Transgenic mice expressing a soluble form of porcine nectin-1/herpesvirus entry mediator C as a model for pseudorabies-resistant livestock.
An approach to genetically engineered resistance to pseudorabies virus (PRV) infection was examined by using a transgene encoding a soluble form of nectin-1, also known as herpesvirus entry mediator C. Nectin-1 is an alpha-herpesvirus receptor that binds to virion glycoprotein D. Nectin-1 mediates entry of PRV, herpes simplex virus types 1 and 2, and bovine herpesvirus type 1. To assess the antiviral potential of an ectopic expression of the nectin-1 ectodomain in vivo, six transgenic mouse lines expressing a soluble form of nectin-1, consisting of an extracellular domain of porcine nectin-1 and the Fc portion of human IgG1, were generated. All of the transgenic mouse lines showed nearly complete resistance to PRV infection by means of both i.p. and intranasal routes. These results suggest that the introduction into farm animals of a transgene encoding a soluble form of nectin-1 would offer a potent biological approach to generating alpha-herpesvirus-resistant livestock.
Ono
Etsuro
E
Laboratory of Animal Experiment for Disease Model, Research Section of Molecular Pathogenesis, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan. etsuro@igm.hokudai.ac.jp
Amagai
Keiko
K
Taharaguchi
Satoshi
S
Tomioka
Yukiko
Y
Yoshino
Saori
S
Watanabe
Yuki
Y
Cherel
Pierre
P
Houdebine
Louis-Marie
LM
Adam
Micheline
M
Eloit
Marc
M
Inobe
Manabu
M
Uede
Toshimitsu
T
D000818:Animals; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification; D006564:Herpesviridae / Q000472:pathogenicity; D011558:Herpesvirus 1, Suid / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000235:genetics / Q000378:metabolism; D007074:Immunoglobulin G / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D000075983:Nectins; D016133:Polymerase Chain Reaction; D011557:Pseudorabies / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D011991:Receptors, Virus / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012995:Solubility; D034421:Sus scrofa
D015815:Cell Adhesion Molecules; D004279:DNA, Viral; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; C000619010:NECTIN1 protein, human; C000619015:Nectin1 protein, mouse; D000075983:Nectins; D011991:Receptors, Virus; D011994:Recombinant Proteins