Canine distemper virus spread and transmission to naive ferrets: Selective pressure on signaling lymphocyte activation moleculedependent entry

Bevan Sawatsky, Roberto Cattaneo, Veronika von Messling

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Upon infection, morbilliviruses such as measles virus, rinderpest virus, and canine distemper virus (CDV) initially target immune cells via the signaling lymphocyte activation molecule (SLAM) before spreading to respiratory epithelia through the adherens junction protein nectin-4. However, the roles of these receptors in transmission from infected to naive hosts have not yet been formally tested. To experimentally addressing this question, we established a model of CDV contact transmission between ferrets. We show here that transmission of wild-type CDV sometimes precedes the onset of clinical disease. In contrast, transmission was not observed in most animals infected with SLAM- or nectin-4-blind CDVs, even though all animals infected with the nectin-4-blind virus developed sustained viremia. There was an unexpected case of transmission of a nectin-4-blind virus, possibly due to biting. Another unprecedented event was transient viremia in an infection with a SLAM-blind virus. We identified three compensatory mutations within or near the SLAM-binding surface of the attachment protein. A recombinant CDV expressing the mutated attachment protein regained the ability to infect ferret lymphocytes in vitro, but its replication was not as efficient as that of wild-type CDV. Ferrets infected with this virus developed transient viremia and fever, but there was no transmission to naive contacts. Our study supports the importance of epithelial cell infection and of sequential CDV H protein interactions first with SLAM and then nectin-4 receptors for transmission to naive hosts. It also highlights the in vivo selection pressure on the H protein interactions with SLAM.

Original languageEnglish (US)
Article numbere00669-18
JournalJournal of virology
Volume92
Issue number15
DOIs
StatePublished - Aug 1 2018

Keywords

  • CDV
  • Canine distemper virus
  • Compensatory mutations
  • Contact transmission
  • Morbilliviruses
  • Nectin-4
  • SLAM
  • Selective pressure
  • Signaling lymphocyte activation molecule

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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