This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Google Scholar
Right arrow Articles by Konecsni, T.
Right arrow Articles by Blaas, D.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Konecsni, T.
Right arrow Articles by Blaas, D.

 Previous Article  |  Next Article 

Journal of Virology, November 2009, p. 10922-10930, Vol. 83, No. 21
0022-538X/09/$08.00+0     doi:10.1128/JVI.01312-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Low pH-Triggered Beta-Propeller Switch of the Low-Density Lipoprotein Receptor Assists Rhinovirus Infection {triangledown}

Tuende Konecsni,1 Ursula Berka,2 Angela Pickl-Herk,1 Gerhard Bilek,1 Abdul Ghafoor Khan,1 Leszek Gajdzig,2 Renate Fuchs,2 and Dieter Blaas1*

Max F. Perutz Laboratories, University Departments at the Vienna Biocenter, Department of Medical Biochemistry, Medical University of Vienna, Vienna, Austria,1 Department of Pathophysiology, Medical University of Vienna, Vienna, Austria2

Received 26 June 2009/ Accepted 5 August 2009

Minor group human rhinoviruses (HRVs) bind three members of the low-density lipoprotein receptor (LDLR) family: LDLR proper, very-LDLR (VLDLR) and LDLR-related protein (LRP). Whereas ICAM-1, the receptor of major group HRVs actively contributes to viral uncoating, LDLRs are rather considered passive vehicles for cargo delivery to the low-pH environment of endosomes. Since the Tyr-Trp-Thr-Asp β-propeller domain of LDLR has been shown to be involved in the dissociation of bound LDL via intramolecular competition at low pH, we studied whether it also plays a role in HRV infection. Human cell lines deficient in LDLR family proteins are not available. Therefore, we used CHO-ldla7 cells that lack endogenous LDLR. These were stably transfected to express either wild-type (wt) human LDLR or a mutant with a deletion of the β-propeller. When HRV2 was attached to the propeller-negative LDLR, a lower pH was required for conversion to subviral particles than when attached to wt LDLR. This indicates that high-avidity receptor binding maintains the virus in its native conformation. HRV2 internalization directed the mutant LDLR but not wt LDLR to lysosomes, resulting in reduced plasma membrane expression of propeller-negative LDLR. Infection assays using a CHO-adapted HRV2 variant showed a delay in intracellular viral conversion and de novo viral synthesis in cells expressing the truncated LDLR. Our data indicate that the β-propeller attenuates the virus-stabilizing effect of LDLR binding and thereby facilitates RNA release from endosomes, resulting in the enhancement of infection. This is a nice example of a virus exploiting high-avidity multimodule receptor binding with an intrinsic release mechanism.

* Corresponding author. Mailing address: Max F. Perutz Laboratories, University Departments at the Vienna Biocenter, Department of Medical Biochemistry, Medical University of Vienna, Dr. Bohr Gasse 9/3, A-1030 Vienna, Austria. Phone: 43 1 4277 61630. Fax: 43 1 4277 9616. E-mail: dieter.blaas{at}meduniwien.ac.at

{triangledown} Published ahead of print on 12 August 2009.

Journal of Virology, November 2009, p. 10922-10930, Vol. 83, No. 21
0022-538X/09/$08.00+0     doi:10.1128/JVI.01312-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»