Related Experiment Video
Updated: Jul 7, 2026
Using Reverse Genetics to Manipulate the NSs Gene of the Rift Valley Fever Virus MP-12 Strain to Improve Vaccine Safety and Efficacy
Published on: November 1, 2011
Wild type measles virus attenuation independent of type I IFN
Johan Druelle1, Caroline I Sellin, Diane Waku-Kouomou
1Inserm, U758, Lyon, F-69365 France. druelle@cervi-lyon.inserm.fr
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.
Conclusion:
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.
Insights
Measles virus (MV) adaptation to cell culture can attenuate the virus. Contrary to dogma, attenuated MV strains induced less type I interferon (IFN) and showed altered IFN-induced protection, challenging existing theories.
Area of Science:
- Virology
- Immunology
- Cell Biology
Background:
- Measles virus (MV) attenuation is traditionally achieved through cell culture adaptation.
- The prevailing hypothesis suggests attenuated strains elicit stronger type I interferon (IFN) responses and are more resistant to IFN-induced protection than wild-type (wt) viruses.
Purpose of the Study:
- To investigate the impact of cell culture adaptation on MV pathogenicity and IFN interactions.
- To challenge the current understanding of MV attenuation and its relationship with the type I IFN system.
Main Methods:
- Adaptation of a measles virus isolate (G954-PBL) through 13 passages in Vero cells.
- Analysis of amino acid changes in the adapted strain (G954-V13) compared to the parental strain.
- Assessment of type I IFN induction and IFN-mediated protection in various cell types.
Main Results:
- The adapted G954-V13 strain showed significant in vivo attenuation with only 5 amino acid differences (4 in P/V/C, 1 in M gene).
- Both G954 strains displayed cell-type-specific tropism, unlike the vaccine strain Edmonston Zagreb.
- Wild-type G954 induced higher type I IFN levels than the attenuated strain, particularly in human plasmacytoid Dendritic Cells.
- IFN-induced protection varied by cell type, being less effective in cells used for viral propagation.
Conclusions:
- Mutations in the M and P/V/C proteins significantly influence MV pathogenicity and cellular tropism, leading to attenuation.
- Virus attenuation can occur independently of alterations in the alpha/beta interferon system.
- The study refutes the dogma that attenuated MV strains universally induce more type I IFN and are more resistant to its effects.
Related Concept Videos
01:29Immune Response Against Viral Pathogens
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
01:19Inhibitors of Virion Maturation and Assembly
01:25Inhibitors Of Virion Release