A helper cell for producing an infectious, replication defective,
coronavirus (or more generally nidovirus) particle cell comprises (a) a
nidovirus permissive cell; (b) a nidovirus replicon RNA comprising the
nidovirus packaging signal and a heterologous RNA sequence, wherein the
replicon RNA further lacks a sequence encoding at least one nidovirus
structural protein; and (c) at least one separate helper RNA encoding the
at least one structural protein absent from the replicon RNA, the helper
RNA(s) lacking the nidovirus packaging signal. The combined expression of
the replicon RNA and the helper RNA in the nidovirus permissive cell
produces an assembled nidovirus particle which comprises the heterologous
RNA sequence, is able to infect a cell, and is unable to complete viral
replication in the absence of the helper RNA due to the absence of the
structural protein coding sequence in the packaged replicon. Compositions
for use in making such helper cells, along with viral particles produced
from such cells, compositions of such viral particles, and methods of
making and using such viral particles, are also disclosed.