Reduced protein expression in a virus attenuated by codon deoptimization

ABSTRACT: A general means of viral attenuation involves the extensive recoding of synonymous codons in the viral genome. The mechanistic underpinnings of this approach remain unclear, however. Using quantitative proteomics and RNA sequencing, we explore the molecular basis of attenuation in a strain of bacteriophage T7 whose major capsid gene was engineered to carry 182 suboptimal codons. We do not detect transcriptional effects from recoding. Proteomic observations reveal that translation is halved for the recoded major capsid gene, and a more modest reduction applies to several co-expressed downstream genes. We observe no changes in protein abundances of other co-expressed genes that are encoded upstream. Viral burst size, like capsid protein abundance, is also decreased by half. Together, these observations suggest that, in this virus, reduced translation of an essential polycistronic transcript and diminished virion assembly form the molecular basis of attenuation.

OTHER RELATED OMICS DATASETS IN: PRJNA379044

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Escherichia Coli (strain K12) Enterobacteria Phage T7

SUBMITTER: Benjamin Jack  

LAB HEAD: Claus O. Wilke

PROVIDER: PXD006502 | Pride | 2018-10-24

REPOSITORIES: Pride