VP0 myristoylation is essential for the late steps of poliovirus assembly and the early steps of infection.
VP0 myristoylation merits exploration as an antiviral target; leaves open therapeutic relevance pending validation beyond this animal model.
We previously described the generation of a set of mutations into a cDNA of poliovirus type 1 in the myristoylation signal of the capsid polypeptide VP4 (D. Marc, G. Drugeon, A.-L. Haenni, M. Girard, and S. van der Werf, EMBO J. 8:2661, 1989). Genomic transcripts synthesized in vitro from the mutated cDNAs were found to be noninfectious upon transfection of permissive cells, and this property correlated with the lack of VP0 myristoylation in vivo. In the study presented here, we analyzed the assembly intermediates that could be recovered from cells transfected with the mutated transcripts. We found that 14S pentamers could still assemble to a certain extent with an unmyristoylated VP0. Furthermore, viral particles sedimenting at 150S and containing capsid polypeptides VP1 to VP4 and virus-specific RNA were detected in the transfected cells. However, these mature virions were less abundant than those recovered after transfection with an infectious transcript, and they were devoid of infectivity. The results suggest that VP0 myristoylation plays a role in the late steps of poliovirus assembly and that the myristate moiety of VP4 may be required in the early steps of poliovirus infection.
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Marc et al. (1990) studied this question.
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