Delineating morbillivirus entry, dissemination and airborne transmission by studying in vivo competition of multicolor canine distemper viruses in ferrets

PLoS Pathogens

Linda J. Rennick¹  W. Paul Duprex¹  Martin Ludlow¹  Albert D. M. E. Osterhaus²  Thijs Kuiken²  Geert van Amerongen²  Ron A. M. Fouchier²  R. Joyce Verburgh²  Rory D. de Vries²  Alwin de Jong²  Sander Herfst²  Debby van Riel²  Peter R. W. A. van Run²  Rik L. de Swart² 

[1] Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts, United States of America;Department of Viroscience, Postgraduate School of Molecular Medicine, Erasmus MC, Rotterdam, The Netherlands

关键词: Ferrets;    Measles virus;    Flow cytometry;    Confocal laser microscopy;    Canine distemper virus;    Influenza viruses;    Nasal cavity;    Nose;   

DOI  :  10.1371/journal.ppat.1006371

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Identification of cellular receptors and characterization of viral tropism in animal models have vastly improved our understanding of morbillivirus pathogenesis. However, specific aspects of viral entry, dissemination and transmission remain difficult to recapitulate in animal models. Here, we used three virologically identical but phenotypically distinct recombinant (r) canine distemper viruses (CDV) expressing different fluorescent reporter proteins for in vivo competition and airborne transmission studies in ferrets (Mustela putorius furo). Six donor ferrets simultaneously received three rCDVs expressing green, red or blue fluorescent proteins via conjunctival (ocular, Oc), intra-nasal (IN) or intra-tracheal (IT) inoculation. Two days post-inoculation sentinel ferrets were placed in physically separated adjacent cages to assess airborne transmission. All donor ferrets developed lymphopenia, fever and lethargy, showed progressively increasing systemic viral loads and were euthanized 14 to 16 days post-inoculation. Systemic replication of virus inoculated via the Oc, IN and IT routes was detected in 2/6, 5/6 and 6/6 ferrets, respectively. In five donor ferrets the IT delivered virus dominated, although replication of two or three different viruses was detected in 5/6 animals. Single lymphocytes expressing multiple fluorescent proteins were abundant in peripheral blood and lymphoid tissues, demonstrating the occurrence of double and triple virus infections. Transmission occurred efficiently and all recipient ferrets showed evidence of infection between 18 and 22 days post-inoculation of the donor ferrets. In all cases, airborne transmission resulted in replication of a single-colored virus, which was the dominant virus in the donor ferret. This study demonstrates that morbilliviruses can use multiple entry routes in parallel, and co-infection of cells during viral dissemination in the host is common. Airborne transmission was efficient, although transmission of viruses expressing a single color suggested a bottleneck event. The identity of the transmitted virus was not determined by the site of inoculation but by the viral dominance during dissemination.

【 授权许可】

CC BY