Linkage of reduced receptor affinity and superinfection to pathogenesis of TR1.3 murine leukemia virus.

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.

journal_name

J Virol

journal_title

Journal of virology

authors

Murphy SL,Chung-Landers M,Honczarenko M,Gaulton GN

doi

10.1128/JVI.80.9.4601-4609.2006

subject

Has Abstract

pub_date

2006-05-01 00:00:00

pages

4601-9

issue

9

eissn

0022-538X

issn

1098-5514

pii

80/9/4601

journal_volume

80

pub_type

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