Infectious virions produced from a human papillomavirus type 18/16 genomic DNA chimera

Craig Meyers, Jennifer L. Bromberg-White, Jiaping Zhang, Michelle E. Kaupas, Janine T. Bryan, Robert S. Lowe, Kathrin U. Jansen

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

The organotypic raft culture system has allowed the study of the differentiation-dependent aspects of the human papillomavirus (HPV) life cycle. However, genetic strategies to more completely understand the HPV life cycle are limited. The generation of chimeric viruses has been a useful tool in other virus systems to analyze infection and replication. To investigate the specificity of the interaction of nonstructural genes of one HPV type with the structural genes of another HPV type, we have replaced the L2 and L1 open reading frames (ORFs) of HPV type 18 (HPV18) with the L2 and L1 ORFs of HPV type 16 (HPV16). The resulting HPV18/16 chimeric construct was introduced into primary keratinocytes, where it was stably maintained episomally at a range of 50 to 100 copies of HPV genomic DNA, similar to that typically found in HPV-infected cells in vivo. The integrity of the HPV18/16 genomic DNA chimera was demonstrated. Upon differentiation in raft cultures, late viral functions, including viral DNA amplification, capsid gene expression, and virion morphogenesis, occurred. Chimeric HPV18/16 virions were purified from the raft cultures and were capable of infecting keratinocytes in vitro. Additionally, infection was specifically neutralized with human HPV16 virus-like particle (VLP)-specific antiserum and not with human HPV18 VLP-specific antiserum. Our data demonstrate that the nonstructural genes of HPV18 functionally interact with the structural genes of HPV16, allowing the complete HPV life cycle to occur. We believe that this is the first report of the propagation of chimeric HPV by normal life cycle pathways.

Original languageEnglish (US)
Pages (from-to)4723-4733
Number of pages11
JournalJournal of virology
Volume76
Issue number10
DOIs
StatePublished - May 7 2002

Fingerprint

Human papillomavirus 18
Human papillomavirus 16
Papillomaviridae
chimerism
virion
Virion
genomics
DNA
Life Cycle Stages
life cycle (organisms)
virus-like particles
Keratinocytes
structural genes
keratinocytes
Open Reading Frames
Genes
Immune Sera
antiserum
open reading frames
Viruses

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Meyers, C., Bromberg-White, J. L., Zhang, J., Kaupas, M. E., Bryan, J. T., Lowe, R. S., & Jansen, K. U. (2002). Infectious virions produced from a human papillomavirus type 18/16 genomic DNA chimera. Journal of virology, 76(10), 4723-4733. https://doi.org/10.1128/JVI.76.10.4723-4733.2002
Meyers, Craig ; Bromberg-White, Jennifer L. ; Zhang, Jiaping ; Kaupas, Michelle E. ; Bryan, Janine T. ; Lowe, Robert S. ; Jansen, Kathrin U. / Infectious virions produced from a human papillomavirus type 18/16 genomic DNA chimera. In: Journal of virology. 2002 ; Vol. 76, No. 10. pp. 4723-4733.
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Meyers, C, Bromberg-White, JL, Zhang, J, Kaupas, ME, Bryan, JT, Lowe, RS & Jansen, KU 2002, 'Infectious virions produced from a human papillomavirus type 18/16 genomic DNA chimera', Journal of virology, vol. 76, no. 10, pp. 4723-4733. https://doi.org/10.1128/JVI.76.10.4723-4733.2002

Infectious virions produced from a human papillomavirus type 18/16 genomic DNA chimera. / Meyers, Craig; Bromberg-White, Jennifer L.; Zhang, Jiaping; Kaupas, Michelle E.; Bryan, Janine T.; Lowe, Robert S.; Jansen, Kathrin U.

In: Journal of virology, Vol. 76, No. 10, 07.05.2002, p. 4723-4733.

Research output: Contribution to journalArticle

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