Mutations in HPV18 E1ˆE4 impact virus capsid assembly, infectivity competence, and maturation

The most highly expressed protein during the productive phase of the human papillomavirus (HPV) life cycle is E1ˆE4. Its full role during infection remains to be established. HPV E1ˆE4 is expressed during both the early and late stages of the virus life cycle and contributes to viral genome amplification. In an attempt to further outline the functions of E1ˆE4, and determine whether it plays a role in viral capsid assembly and viral infectivity, we examined wild-type E1ˆE4 as well as four E1ˆE4 truncation mutants. Our study revealed that HPV18 genomes containing the shortest truncated form of E1ˆE4, the 17/18 mutant, produced viral titers that were similar to wild-type virus and significantly higher compared to virions containing the three longer E1ˆE4 mutants. Additionally, the infectivity of virus containing the shortest E1ˆE4 mutation was equivalent to wild-type and significantly higher than the other three mutants. In contrast, infectivity was completely abrogated for virus containing the longer E1ˆE4 mutants, regardless of virion maturity. Taken together, our results indicate for the first time that HPV18 E1ˆE4 impacts capsid assembly and viral infectivity as well as virus maturation.