Wild type measles virus attenuation independent of type I IFN.
BACKGROUND
Measles virus attenuation has been historically performed by adaptation to cell culture. The current dogma is that attenuated virus strains induce more type I IFN and are more resistant to IFN-induced protection than wild type (wt).


RESULTS
The adaptation of a measles virus isolate (G954-PBL) by 13 passages in Vero cells induced a strong attenuation of this strain in vivo. The adapted virus (G954-V13) differs from its parental strain by only 5 amino acids (4 in P/V/C and 1 in the M gene). While a vaccine strain, Edmonston Zagreb, could replicate equally well in various primate cells, both G954 strains exhibited restriction to the specific cell type used initially for their propagation. Surprisingly, we observed that both G954 strains induced type I IFN, the wt strain inducing even more than the attenuated ones, particularly in human plasmacytoid Dendritic Cells. Type I IFN-induced protection from the infection of both G954 strains depended on the cell type analyzed, being less efficient in the cells used to grow the viral strain.


CONCLUSIONS
Thus, mutations in M and P/V/C proteins can critically affect MV pathogenicity, cellular tropism and lead to virus attenuation without interfering with the alpha/beta IFN system.
Druelle
Johan
J
Inserm, U758, Lyon, F-69365 France. druelle@cervi-lyon.inserm.fr
Sellin
Caroline I
CI
Waku-Kouomou
Diane
D
Horvat
Branka
B
Wild
Fabian T
FT
D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001483:Base Sequence; D002460:Cell Line; D002522:Chlorocebus aethiops; D005814:Genes, Viral; D054884:Host-Pathogen Interactions; D006801:Humans; D007370:Interferon Type I / Q000276:immunology*; D008457:Measles / Q000821:virology; D008459:Measles virus / Q000235:genetics* / Q000472:pathogenicity* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009154:Mutation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D012692:Serial Passage / Q000379:methods; D014709:Vero Cells; D014779:Virus Replication
D000914:Antibodies, Viral; D007370:Interferon Type I