The GD1a glycan is a cellular receptor for adenoviruses causing epidemic keratoconjunctivitis

Nilsson, Emma C.; Storm, Rickard J.; Bauer, Johannes; Johansson, Susanne M. C.; Lookene, Aivar; Ångström, Jonas; Hedenström, Mattias; Eriksson, Therese L.; Frängsmyr, Lars; Rinaldi, Simon; Willison, Hugh J.; Domellöf, Fatima Pedrosa; Stehle, Thilo; Arnberg, Niklas
January 2011
Nature Medicine;Jan2011, Vol. 17 Issue 1, p105
Academic Journal
Adenovirus type 37 (Ad37) is a leading cause of epidemic keratoconjunctivitis (EKC), a severe and highly contagious ocular disease. Whereas most other adenoviruses infect cells by engaging CD46 or the coxsackie and adenovirus receptor (CAR), Ad37 binds previously unknown sialic acid-containing cell surface molecules. By glycan array screening, we show here that the receptor-recognizing knob domain of the Ad37 fiber protein specifically binds a branched hexasaccharide that is present in the GD1a ganglioside and that features two terminal sialic acids. Soluble GD1a glycan and GD1a-binding antibodies efficiently prevented Ad37 virions from binding and infecting corneal cells. Unexpectedly, the receptor is constituted by one or more glycoproteins containing the GD1a glycan motif rather than the ganglioside itself, as shown by binding, infection and flow cytometry experiments. Molecular modeling, nuclear magnetic resonance and X-ray crystallography reveal that the two terminal sialic acids dock into two of three previously established sialic acid-binding sites in the trimeric Ad37 knob. Surface plasmon resonance analysis shows that the knob-GD1a glycan interaction has high affinity. Our findings therefore form a basis for the design and development of sialic acid-containing antiviral drugs for topical treatment of EKC.


Related Articles

  • Correction: Both α2,3- and α2,6-Linked Sialic Acids on O-Linked Glycoproteins Act as Functional Receptors for Porcine Sapovirus.  // PLoS Pathogens;Jun2014, Vol. 10 Issue 6, p1 

    A correction to the article "Both α2,3- and α2,6-Linked Sialic Acids on O-Linked Glycoproteins Act as Functional Receptors for Porcine Sapovirus" that was published in a previous issue is presented.

  • Treatment of Viral Keratitis. Pepose, Jay S. // Review of Ophthalmology;Apr2012 Supplement, p11 

    The article focuses on the diagnosis and treatment of herpes simplex virus (HSV) keratitis. It presents statistics on the disease's prevalence and cites considerations for differential diagnosis of HSV. It discusses the antiviral therapy for HSV which includes the use of topical corticosteroids...

  • Prevention of Influenza Pneumonitis by Sialic Acid--Conjugated Dendritic Polymers. Landers, Jeffrey J.; Cao, Zhengyi; Lee, Inhan; Piehler, Lars T.; Myc, Piotr P.; Myc, Andrzej; Hamouda, Tarek; Galecki, Andrzej T.; Baker Jr., James R. // Journal of Infectious Diseases;11/1/2002, Vol. 186 Issue 9, p1222 

    Influenza A viral infection begins by hemagglutinin glycoproteins on the viral envelope binding to cell membrane sialic acid (SA). Free SA monomers cannot block hemagglutinin adhesion in vivo because of toxicity. Polyvalent, generation 4 (G4) SA-conjugated polyamidoamine (PAMAM) dendrimer...

  • Shipyard eye.  // British Medical Journal (Clinical Research Edition);9/5/1981, Vol. 283 Issue 6292, p629 

    Presents several information on shipyard eye infection. Information on epidemic keratoconjunctivitis; Manifestation of the disease; Description of adenovirus type 8.

  • NexBio Cuts Off Influenza Virus from its Entry Route. Breindl, Anette // BioWorld Today;6/4/2008, Vol. 19 Issue 108, p1 

    The article deals with NexBio Inc.'s approach to sialic acids. These acids are part of the glycoproteins on the cell surface that identify which cells a flu virus will bind to and how easily it can be spread from one victim to the next. The company's researchers believe that by targeting the...

  • Aciclovir/cidofovir.  // Reactions Weekly;12/2/2016, Vol. 1630 Issue 1, p14 

    An abstract of the article "A multidrug resistant HSV1 infection occurring under cidofovir treatment for ADV infection in an immunocompromised child: Perspectives to new antiviral drugs" by L. Panetta and others is presented.

  • Epidemiological and virological features of epidemic keratoconjunctivitis due to new human adenovirus type 54 in Japan. Kaneko, Hisatoshi; Suzutani, Tatsuo; Aoki, Koki; Kitaichi, Nobuyoshi; Ishida, Susumu; Ishiko, Hiroaki; Ohashi, Tsutomu; Okamoto, Shigeki; Nakagawa, Hisashi; Hinokuma, Rikutaro; Asato, Yoshimori; Oniki, Shinobu; Hashimoto, Teiko; Iida, Tomohiro; Ohno, Shigeaki // British Journal of Ophthalmology;Jan2011, Vol. 95 Issue 1, p32 

    Background/aims New human adenovirus (HAdV)-54 causes epidemic keratoconjunctivitis (EKC) and is virologically close to and has occasionally been detected as HAdV-8. Taking HAdV-54 into account, we redetermined HAdV type in EKC samples to determine its epidemiology in Japan, and examined the...

  • Analysis of Sialyltransferase-Like Proteins from Oryza sativa. Takashima, Shou; Abe, Tomoko; Yoshida, Shigeo; Kawahigashi, Hiroyuki; Saito, Tamio; Tsuji, Shuichi; Tsujimoto, Masafumi // Journal of Biochemistry;Feb2006, Vol. 139 Issue 2, p279 

    Sialic acids are widely distributed among living creatures, from bacteria to mammals, but it has been commonly accepted that they do not exist in plants. However, with the progress of genome analyses, putative gene homologs of animal sialyltransferases have been detected in the genome of some...

  • Expression of sialidase and dystroglycan in human glomerular diseases. Vogtländer, Nils P. J.; Van der Vlag, Johan; Bakker, Marinka A. H.; Dijkman, Henry B.; Wevers, Ron A.; Campbell, Kevin P.; Wetzels, Jack F. M.; Berden, Jo H. M. // Nephrology Dialysis Transplantation;Feb2010, Vol. 25 Issue 2, p478 

    Background. α-Dystroglycan (α-DG) is a negatively charged glycoprotein that covers the surface of podocytes. A decreased glomerular expression of α-DG has been described in minimal change nephropathy (MCN), but not in focal segmental glomerulosclerosis (FSGS). This was suggested as a...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics