Iranian Biomedical Journal

en Decoding the Genetic and Structural Features of HPV16 E5 Oncogene in Cervical Cancer Isolates from Pakistan: A Pilot Study Molecular Microbiology Molecular Microbiology مقاله کوتاه Short Communication Background: Many anogenital cancers are caused by high-risk human papillomavirus (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. epidermal growth factor receptor (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. Human papillomavirus 16, Oncogenes, Uterine cervical neoplasms 388 396 http://ibj.pasteur.ac.ir/browse.php?a_code=A-10-5260-1&slc_lang=en&sid=1 Naureen Ehsan Ilahi naureen.ehsan@vu.edu.pk 0000-0003-2372-9403 Yes Atta-Ur-Rehman School of Applied Biosciences, National University of Science and Technology, H-12 Campus, Hucknall Road, Islamabad, Pakistan Nayyer Siddiquec 0000-0003-1178-6347 No Department of Molecular Biology and Genetics, Khyber Medical University, Peshawar, Pakistan Muhammad Ibrahim Rashid 0000-0003-3073-4673 No Department of Biotechnology, Virtual University of Pakistan, Rawalpindi, Pakistan Mamoona Noreen mamoona.noreen@gmail.com 0000-0002-4770-5839 No Department of Zoology, The Women University Multan, Multan, Pakistan Sheeba Murad sheebamall@yahoo.com 0000-0003-0530-5535 No Atta-Ur-Rehman School of Applied Biosciences, National University of Science and Technology, H-12 Campus, Hucknall Road, Islamabad, Pakistan