Abstract
BackgroundMeasles 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).ResultsThe 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.ConclusionThus, mutations in M and P/V/C proteins can critically affect MV pathogenicity, cellular tropism and lead to virus attenuation without interfering with the α/β IFN system.
Highlights
Measles virus attenuation has been historically performed by adaptation to cell culture
Adaptation of wild type Measles virus (MV) to Vero cells induced 5 mutations in the P/V/C and M genes In a previous study [10], we isolated MV (G954-PBL) from the lymphocytes of a patient and maintained the isolate either in PHA-activated human peripheral blood mononuclear cells (PBMCs) or adapted the virus to Vero cells. During this adaptation to Vero cells, we reported no changes in the amino acid sequences of the two viral glycoproteins, H and F [10]
In order to identify the mutations implicated in the adaptation of the virus (G954-V13) to Vero cells, we sequenced the complete genomes of both viruses
Summary
Measles virus attenuation has been historically performed by adaptation to cell culture. Mass vaccination with live attenuated measles vaccines has greatly reduced the incidence of this disease and its associated pathologies. Most vaccine strains were established after numerous passages on various cell lines. During this period of adaptation, the virus genome mutated in order to replicate efficiently in cell culture and the original viral phenotype has been modified by mechanisms which are still poorly understood. The mutations observed in the RNA genome may be responsible for the replication of the clinical virus in its new host cell at different levels: entry, transcription, translation or budding. Like other viruses of this family, the MV negative RNA genome is protected by the N protein. H (haemagglutinin) and F (fusion) proteins are surface glycoproteins, set in a lipid envelope, lined by the M (matrix) protein, and are (page number not for citation purposes)
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