The human papillomavirus type 16 L1 protein interacts directly with E2 and enhances E2- dependent replication and transcription activation: regulation of HPV16 E2 by the late capsid protein L1

Research output: Contribution to journalArticlepeer-review

Authors

  • Abida Siddiqa
  • Claire James
  • Muhammad Faraz Bhatti

Colleges, School and Institutes

External organisations

  • NUST, Islamabad, Pakistan

Abstract

The human papillomavirus (HPV) E2 protein is a multifunctional protein essential for the control of virus gene expression, genome replication and persistence. E2 is expressed throughout the differentiation-dependent virus life cycle and is functionally regulated by association with multiple viral and cellular proteins. Here, we show for the first time that HPV16 E2 directly associates with the major capsid protein L1, independently of other viral or cellular proteins. We have mapped the L1 binding region within E2 and show that the α-2 helices within the E2 DNA binding domain mediate L1 interaction. Using cell-based assays, we show that co-expression of L1 and E2 results in enhanced transcription and virus origin-dependent DNA replication. Upon co- expression in keratinocytes, L1 reduces nucleolar association of E2 protein and when co-expressed with E1 and E2, L1 is partially recruited to viral replication factories. Furthermore, co-distribution of E2 and L1 was detected in the nuclei of upper suprabasal cells in stratified epithelia of HPV16 genome-containing primary human keratinocytes. Taken together, our findings suggest that the interaction between E2 and L1 is important for the regulation of E2 function during the late events of the HPV life cycle.

Details

Original languageEnglish
Pages (from-to)2274-2285
Number of pages12
JournalJournal of General Virology
Volume96
Early online date24 Apr 2015
Publication statusPublished - 1 Aug 2015