Linkage of reduced receptor affinity and superinfection to pathogenesis of TR1.3 murine leukemia virus
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Updated: Aug 9, 2026
Amplification, Next-generation Sequencing, and Genomic DNA Mapping of Retroviral Integration Sites
Published on: March 22, 2016
Samuel L Murphy1, Maeran Chung-Landers, Marek Honczarenko
1Department of Pathology and Laboratory Medicine, University of Pennsylvania, 354 BRB II/III, 421 Curie Blvd., Philadelphia, Pennsylvania 19104-6142, USA.
Abstract:
TR1.3 is a Friend murine leukemia virus (MLV) that induces selective syncytium induction (SI) of brain capillary endothelial cells (BCEC), intracerebral hemorrhage, and death. Syncytium induction by TR1.3 has been mapped to a single tryptophan-to-glycine conversion at position 102 of the envelope glycoprotein (Env102). The mechanism of SI by TR1.3 was examined here in comparison to the non-syncytium-inducing, nonpathogenic MLV FB29, which displays an identical BCEC tropism. Envelope protein expression and stability on both infected cells and viral particles were not statistically different for TR1.3 and FB29. However, affinity measurements derived using purified envelope receptor binding domain (RBD) revealed a reduction of >1 log in the K(D) of TR1.3 RBD relative to FB29 RBD. Whole-virus particles pseudotyped with TR1.3 Env similarly displayed a markedly reduced binding avidity compared to FB29-pseudotyped viral particles. Lastly, decreased receptor affinity of TR1.3 Env correlated with the failure to block superinfection following acute and chronic infection by TR1.3. These results definitively show that acquisition of a SI phenotype can be directly linked to amino acid changes in retroviral Env that decrease receptor affinity, thereby emphasizing the importance of events downstream of receptor binding in the cell fusion process and pathology.
Insights
A specific mutation in the Friend murine leukemia virus (MLV) envelope glycoprotein reduces receptor binding affinity, leading to syncytium induction (SI) and pathology in brain capillary endothelial cells (BCEC). This finding highlights downstream events in cell fusion.
Area of Science:
- Virology
- Molecular Biology
- Pathogenesis
Background:
- Friend murine leukemia virus (MLV) TR1.3 causes syncytium induction (SI) in brain capillary endothelial cells (BCEC), leading to hemorrhage and death.
- This pathogenic phenotype is linked to a specific mutation (Trp102Gly) in the envelope glycoprotein (Env).
Purpose of the Study:
- To elucidate the mechanism of SI induced by MLV TR1.3.
- To compare the Env function of pathogenic TR1.3 with non-pathogenic MLV FB29, which shares BCEC tropism.
Main Methods:
- Compared Env expression, stability, and receptor binding affinity of TR1.3 and FB29.
- Utilized purified envelope receptor binding domain (RBD) and whole-virus particles for binding assays.
- Assessed the impact of Env changes on superinfection blocking.
Main Results:
- No significant differences in Env expression or stability between TR1.3 and FB29.
- TR1.3 Env exhibited >1 log lower binding affinity (K(D)) for its receptor compared to FB29 Env.
- Reduced receptor affinity of TR1.3 Env correlated with impaired superinfection blocking.
Conclusions:
- Acquisition of the SI phenotype is directly linked to amino acid changes in retroviral Env that decrease receptor affinity.
- Events downstream of receptor binding are critical for MLV-induced cell fusion and pathology.
- This study emphasizes the role of receptor affinity modulation in viral pathogenesis.
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