The cell adhesion molecule "CAR" and sialic acid on human erythrocytes influence adenovirus in vivo biodistribution.

PLoS Pathogens
Elena SeiradakeEric J Kremer

Abstract

Although it has been known for 50 years that adenoviruses (Ads) interact with erythrocytes ex vivo, the molecular and structural basis for this interaction, which has been serendipitously exploited for diagnostic tests, is unknown. In this study, we characterized the interaction between erythrocytes and unrelated Ad serotypes, human 5 (HAd5) and 37 (HAd37), and canine 2 (CAV-2). While these serotypes agglutinate human erythrocytes, they use different receptors, have different tropisms and/or infect different species. Using molecular, biochemical, structural and transgenic animal-based analyses, we found that the primary erythrocyte interaction domain for HAd37 is its sialic acid binding site, while CAV-2 binding depends on at least three factors: electrostatic interactions, sialic acid binding and, unexpectedly, binding to the coxsackievirus and adenovirus receptor (CAR) on human erythrocytes. We show that the presence of CAR on erythrocytes leads to prolonged in vivo blood half-life and significantly reduced liver infection when a CAR-tropic Ad is injected intravenously. This study provides i) a molecular and structural rationale for Ad-erythrocyte interactions, ii) a basis to improve vector-mediated gene transfer and iii) a m...Continue Reading

References

Jul 1, 1992·Clinical Microbiology Reviews·J C Hierholzer
Jan 1, 1973·Archiv für die gesamte Virusforschung·L DöhnerH Struy
Feb 1, 1971·Canadian Journal of Microbiology·R G Marusyk, T Yamamoto
Oct 1, 1972·Proceedings of the Society for Experimental Biology and Medicine·T Bächi, C Howe
Jan 1, 1972·Advances in Virus Research·C Howe, L T Lee
Nov 1, 1969·Proceedings of the Society for Experimental Biology and Medicine·G Wadell
Jan 1, 1969·Archiv für die gesamte Virusforschung·E NorrbyH Marusyk
Jan 1, 1967·Archiv für die gesamte Virusforschung·G Wadell, P Skaaret
Dec 1, 1967·Journal of Virology·E NorrbyA Lengyel
Jan 1, 1982·Archives of Virology·H Gelderblom, I Maichle-Lauppe
Feb 1, 1995·Protein Engineering·A C WallaceJ M Thornton
Dec 1, 1996·Journal of Biomolecular NMR·R A LaskowskiJ M Thornton
Dec 1, 1996·Computer Applications in the Biosciences : CABIOS·N GaltierC Gautier
Jan 1, 1997·Archives of Virology·P Pring-AkerblomF E Trijssenaar
Mar 14, 1998·Journal of Virology·P Pring-AkerblomF E Trijssenaar
Mar 25, 1999·Acta Crystallographica. Section D, Biological Crystallography·G N MurshudovE J Dodson
May 13, 1999·Bioinformatics·P GouetF Métoz
Jul 14, 1999·Diagnostic Microbiology and Infectious Disease·C Franzen, A Müller
Dec 10, 1999·Journal of Virology·N ArnbergG Wadell
Aug 21, 2001·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·C SoudaisE J Kremer
Jan 29, 2002·Toxicological Sciences : an Official Journal of the Society of Toxicology·Richard E MorrisseyJames S MacDonald
May 10, 2002·Neuroimaging Clinics of North America·Mark C DeLano, Yue Cao
Apr 30, 2003·The Journal of Biological Chemistry·Jason HowittPaul Freimuth
May 31, 2003·Gene Therapy·G CichonP Pring-Akerblom
Aug 14, 2003·Journal of Virology·J Craig Forrest, Terence S Dermody
Jun 1, 1958·Virology·L ROSEN
Jan 1, 1962·Archiv für die gesamte Virusforschung·H BAUER, R WIGAND
Dec 23, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Claire SoudaisEric J Kremer
Feb 24, 2004·The Journal of Gene Medicine·Eric J Kremer
Jun 25, 2004·Nucleic Acids Research·Ian W DavisDavid C Richardson
Jun 29, 2004·Journal of Virology·Wim P BurmeisterNiklas Arnberg
Aug 6, 2004·Molecular Therapy : the Journal of the American Society of Gene Therapy·Campbell G NicolAndrew H Baker

❮ Previous
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Citations

Mar 4, 2011·Future Microbiology·Daniel HenaffEric J Kremer
Aug 8, 2013·Journal of Cardiovascular Pharmacology·Armen YerevanianRoger J Hajjar
Jun 17, 2014·Human Gene Therapy. Clinical Development
Jul 2, 2014·Molecular Biotechnology·Grit KupganJoshua D Ramsey
Feb 19, 2009·Virology Journal·Nilly ShimonyYosef S Haviv
May 23, 2009·PLoS Pathogens·Sara SalinasEric J Kremer
Aug 7, 2009·Molecular Pharmaceutics·Laura M KasmanChristina Voelkel-Johnson
Oct 1, 2009·Human Gene Therapy·Julien S SenacMichael A Barry
Feb 2, 2010·Applied and Environmental Microbiology·Ingemar von OssowskiAiri Palva
Jul 10, 2010·Virology Journal·Cynthia Lyle, Frank McCormick
Sep 6, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Christopher Y ChenMichael A Barry
Apr 7, 2009·Human Gene Therapy·Leonard W Seymour, Kerry D Fisher
Dec 2, 2009·Human Gene Therapy·Jeroen de VrijGuy Zuber
Aug 30, 2012·Molecular Therapy : the Journal of the American Society of Gene Therapy·Lynda CoughlanAndrew H Baker
Aug 1, 2009·Blood·Eric J Kremer
Apr 24, 2012·Glycobiology·Christoph RademacherJames C Paulson
Oct 20, 2015·Molecular Therapy : the Journal of the American Society of Gene Therapy·Julio Alonso-PadillaAndrew H Baker
Nov 13, 2012·Vascular Pharmacology·Angela C Bradshaw, Andrew H Baker
Jul 17, 2012·Pharmacology & Therapeutics·Keith E RobertsonAndrew H Baker
May 29, 2012·Trends in Molecular Medicine·Johanna K Kaufmann, Dirk M Nettelbeck
May 25, 2012·Trends in Pharmacological Sciences·Niklas Arnberg
Mar 1, 2012·Journal of Controlled Release : Official Journal of the Controlled Release Society·Richard LagaLen W Seymour
Sep 16, 2011·Current Opinion in Structural Biology·Ursula NeuThilo Stehle
Mar 24, 2012·Current Opinion in Virology·Karolina Cupelli, Thilo Stehle
Aug 25, 2015·Current Opinion in Pharmacology·Felix Junyent, Eric J Kremer
Aug 28, 2009·Journal of Cellular Biochemistry·Anne K ZaissHarvey R Herschman
Nov 18, 2014·Nature Chemical Biology·Bärbel S BlaumThilo Stehle
Dec 9, 2014·PloS One·Abhimanyu K SinghMark J van Raaij
Feb 13, 2017·Current Opinion in Structural Biology·Bärbel S Blaum
Jul 4, 2012·Viruses·Carmen San Martín
Jun 10, 2009·Laboratory Investigation; a Journal of Technical Methods and Pathology·Mysore S VeenaRaj K Batra

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Methods Mentioned

BETA
transgenic
flow cytometry
chips
PCR

Software Mentioned

GRASP
CellQuest
REFMAC
SARF
FlowJo
ESPript
PROCHECK
COOT
SEAVIEW
XDS

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