The human papillomavirus type 16 L1 protein directly interacts with E2 and enhances E2-dependent replication and transcription activation.
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 to our knowledge 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.
School of Cancer Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK.|Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), Sector H-12, Kashmir Highway, Islamabad 44000, Pakistan.
Abida
A
Siddiqa
School of Cancer Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK.
Karen Campos
KC
Léon
School of Cancer Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK.
Claire D
CD
James
Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), Sector H-12, Kashmir Highway, Islamabad 44000, Pakistan.
Muhammad Faraz
MF
Bhatti
School of Cancer Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK.
Sally
S
Roberts
School of Cancer Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK.
Joanna L
JL
Parish
D020816:Amino Acid Motifs; D036022:Capsid Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000821:virology; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D052162:Human papillomavirus 16 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000821:virology; D009856:Oncogene Proteins, Viral / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D030361:Papillomavirus Infections / Q000821:virology*; D011485:Protein Binding; D015533:Transcriptional Activation; D014779:Virus Replication
D036022:Capsid Proteins; D004268:DNA-Binding Proteins; C054855:E2 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; C063317:L1 protein, Human papillomavirus type 16