Recombinant Human Papilloma Virus type 16 L1 protein (VLP)

HPV exists widely in nature and is infected through damage to the skin and mucous membranes. It can be transmitted sexually, vertically between mother and child, or sexually. Different types of HPV infect different epithelial tissues and cause different pathological changes, that is, HPV infection Has obvious tissue specificity. HPV enters the body through damage to epithelial cells and mainly lurks in the basal layer of epidermal cells. Once the time is ripe, it enters keratinocytes and proliferates. It gradually completes its life cycle with the differentiation of epithelial cells. Epithelial cells are usually composed of four layers of cells: basal layer, spinous layer, granular layer and cornified layer. Among them, basal layer cells are the only cells with the ability to divide. Only when the virus infects the basal layer can it survive for a long time and initiate genome replication, causing Persistent changes in cells. The replication process can be divided into three steps: the first step is the adsorption of capsid protein to the cell surface, the second step is DNA replication and gene expression, and the third step is the assembly of virus particles. It is composed of closed circular double-stranded DNA molecules. All ORFs are located on the same DNA strand. Only one strand can be used as a template for transcription. This strand can be divided into three regions: early protein coding region (ER), late protein coding region region (LR) and upstream regulatory region (URR).

Figure 1. Schematic diagram of the late cytosolic trafficking events and nuclear delivery of incoming HPV16 genome.(Source: Keiffer TR, et al., 2021)

E1 protein: A gene with large coding capacity and relatively conserved. The molecular weight of the encoded product is 68KD. It is a nuclear phosphorylated protein. It is an important factor involved in viral DNA replication and may also participate in the process of HPV16-induced cell immortalization. E2 protein: It is a transcriptional activation regulator with DNA-binding properties. It contains two conserved domains. In addition, the E2 protein can reduce the efficiency of cell immortalization caused by HPV16 and can also inhibit the growth of HPV-positive cervical cancer cells. Therefore, the lack of E2 can induce cervical cancer. E4 protein: It can induce the degradation of the epithelial keratinocyte cytoskeleton, and its function may be related to the release of viral particles. E5 protein: encodes a hydrophobic membrane protein, is a platelet growth factor/epidermal growth factor (PDGF/EGF) receptor activator, and has certain transformation potential. E6 protein: encodes a protein with transformation activity, containing 4 Cys-X-X-Cys conserved sequences, which involves the protein's function of binding zinc and cell transformation. The main mechanism may be that the E6 protein combines with the tumor suppressor gene p53 protein to form a complex. It inhibits the negative regulatory effect of p53 on the cell cycle. E7 protein: It is a small nuclear protein containing two Cys-X-X-Cys motifs. It has the characteristics of binding zinc and is related to the transformation activity of E7 protein. The E7 protein blocks the negative regulatory effect of this protein on the cell cycle by forming a complex with the retinoblastoma suppressor gene pRB protein. L1 protein: also known as the main capsid protein, accounting for more than 80% of all structural proteins, with a relative molecular mass of 54x10³ ~58x10³. L1 protein can self-assemble into virus-like particles (VLP) in eukaryotic cells, ranking 202nd Aspartic acid plays a key role in the self-assembly of VLPs. L2 protein: Also known as the minor capsid protein, its relative molecular weight is 63x10³~78x10³. It can also participate in the assembly of VLP and is necessary to stabilize the viral capsid structure.

Taking capsid protein L1 as an example, it first forms a monomer structure through a-helix and β-sheet, then aggregates to form a pentamer, and finally the structure of VLPs is formed through disulfide bonds and hydrogen bonds between multiple pentamers. The antigenic epitope on VLP determines its immunogenicity and antigenicity. Its antigenic epitope includes neutralizing epitope and CTL epitope. Neutralizing epitope includes linear neutralizing epitope and conformational neutralizing epitope. Linear epitope It has a linear structure in the amino acid arrangement, but the conformational epitope is not continuously arranged in the amino acid sequence like the linear epitope. It is composed of amino acid residues distributed discontinuously on the linear amino acid sequence. Only when the protein is formed correctly After the folding structure or VLP assembly is complete, these amino acids are close to each other to form an antigenic epitope. Studies have shown that conformational neutralizing epitopes are more antigenic than linear neutralizing epitopes. The amino acids at positions F50, A266 and 282 on HPV16L1 form a conformational epitope. Replacement of specific amino acids in the conformational epitope by other amino acids will lead to a significant decrease in antigenicity. Linear neutralizing epitopes mainly include aal11~130 and aa174~185 of HPV16L1. Although the antigenicity of linear epitopes is not as strong as conformational epitopes, the vaccine constructed from it is sufficient to protect the human body from HPV infection. The neutralizing epitopes of various types of HPV VLPs have cross-immunoreactivity, and the CTL epitopes of HPV VLPs There are few research reports. aa165~173 located on HPV16L1 are CTL epitopes. Vaccines constructed from CTL epitopes can induce L1-specific CTL responses and lead to tumor regression.

HPV-16 VLP
HPV-16 L1 VLP
HPV-16 Capsid Protein VLP
HPV-16 Virus-like Particle
HPV-16 L1 Capsid VLP
HPV-16 Outer Capsid Protein VLP
HPV-16 Major Capsid Protein VLP
HPV-16 Structural Protein VLP
HPV-16 L1 Assembly VLP