Genetic characterization of variants of HPV‑16, HPV‑18 and HPV‑52 circulating in Italy among general and high‑risk populations

Frati,Elena  Rosanna; Bianchi,Silvia; Amendola,Antonella; Colzani,Daniela; Petrelli,Fabio; Zehender,Gianguglielmo; Tanzi,Elisabetta

doi:10.3892/mmr.2019.10847

Genetic characterization of variants of HPV‑16, HPV‑18 and HPV‑52 circulating in Italy among general and high‑risk populations

Authors:
- Elena Rosanna Frati
- Silvia Bianchi
- Antonella Amendola
- Daniela Colzani
- Fabio Petrelli
- Gianguglielmo Zehender
- Elisabetta Tanzi
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Affiliations: Department of Biomedical Sciences for Health, University of Milan, I‑20133 Milan, Italy, School of Medicinal and Health Products Sciences, University of Camerino, I‑62032 Camerino, Italy, Coordinated Research Centre ‘EpiSoMI’, University of Milan, I‑20133 Milan, Italy
Published online on: November 25, 2019 https://doi.org/10.3892/mmr.2019.10847
Pages: 894-902

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Abstract

Viral factors, such as high‑risk human papillomavirus variants, can increase the risk of viral persistence and influence the progression to cancer. In the present study, the long control region (LCR) of human papillomavirus (HPV)‑16 and HPV‑52, and the L1 region of HPV‑16 and HPV‑18, identified from subjects belonging to both general and high‑risk populations (migrants, HIV+ subjects and adolescent/young people) residing in Italy, were characterized using molecular and phylogenetic techniques. To the best of our knowledge, this is the first Italian study to analyze a large number of sequences (n=458) and report phylogenetic data on the HPV‑52 variants. The phylogenetic analysis showed that 90% of the LCR variants of HPV‑16 and HPV‑52 clustered within lineage A (European lineage) and only sequences identified from subjects belonging to high‑risk populations fell into the non‑European lineages. Analysis of the LCRs revealed a high genomic diversity with a large number of changes. Several mutations in the binding sites for viral and cellular transcription factors characterized the HPV‑16 LCR variants belonging to the African lineages B and C, were observed in subjects with cytological abnormalities (high squamous intraepithelial lesions). The HPV‑16 and HPV‑18 L1 molecular characterization identified 30% of changes in the immune‑dominant epitope loops. These data give a clear picture of the situation in Italy, and a starting point for understanding the molecular pathogenesis and developing molecular diagnostics for HPV, vaccines and other therapeutic approaches in order to control and/or eliminate virus‑induced diseases.

