Mutations in HPV18 E1^E4 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 E1^E4. Its full role during infection remains to be established. HPV E1^E4 is expressed during both the early and late stages of the virus life cycle and contributes to viral genome amplific...

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Bibliographic Details
Published in:Viruses 2017-12, Vol.9 (12), p.385
Main Authors: Biryukov, Jennifer, Myers, Jocelyn C, McLaughlin-Drubin, Margaret E, Griffin, Heather M, Milici, Janice, Doorbar, John, Meyers, Craig
Format: Article
Language:English
Subjects:
Capsid - metabolism
Cells, Cultured
E1^E4
Fibroblasts - virology
Genomes
HPV18
Human papillomavirus
Human Papillomavirus (HPV)
Human papillomavirus 18 - genetics
Human papillomavirus 18 - physiology
Humans
infection
Infectivity
Life cycles
Maturation
Microbial Viability
Mutation
Oncogene Proteins, Fusion - genetics
Oncogene Proteins, Viral - genetics
Viral Load
viral titer
virion maturation
Virions
Virus Assembly
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Summary:The most highly expressed protein during the productive phase of the human papillomavirus (HPV) life cycle is E1^E4. Its full role during infection remains to be established. HPV E1^E4 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 E1^E4, and determine whether it plays a role in viral capsid assembly and viral infectivity, we examined wild-type E1^E4 as well as four E1^E4 truncation mutants. Our study revealed that HPV18 genomes containing the shortest truncated form of E1^E4, the 17/18 mutant, produced viral titers that were similar to wild-type virus and significantly higher compared to virions containing the three longer E1^E4 mutants. Additionally, the infectivity of virus containing the shortest E1^E4 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 E1^E4 mutants, regardless of virion maturity. Taken together, our results indicate for the first time that HPV18 E1^E4 impacts capsid assembly and viral infectivity as well as virus maturation.
ISSN:1999-4915
1999-4915
DOI:10.3390/v9120385