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Journal of Virology, May 2006, p. 4601-4609, Vol. 80, No. 9
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.9.4601-4609.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Linkage of Reduced Receptor Affinity and Superinfection to Pathogenesis of TR1.3 Murine Leukemia Virus

Samuel L. Murphy,1,{dagger} Maeran Chung-Landers,1,{dagger} Marek Honczarenko,2 and Glen N. Gaulton1*

Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104,1 Joint Program in Transfusion Medicine, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts 021152

Received 20 September 2005/ Accepted 18 January 2006

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 KD 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.

* Corresponding author. Mailing address: University of Pennsylvania, 354 BRB II/III, 421 Curie Blvd., Philadelphia, PA 19104-6142. Phone: (215) 898-2874. Fax: (215) 573-7945. E-mail: gaulton{at}mail.med.upenn.edu.

{dagger} These authors contributed equally to this work.

Journal of Virology, May 2006, p. 4601-4609, Vol. 80, No. 9
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.9.4601-4609.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Brindley, M. A., Zhang, B., Montelaro, R. C., Maury, W. (2008). An Equine Infectious Anemia Virus Variant Superinfects Cells through Novel Receptor Interactions. J. Virol. 82: 9425-9432 [Abstract] [Full Text]  
  • Murphy, S. L., Gaulton, G. N. (2007). TR1.3 Viral Pathogenesis and Syncytium Formation Are Linked to Env-Gag Cooperation. J. Virol. 81: 10777-10785 [Abstract] [Full Text]  


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