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1	Serrano B, Brotons M, Bosch FX and Bruni L: Epidemiology and burden of HPV-related disease. Best Pract Res Clin Obstet Gynaecol. 47:14–26. 2018. View Article : Google Scholar : PubMed/NCBI
2	De Martel C, Plummer M, Vignat J and Franceschi S: Worldwide burden of cancer attributable to HPV by site, country and HPV type. Int J Cancer. 141:664–670. 2017. View Article : Google Scholar : PubMed/NCBI
3	Westrich JA, Warren CJ and Pyeon D: Evasion of the host immune defences by human papillomavirus. Virus Res. 231:21–33. 2017. View Article : Google Scholar : PubMed/NCBI
4	Burk RD, Harari A and Chen Z: Human papillomavirus genome variants. Virology. 445:232–243. 2013. View Article : Google Scholar : PubMed/NCBI
5	Smith B, Chen Z, Reimers L, van Doorslaer K, Schiffman M, Desalle R, Herrero R, Yu K, Wacholder S, Wang T and Burk RD: Sequence imputation of HPV16 genomes for genetic association studies. PLoS One. 6:e213752011. View Article : Google Scholar : PubMed/NCBI
6	Mammas IN, Spandidos DA and Sourvinos G: Genomic diversity of human papillomaviruses (HPV) and clinical implications: An overview in adulthood and childhood. Infect Genet Evol. 21:220–226. 2014. View Article : Google Scholar : PubMed/NCBI
7	Cornet I, Gheit T, Franceschi S, Vignat J, Burk RD, Sylla BS, Tommasino M and Clifford GM; IARC HPV Variant Study Group, : Human papillomavirus type 16 genetic variants: Phylogeny and classification based on E6 and LCR. J Virol. 86:6855–6861. 2012. View Article : Google Scholar : PubMed/NCBI
8	Chen AA, Gheit T, Franceschi S, Tommasino M and Clifford GM: Human papillomavirus 18 genetic variation and cervical cancer risk worldwide. J Virol. 89:10680–10687. 2015. View Article : Google Scholar : PubMed/NCBI
9	O'Connor M, Chan SY and Bernard HU: Transcription factor binding sites in the long control region of genital HPVs. Human papillomaviruses. A compilation and analysis of nucleic acid and amino acid sequences Los Alamos, New Mexico: Los Alamos National Laboratory; pp. III21–III41. 1995
10	Kirnbauer R, Booy F, Cheng N, Lowy DR and Schiller JT: Papillomavirus L1 major capsid protein self-assembles into virus-like particles that are highly immunogenic. Proc Natl Acad Sci USA. 89:12180–12184. 1992. View Article : Google Scholar : PubMed/NCBI
11	Christensen ND, Dillner J, Eklund C, Carter JJ, Wipf GC, Reed CA, Cladel NM and Galloway DA: Surface conformational and linear epitopes on HPV-16 and HPV-18 L1 virus-like particles as defined by monoclonal antibodies. Virology. 223:174–184. 1996. View Article : Google Scholar : PubMed/NCBI
12	Martins AE, Lucena-Silva N, Garcia RG, Welkovic S, Barboza A, Menezes ML, Maruza M, Tenorio T and Ximenes RA: Prevalence of human papillomavirus infection, distribution of viral types and risk factors in cervical samples from human immunodeficiency virus-positive women attending three human immunodeficiency virus-acquired immune deficiency syndrome reference centres in northeastern Brazil. Mem Inst Oswaldo Cruz. 109:738–747. 2014. View Article : Google Scholar : PubMed/NCBI
13	Bianchi S, Boveri S, Igidbashian S, Amendola A, Urbinati AM, Frati ER, Bottari F, Colzani D, Landoni F, Tanzi E, et al: Chlamydia trachomatis infection and HPV/Chlamydia trachomatis co-infection among HPV-vaccinated young women at the beginning of their sexual activity. Arch Gynecol Obstet. 294:1227–1233. 2016. View Article : Google Scholar : PubMed/NCBI
14	Panatto D, Amicizia D, Bianchi S, Frati ER, Zotti CM, Lai PL, Domnich A, Colzani D, Gasparini R and Tanzi E: Chlamydia trachomatis prevalence and chlamydial/HPV co-infection among HPV-unvaccinated young Italian females with normal cytology. Hum Vaccin Immunother. 11:270–276. 2015. View Article : Google Scholar : PubMed/NCBI
15	Orlando G, Fasolo M, Mazza F, Ricci E, Esposito S, Frati E, Zuccotti GV, Cetin I, Gramegna M, Rizzardini G, et al: Risk of cervical HPV infection and prevalence of vaccine-type and other high-risk HPV types among sexually active teens and young women (13–26 years) enrolled in the VALHIDATE study. Hum Vaccin Immunother. 10:986–994. 2014. View Article : Google Scholar : PubMed/NCBI
16	Orlando G, Tanzi E, Rizzardini G, Chatenoud L, Zanchetta N, Esposito S, Tisi G, Fasolo M, Bosari S, Boero V, et al: Modifiable and Non-modifiable factors related to HPV infection and cervical abnormalities in women at high risk: A cross-sectional analysis from the VALHIDATE Study. Ann Virol Res. 2:10132016.
17	Tanzi E, Amendola A, Bianchi S, Fasolo MM, Beretta R, Pariani E, Zappa A, Frati E and Orlando G: Human papillomavirus genotypes and phylogenetic analysis of HPV-16 variants in HIV-1 infected subjects in Italy. Vaccine. 27 (Suppl 1):A17–A23. 2009. View Article : Google Scholar : PubMed/NCBI
18	Zhang C, Park JS, Grce M, Hibbitts S, Palefsky JM, Konno R, Smith-McCune KK, Giovannelli L, Chu TY, Picconi MA, et al: Geographical distribution and risk association of human papillomavirus genotype 52-variant lineages. J Infect Dis. 210:1600–1604. 2014. View Article : Google Scholar : PubMed/NCBI
19	Frati ER, Bianchi S, Colzani D, Zappa A, Orlando G and Tanzi E: Genetic variability in the major capsid L1 protein of human papillomavirus type 16 (HPV-16) and 18 (HPV-18). Infect Genet Evol. 11:2119–2124. 2011. View Article : Google Scholar : PubMed/NCBI
20	Larkin MA, Blackshields G, Brown NP, Chenna R, McGettigan PA, McWilliam H, Valentin F, Wallace IM, Wilm A, Lopez R, et al: Clustal W and Clustal X version 2.0. Bioinformatics. 23:2947–2948. 2007. View Article : Google Scholar : PubMed/NCBI
21	Tamura K, Stecher G, Peterson D, Filipski A and Kumar S: MEGA6: Molecular evolutionary genetics analysis version 6.0. Mol Biol Evol. 30:2725–2729. 2013. View Article : Google Scholar : PubMed/NCBI
22	Hall TA: BioEdit: A user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucl Acids Symp. 41:95–98. 1999.
23	Saitou N and Nei M: The neighbor-joining method: A new method for reconstructing phylogenetic trees. Mol Biol Evol. 4:406–425. 1987.PubMed/NCBI
24	Kimura M: A simple method for estimating evolutionary rate of base substitutions through comparative studies of nucleotide sequences. J Mol Evol. 16:111–120. 1980. View Article : Google Scholar : PubMed/NCBI
25	Weaver S, Shank SD, Spielman SJ, Li M, Muse SV and Kosakovsky Pond SL: Datamonkey 2.0: A modern web application for characterizing selective and other evolutionary processes. Mol Biol Evol. Jan 2–2018.doi: 10.1093/molbev/msx335 (Epub ahead of print). View Article : Google Scholar
26	Frati ER, Fasoli E, Martinelli M, Colzani D, Bianchi S, Carnelli L, Amendola A, Olivani P and Tanzi E: Sexually transmitted infections: A novel screening strategy for improving women's health in vulnerable populations. Int J Mol Sci. 18:E13112017. View Article : Google Scholar : PubMed/NCBI
27	Marongiu L, Godi A, Parry JV and Beddows S: Human papillomavirus type 16 long control region and E6 variants stratified by cervical disease stage. Infect Genet Evol. 26:8–13. 2014. View Article : Google Scholar : PubMed/NCBI
28	Ning T, Wolfe A, Nie J, Huang W, Chen XS and Wang Y: Naturally occurring single amino acid substitution in the L1 major capsid protein of human papillomavirus type 16: Alteration of susceptibility to antibody-mediated neutralization. J Infect Dis. 216:867–876. 2017. View Article : Google Scholar : PubMed/NCBI
29	Van der Weele P, Meijer CJLM and King AJ: Whole-genome sequencing and variant analysis of human papillomavirus 16 infections. J Virol. 91(pii): e00844–17. 2017.PubMed/NCBI