Canine distemper virus infects canine keratinocytes and immune cells by using overlapping and distinct regions located on one side of the attachment protein

Langedijk, J.P.; Janda, Jozef; Origgi, Francesco; Orvell, C.; Vandevelde, Marc; Zurbriggen, Andreas; Plattet, Philippe (2011). Canine distemper virus infects canine keratinocytes and immune cells by using overlapping and distinct regions located on one side of the attachment protein. Journal of virology, 85(21), pp. 11242-54. Baltimore: American Society for Microbiology 10.1128/JVI.05340-11

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The morbilliviruses measles virus (MeV) and canine distemper virus (CDV) both rely on two surface glycoproteins, the attachment (H) and fusion proteins, to promote fusion activity for viral cell entry. Growing evidence suggests that morbilliviruses infect multiple cell types by binding to distinct host cell surface receptors. Currently, the only known in vivo receptor used by morbilliviruses is CD150/SLAM, a molecule expressed in certain immune cells. Here we investigated the usage of multiple receptors by the highly virulent and demyelinating CDV strain A75/17. We based our study on the assumption that CDV-H may interact with receptors similar to those for MeV, and we conducted systematic alanine-scanning mutagenesis on CDV-H throughout one side of the beta-propeller documented in MeV-H to contain multiple receptor-binding sites. Functional and biochemical assays performed with SLAM-expressing cells and primary canine epithelial keratinocytes identified 11 residues mutation of which selectively abrogated fusion in keratinocytes. Among these, four were identical to amino acids identified in MeV-H as residues contacting a putative receptor expressed in polarized epithelial cells. Strikingly, when mapped on a CDV-H structural model, all residues clustered in or around a recessed groove located on one side of CDV-H. In contrast, reported CDV-H mutants with SLAM-dependent fusion deficiencies were characterized by additional impairments to the promotion of fusion in keratinocytes. Furthermore, upon transfer of residues that selectively impaired fusion induction in keratinocytes into the CDV-H of the vaccine strain, fusion remained largely unaltered. Taken together, our results suggest that a restricted region on one side of CDV-H contains distinct and overlapping sites that control functional interaction with multiple receptors.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Research Foci > NeuroCenter
05 Veterinary Medicine > Department of Clinical Veterinary Medicine (DKV) > DKV - Clinical Neurology
05 Veterinary Medicine > Department of Clinical Veterinary Medicine (DKV)
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Experimental Clinical Research
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Animal Pathology
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)
05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH)
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Center for Fish and Wildlife Health (FIWI)

UniBE Contributor:

Janda, Jozef; Origgi, Francesco; Vandevelde, Marc; Zurbriggen, Andreas and Plattet, Philippe

Subjects:

600 Technology > 630 Agriculture

ISSN:

0022-538X

Publisher:

American Society for Microbiology

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:31

Last Modified:

04 Sep 2018 08:46

Publisher DOI:

10.1128/JVI.05340-11

Web of Science ID:

000296254400030

URI:

https://boris.unibe.ch/id/eprint/12062 (FactScience: 218339)

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