Mutations in HPV18 E1^E4 Impact Virus Capsid Assembly, Infectivity Competence, and Maturation
by
Jennifer Biryukov 1,†, Jocelyn C. Myers 1,†, Margaret E. McLaughlin-Drubin 1,2, Heather M. Griffin 3, Janice Milici 1, John Doorbar 3 and Craig Meyers 1,*
Jennifer Biryukov 1,†, Jocelyn C. Myers 1,†, Margaret E. McLaughlin-Drubin 1,2, Heather M. Griffin 3, Janice Milici 1, John Doorbar 3 and Craig Meyers 1,*
1
Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
2
Department of Medicine, Brigham and Women’s Hospital, Boston, MA 02215, USA
3
Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Viruses 2017, 9(12), 385; https://doi.org/10.3390/v9120385
Received: 15 November 2017 / Revised: 14 December 2017 / Accepted: 15 December 2017 / Published: 19 December 2017
(This article belongs to the Section Animal Viruses)
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.
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Keywords:
Human Papillomavirus (HPV); HPV18; infection; viral titer; virion maturation; E1^E4
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MDPI and ACS Style
Biryukov, J.; Myers, J.C.; McLaughlin-Drubin, M.E.; Griffin, H.M.; Milici, J.; Doorbar, J.; Meyers, C. Mutations in HPV18 E1^E4 Impact Virus Capsid Assembly, Infectivity Competence, and Maturation. Viruses 2017, 9, 385.
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