Pathogenesis of fusion deficient recombinant mouse hepatitis viruses.
In this study we have demonstrated that recombinant viruses carrying the amino acid mutations Q1067H, Q1094H, and L1114R were unable to induce fusion at neutral pH, replicated more efficiently in L2 cells, and that infection was delayed by ammonium chloride. These results suggest that the R120/R121 recombinants most likely use the endosomal pathway to enter cells. In this sense they are similar to the pH-dependent MHV-4 variant OBLV60. We were able to observe an attenuated virulence in vivo, despite the fact that our R120/R121 recombinants replicated to comparable (IC) or higher (IN) titers than the S4R29 recombinant in the brain. Preliminary results showed that the level of inflammation observed in infected mice is consistent with the attenuated virulence, but they cannot be explained by the high titers of replication.
De Groot
L
L
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6076, USA.
Piñón
J D
JD
Phillips
J
J
Lavi
E
E
Weiss
S R
SR
D000818:Animals; D001921:Brain / Q000821:virology; D002460:Cell Line; D018352:Coronavirus Infections / Q000503:physiopathology / Q000821:virology*; D008561:Membrane Fusion; D051379:Mice; D006517:Murine hepatitis virus / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D011995:Recombination, Genetic; D014774:Virulence; D014779:Virus Replication