The possible regions to design Human Papilloma Viruses vaccine in Iranian L1 protein

Abstract

Human Papilloma Virus (HPV) genome encodes several proteins, as L1is major capsid protein and L2 is minor capsid protein. Among all HPV types HPV-16 and HPV-18 are the most common high-risk HPV (HR-HPV) types globally and the majority of cases are infected with these types. HPV entry and the initial interaction with the host cell are mainly related to the L1 protein which is the main component of HPV vaccines. The aim of this research was comparison analysis among all Iranian L1 protein sequences submitted in NCBI GenBank to find the major substitutions as well as structural and immune properties of this protein. All sequences HPV L1 protein from Iranian isolates from 2014 to 2016 were selected and obtained from NCBI data bank. "CLC Genomics Workbench" was used to translate alignment. To predict B cell epitopes, we employed several programs. Modification sites such as phosphorylation, glycosylation, and disulfide bonds were determined. Secondary and tertiary structures of all sequences were analyzed. Several mutations were found and major mutations were in amino acid residues 102, 202, 207, 292, 379, and 502. The mentioned mutations showed the minor effect on B cell and physicochemical properties of the L1 protein. Six disulfide bonds were determined in L1 protein and also in several N-link glycosylation and phosphorylation sites. Five L1 loops were determined, which had great potential to be B cell epitopes with high antigenic properties. All in all, this research as the first report from Iran described the tremendous potential of two L1 loops (BC and FG) to induce immune system which can be used as the descent candidate to design a new vaccine against HPV in the Iranian population. In addition, some differences between the reference sequence and Iranian patients' sequences were determined. It is essential to consider these differences to monitor the effectiveness and efficacy of the vaccine for the Iranian population. Our results provide a vast understanding of L1 protein that can be useful for further studies on HPV infections and new vaccine generations.

Mutation Profiles, Glycosylation Site Distribution and Codon Usage Bias of HPV16

“…The L1 protein plays a major role in the receptor binding of HPVs to host cells [5]. L1 protein is the main component of the current HPV prophylactic vaccines, and the variation of its protein sequence is closely related to the effectiveness of the vaccines [46]. Due to the complex design of the multivalent L1-VLP vaccines, the vaccines cannot prevent all types of HPV infection, and some HPVs that can cause mucosal cancer cannot be covered.…”

In silico prediction of T‐cell and B‐cell epitopes of human papillomavirus type 16 L1 protein

“…In this work, the amino acid sequence analysis of L1 protein showed that amino acid substitution was observed in three position: 176 (threonine‐to‐asparagine), 266 (threonine‐to‐alanine), and 353 (threonine‐to‐proline). Although, L1 protein is highly conserved across HPV 16 variants but amino acid substitution in this region seemed to affect recognition by neutralizing antibodies and the expression level of the L1 protein which in turn has an important effect on HPV vaccines development 21 . Studies showed that mutations on the FG Surface Loop of HPV‐16 L1 protein can lead to generate a new serotype and affect recognition by both type‐specific neutralizing antibodies and cross‐reactive antibodies 20,22 .…”

First report of computational protein–ligand docking to evaluate susceptibility to HIV integrase inhibitors in HIV-infected Iranian patients

“…to specific residue in the protein that alters the charge and the structure of the protein. NetPhos [ 11 , 12 ], DISPHOS [ 13 , 14 ], and NetPhosK [ 15 , 16 ] were performed to assess the kinas specific phosphorylation sites in INT proteins, and SCRATCH [ 13 ], DIANNA [ 14 ], VADAR [ 17 ], DbD2 [ 18 ], and PIC server [ 19 ] were used to define the disulfide bonds. Disulfide post-modification analyses showed that mutations might impact the number of bonds and bond patterns.…”