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Journal of Virology, February 2000, p. 1393-1406, Vol. 74, No. 3
David Axelrod Institute, Wadsworth Center for
Laboratories and Research, New York State Department of Health, Albany,
New York 12201,1 and Institute of
Virology, Department of Infectious Diseases and Immunology, Faculty of
Veterinary Medicine, and Institute of Biomembranes, Utrecht University,
3584 CL Utrecht, The Netherlands2
Received 8 July 1999/Accepted 25 October 1999
Coronaviruses generally have a narrow host range, infecting one or
just a few species. Using targeted RNA recombination, we constructed a
mutant of the coronavirus mouse hepatitis virus (MHV) in which the
ectodomain of the spike glycoprotein (S) was replaced with the highly
divergent ectodomain of the S protein of feline infectious peritonitis
virus. The resulting chimeric virus, designated fMHV, acquired the
ability to infect feline cells and simultaneously lost the ability to
infect murine cells in tissue culture. This reciprocal switch of
species specificity strongly supports the notion that coronavirus host
cell range is determined primarily at the level of interactions between
the S protein and the virus receptor. The isolation of fMHV allowed the
localization of the region responsible for S protein incorporation into
virions to the carboxy-terminal 64 of the 1,324 residues of this
protein. This establishes a basis for further definition of elements
involved in virion assembly. In addition, fMHV is potentially the ideal
recipient virus for carrying out reverse genetics of MHV by targeted
RNA recombination, since it presents the possibility of selecting
recombinants, no matter how defective, that have regained the ability
to replicate in murine cells.
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Retargeting of Coronavirus by Substitution of the
Spike Glycoprotein Ectodomain: Crossing the Host Cell Species
Barrier
*
Corresponding author. Mailing address: David Axelrod
Institute, Wadsworth Center, NYSDOH, New Scotland Ave., P.O. Box 22002, Albany, NY 12201-2002. Phone: (518) 474-1283. Fax: (518) 473-1326. E-mail: masters{at}wadsworth.org.
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