Experimental Adaptation of Wild-Type Canine Distemper Virus (CDV) to the Human Entry Receptor CD150

Please always quote using this URN: urn:nbn:de:bvb:20-opus-96537
  • Canine distemper virus (CDV), a close relative of measles virus (MV), is widespread and well known for its broad host range. When the goal of measles eradication may be achieved, and when measles vaccination will be stopped, CDV might eventually cross the species barrier to humans and emerge as a new human pathogen. In order to get an impression how fast such alterations may occur, we characterized required adaptive mutations to the human entry receptors CD150 (SLAM) and nectin-4 as first step to infect human target cells. Recombinant wild-typeCanine distemper virus (CDV), a close relative of measles virus (MV), is widespread and well known for its broad host range. When the goal of measles eradication may be achieved, and when measles vaccination will be stopped, CDV might eventually cross the species barrier to humans and emerge as a new human pathogen. In order to get an impression how fast such alterations may occur, we characterized required adaptive mutations to the human entry receptors CD150 (SLAM) and nectin-4 as first step to infect human target cells. Recombinant wild-type CDV-A75/17red adapted quickly to growth in human H358 epithelial cells expressing human nectin-4. Sequencing of the viral attachment proteins (hemagglutinin, H, and fusion protein, F) genes revealed that no adaptive alteration was required to utilize human nectin-4. In contrast, the virus replicated only to low titres (102 pfu/ml) in Vero cells expressing human CD150 (Vero-hSLAM). After three passages using these cells virus was adapted to human CD150 and replicated to high titres (105 pfu/ml). Sequence analyses revealed that only one amino acid exchange in the H-protein at position 540 Asp→Gly (D540G) was required for functional adaptation to human CD150. Structural modelling suggests that the adaptive mutation D540G in H reflects the sequence alteration from canine to human CD150 at position 70 and 71 from Pro to Leu (P70L) and Gly to Glu (G71E), and compensates for the gain of a negative charge in the human CD150 molecule. Using this model system our data indicate that only a minimal alteration, in this case one adaptive mutation, is required for adaptation of CDV to the human entry receptors, and help to understand the molecular basis why this adaptive mutation occurs.show moreshow less

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Metadaten
Author: Jürgen Schneider-Schaulies, Maria Bieringer, Jung Woo Han, Sabine Kendl, Mojtaba Khosravi, Philippe Plattet
URN:urn:nbn:de:bvb:20-opus-96537
Document Type:Journal article
Faculties:Medizinische Fakultät / Institut für Virologie und Immunbiologie
Language:English
Parent Title (English):PLoS ONE
Year of Completion:2013
Source:In: PLoS ONE (2013) 8: 3, doi:10.1371/journal.pone.0057488
DOI:https://doi.org/10.1371/journal.pone.0057488
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:antibodies; canine distemper virus; measles virus; microbial mutation; protein sequencing; recombinant proteins; ultraviolet radiation; vero cells
Release Date:2014/04/29
Collections:Open-Access-Publikationsfonds / Förderzeitraum 2013
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung