TY - JOUR
T1 - Amino acid substitutions and an insertion in the spike glycoprotein extend the host range of the murine coronavirus MHV-A59
AU - Thackray, Larissa B.
AU - Holmes, Kathryn V.
N1 - Funding Information:
This work was supported by NIH Grant R01-AI-25231. Sequencing of DNA samples at the University of Colorado Cancer Center DNA Sequencing and Analysis Core Facility was supported by a NIH/NCI Cancer Core Support grant (P30 CA046934).
PY - 2004/7/1
Y1 - 2004/7/1
N2 - The murine coronavirus [murine hepatitis virus (MHV)] is limited to infection of susceptible mice and murine cell lines by the specificity of the spike glycoprotein (S) for its receptor, murine carcinoembryonic antigen cell adhesion molecule 1a (mCEACAM1a). We have recently shown that 21 aa substitutions and a 7-aa insert in the N-terminal region of S are associated with the extended host range of a virus variant derived from murine cells persistently infected with the A59 strain of MHV (MHV-A59). We used targeted RNA recombination (TRR) to generate isogenic viruses that differ from MHV-A59 by the 21 aa substitutions or the 7-aa insert in S. Only viruses with both the 21 aa substitutions and the 7-aa insert in S infected hamster, feline, and monkey cells. These viruses also infected murine cells in the presence of blocking anti-mCEACAM1a antibodies. Thus, relatively few changes in the N-terminal region of S1 are sufficient to permit MHV-A59 to interact with alternative receptors on murine and non-murine cells.
AB - The murine coronavirus [murine hepatitis virus (MHV)] is limited to infection of susceptible mice and murine cell lines by the specificity of the spike glycoprotein (S) for its receptor, murine carcinoembryonic antigen cell adhesion molecule 1a (mCEACAM1a). We have recently shown that 21 aa substitutions and a 7-aa insert in the N-terminal region of S are associated with the extended host range of a virus variant derived from murine cells persistently infected with the A59 strain of MHV (MHV-A59). We used targeted RNA recombination (TRR) to generate isogenic viruses that differ from MHV-A59 by the 21 aa substitutions or the 7-aa insert in S. Only viruses with both the 21 aa substitutions and the 7-aa insert in S infected hamster, feline, and monkey cells. These viruses also infected murine cells in the presence of blocking anti-mCEACAM1a antibodies. Thus, relatively few changes in the N-terminal region of S1 are sufficient to permit MHV-A59 to interact with alternative receptors on murine and non-murine cells.
KW - Extended host range
KW - Murine coronavirus
KW - Persistent infection
KW - Receptor jumping mutants
KW - Spike glycoprotein
KW - Targeted RNA recombination
UR - http://www.scopus.com/inward/record.url?scp=2942744765&partnerID=8YFLogxK
U2 - 10.1016/j.virol.2004.04.005
DO - 10.1016/j.virol.2004.04.005
M3 - Article
C2 - 15207636
AN - SCOPUS:2942744765
SN - 0042-6822
VL - 324
SP - 510
EP - 524
JO - Virology
JF - Virology
IS - 2
ER -