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      Decoding the Genetic and Structural Features of HPV16 E5 Oncogene in Cervical Cancer Isolates from Pakistan: A Pilot Study

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          Abstract

          Background:

          Many anogenital cancers are caused by high-risk HPV. The most common subtype is HPV16, which is prevalent in the world, including Pakistan. Various amino acid residues in HPV16 E5 are associated with high cell cycle progression and proliferation. Lack of studies on HPV16E5 in Pakistan prompted the current study. This is the first report on the occurrence of pathogenic E5 variant of HPV16 in tissue sections obtained from invasive cervical cancerous patients in Pakistan.

          Methods:

          A subset of 11 samples from HPV-positive biopsies were subjected to E5 gene amplification using PCR and analyzed using bioinformatics programs. The bioinformatics analysis detected mutations causing structural variations, which potentially contribute to the oncogenic properties of proteins.

          Results:

          The two-point mutations, C3979A and G4042A, observed in isolate 11 caused the substitution of isoleucine for leucine and valine at positions 44 and 65 in E5 protein. The rest of the isolates had Leu44Val65 amino acids. Intratypic variations and phylogenetic analysis revealed that the majority of the isolates were closely clustered with European-Asian lineage. Moreover, C3979A and G4042A contributed to higher degree of interactions with host receptors, i.e. EGFR.

          Conclusion:

          This is the first study reporting HPV16 variants in a Pakistani population based on variations in the E5 region. Our findings indicate that isolate 11 has a strong interaction with the intracellular domain of EGFR, which may enhance the generation of downstream signals. Since this was a pilot study to explore E5 gene mutation, future studies with large samples are absolutely needed.

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          Most cited references47

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          The ClusPro web server for protein–protein docking

          ClusPro is a web server that performs rigid-body docking of two proteins by sampling billions of conformations. Low-energy docked structures are clustered, and centers of the largest clusters are used as likely models of the complex.
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            Phylogeny.fr: robust phylogenetic analysis for the non-specialist

            Phylogenetic analyses are central to many research areas in biology and typically involve the identification of homologous sequences, their multiple alignment, the phylogenetic reconstruction and the graphical representation of the inferred tree. The Phylogeny.fr platform transparently chains programs to automatically perform these tasks. It is primarily designed for biologists with no experience in phylogeny, but can also meet the needs of specialists; the first ones will find up-to-date tools chained in a phylogeny pipeline to analyze their data in a simple and robust way, while the specialists will be able to easily build and run sophisticated analyses. Phylogeny.fr offers three main modes. The ‘One Click’ mode targets non-specialists and provides a ready-to-use pipeline chaining programs with recognized accuracy and speed: MUSCLE for multiple alignment, PhyML for tree building, and TreeDyn for tree rendering. All parameters are set up to suit most studies, and users only have to provide their input sequences to obtain a ready-to-print tree. The ‘Advanced’ mode uses the same pipeline but allows the parameters of each program to be customized by users. The ‘A la Carte’ mode offers more flexibility and sophistication, as users can build their own pipeline by selecting and setting up the required steps from a large choice of tools to suit their specific needs. Prior to phylogenetic analysis, users can also collect neighbors of a query sequence by running BLAST on general or specialized databases. A guide tree then helps to select neighbor sequences to be used as input for the phylogeny pipeline. Phylogeny.fr is available at: http://www.phylogeny.fr/
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              The Protein Data Bank

              The Protein Data Bank [PDB; Berman, Westbrook et al. (2000), Nucleic Acids Res. 28 , 235–242; http://www.pdb.org/] is the single worldwide archive of primary structural data of biological macromolecules. Many secondary sources of information are derived from PDB data. It is the starting point for studies in structural bioinformatics. This article describes the goals of the PDB, the systems in place for data deposition and access, how to obtain further information and plans for the future development of the resource. The reader should come away with an understanding of the scope of the PDB and what is provided by the resource.
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                Author and article information

                Journal
                Iran Biomed J
                Iran Biomed J
                IBJ
                Iranian Biomedical Journal
                Pasteur Institute of Iran (Tehran, Iran )
                1028-852X
                2008-823X
                November 2023
                23 August 2023
                : 27
                : 6
                : 388-396
                Affiliations
                [1 ]Atta-Ur-Rehman School of Applied Biosciences, National University of Science and Technology, H-12 Campus, Hucknall Road, Islamabad, Pakistan;
                [2 ]Department of Biotechnology, Virtual University of Pakistan, Rawalpindi, Pakistan;
                [3 ]Department of Molecular Biology and Genetics, Khyber Medical University, Peshawar, Pakistan;
                [4 ]Department of Zoology, The Women University Multan, Multan, Pakistan
                Author notes
                [* ]Corresponding Author: Naureen Ehsan IlahiAtta-Ur-Rehman School of Applied Biosciences, National University of Science and Technology, H-12 Campus, Hucknall Road, Islamabad, Pakistan; Tel.: (+042-111) 880880 (Ext. 8713); E-mail: naureen.ehsan@vu.edu.pk
                Article
                10.61186/ibj.3884
                10826910
                38158635
                513d6147-9905-499b-a5a7-d39a435f12ef

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License, ( http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 10 January 2023
                : 12 August 2023
                Categories
                Full Length

                human papillomavirus 16,oncogenes,uterine cervical neoplasms

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