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An increase in disease latency is associated with a host-dependent selection for recombinant murine leukemia viruses
C Y Thomas1, M A Coppola, J D Nuckols
1Department of Internal Medicine, University of Virginia Health Sciences Center, Charlottesville 22908.
Abstract:
The genomes of recombinant murine leukemia viruses recovered from HRS/J (type I env recombinants) and CWD (type II env recombinants) mice have distinct envelope gene structures. To better understand the biologic significance of these differences, we examined the differences in the responses of HRS/J and CWD mice to inoculation with an oncogenic type II env recombinant. The CWD recombinant accelerated the onset of lymphoma in both strains, but the disease latency in the HRS/J mice was about 2 months longer. Analysis of the recombinant viruses in the HRS/J tumors revealed that the injected type II env recombinant had recombined in vivo with the endogenous ecotropic viruses to generate secondary recombinants with type I envelope genes. In another set of experiments, comparison of complete or partial DNA sequences of the envelope genes from six recombinant proviruses confirmed that the origins of the sequences that encode an amino-terminal region of the TM envelope protein, p15E, distinguish type I envelope genes from type II. Taken together with the results of previous studies, these observations suggest that the differences in the responses of HRS/J and CWD mice to the oncogenic type II env recombinant resulted from an interaction between the viral TM protein and a host factor expressed in HRS/J mice.
Insights
Murine leukemia virus envelope genes differ between mouse strains. HRS/J mice showed longer lymphoma latency due to in vivo recombination with endogenous viruses, suggesting a host factor interaction.
Area of Science:
- Virology
- Immunology
- Genetics
Background:
- Murine leukemia viruses (MLVs) exhibit distinct envelope gene structures in different mouse strains, specifically type I (HRS/J) and type II (CWD) env recombinants.
- Understanding the biological significance of these genotypic differences is crucial for comprehending MLV pathogenesis.
Purpose of the Study:
- To investigate the biological impact of distinct MLV envelope gene structures by examining the differential responses of HRS/J and CWD mice to an oncogenic type II env recombinant.
- To elucidate the mechanisms underlying observed differences in disease latency and viral evolution in response to MLV infection.
Main Methods:
- Inoculation of HRS/J and CWD mice with an oncogenic type II env recombinant MLV.
- Analysis of recombinant viruses within tumors from infected HRS/J mice to identify in vivo recombination events.
- Comparison of complete or partial DNA sequences of envelope genes from six recombinant proviruses.
Main Results:
- The type II env recombinant accelerated lymphoma onset in both HRS/J and CWD mice, but with a ~2-month longer latency in HRS/J mice.
- In HRS/J mice, the inoculated type II env recombinant underwent in vivo recombination with endogenous ecotropic viruses, generating secondary recombinants with type I envelope genes.
- Sequence analysis confirmed that variations in the amino-terminal region of the TM envelope protein (p15E) distinguish type I from type II envelope genes.
Conclusions:
- Differences in MLV envelope gene structures influence disease progression and viral evolution.
- The distinct responses of HRS/J and CWD mice to oncogenic MLV are likely mediated by an interaction between the viral TM protein and a host factor present in HRS/J mice.
- These findings highlight the role of host-virus interactions in determining the outcome of MLV infection and oncogenesis.