Adaptation of wild-type measles virus to cotton rat lung cells: E89K mutation in matrix protein contributes to its fitness

Abstract

Wild-type measles virus (wtMeV) adapted well to cotton rat lung (CRL) cells after serial passages. In order to evaluate the contributions of the individual genes of wtMeV for adaptation, whole genome sequences of the adapted and original viruses were determined and analyzed. The results showed that there were two mutations in the whole genome of the adapted virus. One mutation was located at the 265th nucleotide in the open reading frame (ORF) of the M gene, resulting in the substitution of the 89th amino acid from E (glutamate) to K (lysine). The other was a silent mutation located at the 4182nd nucleotide in the ORF of the L gene. It was demonstrated that the E89K mutation in the M protein is responsible for the adaptation of wtMeV MV99Y in CRL cells. Cotton rats were infected with adapted virus and the original strain via intranasal inoculation. Virus titer results showed that adapted strain replicated better than the original strain in cotton rat lungs. It is suggested that the E89K mutation also contributes to the enhancement of wtMeV replication in a cotton rat model infected intranasally. The results revealed that the E89K mutation in the M protein plays a key role in wtMeV adaptation in cotton rat and CRL cells.