Tropism illuminated: lymphocyte-based pathways blazed by lethal morbillivirus through the host immune system.
The immunosuppressive properties of morbilliviruses including measles and canine distemper virus (CDV) are well known, but the host cells supporting infection are poorly characterized. To identify these cells, a recombinant CDV expressing green fluorescent protein was produced by reverse genetics based on a wild-type strain lethal for ferrets. This recombinant virus fully retained virulence and blazed three lymphocyte-based pathways through the immune system of its host: first, it infected rapidly and massively circulating B and T cells; second, it took over and damaged secondary lymphatic organs including spleen, lymph nodes, and gut-associated and mucosal lymphoid tissues; third, it infected most thymocytes. In contrast, replication in epithelial cells was initially not detectable, but substantial before host death. Thus, CDV initially infects lymphocytes and massively replicates therein, thereby causing immunosuppression and preparing systemic invasion and host escape.
von Messling
Veronika
V
Molecular Medicine Program and Virology and Gene Therapy Graduate Track, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Milosevic
Dragana
D
Cattaneo
Roberto
R
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D004216:Distemper / Q000276:immunology*; D004217:Distemper Virus, Canine / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D005289:Ferrets; D017930:Genes, Reporter / Q000235:genetics; D005814:Genes, Viral; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007958:Leukocyte Count; D007963:Leukocytes, Mononuclear / Q000821:virology; D008221:Lymphoid Tissue / Q000002:abnormalities / Q000648:ultrastructure; D018185:Morbillivirus Infections / Q000276:immunology; D011991:Receptors, Virus / Q000276:immunology; D011995:Recombination, Genetic; D013601:T-Lymphocytes / Q000276:immunology*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014774:Virulence / Q000235:genetics
D011991:Receptors, Virus; D014764:Viral Proteins; D049452:Green Fluorescent Proteins