Figure 3.

Cellular shutoff induces a ripple effect on codon usage optimization and the acquisition of internal ribosome entry site (IRES) mutations. In the absence of cellular shutoff with high cellular messenger RNA (mRNA) synthesis (top part of the figure), hepatitis A virus (HAV) shows a very inefficient IRES, a deoptimized codon usage, and very low yields of highly stable capsids. Under conditions of cellular shutoff with a decreased cellular mRNA synthesis (bottom part of the figure), HAV shows an optimized codon usage, a more active IRES, and produces high yields of capsids with subtle folding changes.