Related Experiment Videos
Long terminal repeat of Friend-MCF virus contains the sequence responsible for erythroid leukemia
Abstract:
Friend-MCF virus induces erythroid leukemia when injected into newborn NFS mice whereas Moloney virus induces T-cell lymphoma. To identify the portion of Friend-MCF virus responsible for erythroid leukemia induction four in vitro recombinant viruses were constructed in which env regions or U3 regions of LTR were reciprocally exchanged between Friend-MCF and Moloney viruses. A FrMCF-Mol (LTR) virus whose genome was derived primarily from Friend-MCF virus together with 621 nucleotides of Moloney virus at its 3' end including the U3 region of LTR was a thymic lymphoma-inducing virus. A Mol-FrMCF (LTR) virus with the genome derived primarily from Moloney virus but 596 nucleotides of Friend-MCF virus information at the same region as FrMCF-Mol (LTR) was an erythroid leukemia-inducing virus. A Mol-FrMCF (env) virus whose genome was derived primarily from Moloney virus but which had 2.3 kbp of Friend MCF at the 3' end of the pol gene including most of the env gene with all of gp70 and the N terminal of p15E was a lymphoid leukemia-inducing mink cell focus-inducing virus. FrMCF-Mol (env) virus whose genome was derived primarily from Friend-MCF virus but had 2.7 kbp of Moloney virus at the same region as Mol-FrMCF (env) virus was an erythroid leukemia-inducing ecotropic virus. The Mol-FrMCF (LTR) and Mol-FrMCF (env) viruses induced mixed leukemia of erythroid and lymphoid cells in some mice.
Insights
Recombinant viruses reveal specific viral genetic regions responsible for inducing erythroid leukemia or T-cell lymphoma. The U3 region of the Long Terminal Repeat (LTR) and the env gene are key determinants of Friend-MCF virus oncogenicity.
Area of Science:
- Virology
- Oncology
- Molecular Biology
Background:
- Friend-MCF virus causes erythroid leukemia, while Moloney virus causes T-cell lymphoma in mice.
- Understanding the genetic basis of viral oncogenesis is crucial for developing targeted therapies.
Purpose of the Study:
- To pinpoint the viral genetic elements responsible for Friend-MCF virus-induced erythroid leukemia.
- To investigate the roles of the env gene and Long Terminal Repeat (LTR) U3 region in viral oncogenesis.
Main Methods:
- Construction of four in vitro recombinant viruses by exchanging env or U3 regions between Friend-MCF and Moloney viruses.
- Inoculation of newborn NFS mice with recombinant viruses to assess leukemia induction.
- Analysis of viral genome composition and resulting oncogenic potential.
Main Results:
- A recombinant virus with the Moloney U3 LTR region induced erythroid leukemia, while one with the Friend-MCF U3 LTR induced lymphoma.
- Recombinant viruses with specific env gene alterations exhibited distinct tropisms, including lymphoid leukemia induction.
- Some recombinant viruses induced mixed erythroid and lymphoid leukemia, suggesting complex interactions.
Conclusions:
- The U3 region of the LTR and the env gene are critical determinants of Friend-MCF virus's ability to induce erythroid leukemia.
- Viral genetic recombination can alter oncogenic potential and disease tropism.
- These findings contribute to understanding retroviral oncogenesis and host-pathogen interactions.