Open AccessLinkage of Reduced Receptor Affinity and Superinfection to Pathogenesis ofTR1.3 Murine Leukemia Virus
Author(s) -
Samuel L. Murphy,
Maeran Chung-Landers,
Marek Honczarenko,
Glen N. Gaulton
Publication year - 2006
Publication title -
journal of virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.617
H-Index - 292
eISSN - 1070-6321
pISSN - 0022-538X
DOI - 10.1128/jvi.80.9.4601-4609.2006
Subject(s) - biology , syncytium , murine leukemia virus , tropism , virology , viral envelope , microbiology and biotechnology , virus , receptor , biochemistry
TR1.3 is a Friend murine leukemia virus (MLV) that induces selectivesyncytium induction (SI) of brain capillary endothelial cells (BCEC),intracerebral hemorrhage, and death. Syncytium induction by TR1.3 hasbeen mapped to a single tryptophan-to-glycine conversion at position102 of the envelope glycoprotein (Env102). The mechanism of SI by TR1.3was 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 andviral particles were not statistically different for TR1.3 and FB29.However, affinity measurements derived using purified envelope receptorbinding domain (RBD) revealed a reduction of >1 log in theKD of TR1.3 RBD relative to FB29 RBD. Whole-virusparticles pseudotyped with TR1.3 Env similarly displayed a markedlyreduced binding avidity compared to FB29-pseudotyped viral particles.Lastly, decreased receptor affinity of TR1.3 Env correlated with thefailure to block superinfection following acute and chronic infectionby TR1.3. These results definitively show that acquisition of a SIphenotype can be directly linked to amino acid changes in retroviralEnv that decrease receptor affinity, thereby emphasizing the importanceof events downstream of receptor binding in the cell fusion process andpathology.