leukemogenesis is crucial for developing targeted therapies.
Purpose of the Study:
- To molecularly clone and characterize the SL3-3 retrovirus.
- To determine the genetic factors responsible for SL3-3's high leukemogenic potential.
Main Methods:
- Molecular cloning of SL3-3 proviral DNA from infected NIH 3T3 fibroblasts.
- Transfection of cloned DNA to produce infectious virus.
- Viral induction of lymphomas in susceptible mouse strains (AKR/J, C3H(f)/Bi, CBA/J, NFS/N).
- Comparative genomic analysis using heteroduplex and RNase T1 fingerprinting.
Main Results:
- Infectious SL3-3 virus was successfully produced from a molecular clone.
- Transfected SL3-3 induced lymphomas with high frequency across multiple mouse strains.
- Genomic comparison revealed minimal differences between SL3-3 and the non-leukemogenic Akv virus, with only a few base changes identified.
Conclusions:
- SL3-3 is unequivocally a highly leukemogenic retrovirus.
- Major genomic rearrangements are not necessary for SL3-3's virulence; minor genetic alterations are sufficient.
- These findings provide critical insights into retroviral oncogenesis and host susceptibility.