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Nectin-4 interactions govern measles virus virulence in a new model of pathogenesis, the squirrel monkey (Saimiri sciureus)

Delpeut, Sebastien; Sawatsky, Bevan; Wong, Xiao Xiang; Frenzke, Marie; Cattaneo, Roberto; von Messling, Véronika (2017). Nectin-4 interactions govern measles virus virulence in a new model of pathogenesis, the squirrel monkey (Saimiri sciureus) Journal of Virology , vol. 91 , nº 11. e02490. DOI: 10.1128/JVI.02490-16.

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Résumé

In addition to humans, only certain nonhuman primates are naturally susceptible to measles virus (MeV) infection. Disease severity is species dependent, ranging from mild to moderate for macaques to severe and even lethal for certain New World monkey species. To investigate if squirrel monkeys (Saimiri sciureus), which are reported to develop a course of disease similar to humans, may be better suited than macaques for the identification of virulence determinants or the evaluation of therapeutics, we infected them with a green fluorescent protein-expressing MeV. Compared to cynomolgus macaques (Macaca fascicularis) infected with the same virus, the squirrel monkeys developed more-severe immunosuppression, higher viral load, and a broader range of clinical signs typical for measles. In contrast, infection with an MeV unable to interact with the epithelial receptor nectin-4, while causing immunosuppression, resulted in only a mild and transient rash and a short-lived elevation of the body temperature. Similar titers of the wild-type and nectin-4-blind MeV were detected in peripheral blood mononuclear cells and lymph node homogenates, but only the wild-type virus was found in tracheal lavage fluids and urine. Thus, our study demonstrates the importance of MeV interactions with nectin-4 for clinical disease in the new and better-performing S. sciureus model of measles pathogenesis. © 2017 American Society for Microbiology. All Rights Reserved.

Type de document:
Mots-clés libres: Cellular receptors; Immune suppression; Measles virus; Pathogenesis; Primate models
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 24 juin 2017 06:58
Dernière modification: 24 juin 2017 07:00
URI: http://espace.inrs.ca/id/eprint/5345

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