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Journal of Virology, July 2007, p. 7136-7148, Vol. 81, No. 13
0022-538X/07/$08.00+0     doi:10.1128/JVI.00116-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Essential Role of Dengue Virus Envelope Protein N Glycosylation at Asparagine-67 during Viral Propagation{triangledown}

Juan A. Mondotte,1,# Pierre-Yves Lozach,3,# Ali Amara,3,4 and Andrea V. Gamarnik1,2*

Fundación Instituto Leloir, Avenida Patricias Argentinas 435, Buenos Aires 1405, Argentina,1 Consejo Nacional de Investigaciones Científicas y Tecnológicas de Argentina, Buenos Aires C1033AAU, Argentina,2 Laboratoire de Pathogénie Virale Moléculaire, Pasteur Institute, 28 Rue du Dr. Roux, 75724 Paris, France,3 INSERM U819, Pasteur Institute, 28 Rue du Dr. Roux, 75724 Paris, France4

Received 17 January 2007/ Accepted 11 April 2007

Dengue virus envelope protein (E) contains two N-linked glycosylation sites, at Asn-67 and Asn-153. The glycosylation site at position 153 is conserved in most flaviviruses, while the site at position 67 is thought to be unique for dengue viruses. N-linked oligosaccharide side chains on flavivirus E proteins have been associated with viral morphogenesis, infectivity, and tropism. Here, we examined the relevance of each N-linked glycan on dengue virus E protein by removing each site in the context of infectious viral particles. Dengue viruses lacking Asn-67 were able to infect mammalian cells and translate and replicate the viral genome, but production of new infectious particles was abolished. In addition, dengue viruses lacking Asn-153 in the E showed reduced infectivity. In contrast, ablation of one or both glycosylation sites yielded viruses that replicate and propagate in mosquito cells. Furthermore, we found a differential requirement of N-linked glycans for E secretion in mammalian and mosquito cells. While secretion of E lacking Asn-67 was efficient in mosquito cells, secretion of the same protein expressed in mammalian cells was dramatically impaired. Finally, we found that viruses lacking the carbohydrate at position 67 showed reduced infection of immature dendritic cells, suggesting interaction between this glycan and the lectin DC-SIGN. Overall, our data defined different roles for the two glycans present at the E protein during dengue virus infection, highlighting the involvement of distinct host functions from mammalian and mosquito cells during dengue virus propagation.

* Corresponding author. Mailing address: Fundación Instituto Leloir, Avenida Patricias Argentinas 435, Buenos Aires 1405, Argentina. Phone: 54-11-5238-7500. Fax: 54-11-5238-7501. E-mail: agamarnik{at}leloir.org.ar

{triangledown} Published ahead of print on 25 April 2007.

# J.A.M. and P.-Y.L. contributed equally to this work.

Journal of Virology, July 2007, p. 7136-7148, Vol. 81, No. 13
0022-538X/07/$08.00+0     doi:10.1128/JVI.00116-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Kroschewski, H., Sagripanti, J.-L., Davidson, A. D. (2009). Identification of amino acids in the dengue virus type 2 envelope glycoprotein critical to virus infectivity. J. Gen. Virol. 90: 2457-2461 [Abstract] [Full Text]  


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