Genomic differences in the background of different severity in juvenile-onset respiratory papillomatoses associated with human papillomavirus type 11

Tamas Gall, Andrea Kis, Timea Zsofia Tata, G. Kardos, L. Gergely, K. Szarka

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

This study aimed to compare complete genome sequences of human papillomavirus (HPV) type 11 from two solitary papillomas (considered minimally aggressive), two moderately (six and nine episodes) and two highly aggressive (30 and 33 episodes) juvenile-onset respiratory papillomatoses. Genomic regions were sequenced using the Sanger method; sequences were compared to available GenBank genomes. Activity of the long control region (LCR) was assessed in HEp-2 cell line using luciferase assays and compared to that of the reference (GenBank Accession Number M14119). Site-directed mutagenesis was performed to confirm the association of polymorphisms with differences in LCR activity. Eleven alterations resulted in amino acid changes in different open reading frames. A72E in E1 and Q86K in E2 proteins were exclusively present in a moderately aggressive disease, L1 alterations A476V and S486F were unique to a severe papillomatosis. HPV11s in both solitary papillomas had identical LCRs containing a T7546C polymorphism, which strongly attenuated LCR activity, as confirmed by sitedirected mutagenesis. This strong attenuator polymorphism was also present in the other four genomes showing significantly higher activities, but in these other alterations with demonstrable but statistically not significant attenuating (A7413C, 7509 T deletion) or enhancing (C7479T, T7904A) effect on transactivating potential (as demonstrated by site-directed mutagenesis) were also detected. LCR activities corresponded well to severity, excepting the highly aggressive papillomatosis with the L1 alterations. Presence of intratypic variants cannot explain differences in severity of respiratory papillomatoses associated with HPV11; virulence seems to be determined by the interaction of multiple genetic differences.

Original languageEnglish
Pages (from-to)353-363
Number of pages11
JournalMedical Microbiology and Immunology
Volume202
Issue number5
DOIs
Publication statusPublished - Oct 2013

Fingerprint

Human papillomavirus 11
Papilloma
Nucleic Acid Databases
Genome
Site-Directed Mutagenesis
Luciferases
Mutagenesis
Open Reading Frames
Virulence
Amino Acids
Cell Line
Proteins

Keywords

  • Clinical course
  • Complete genome comparison
  • HPV11
  • LCR activity

ASJC Scopus subject areas

  • Immunology and Allergy
  • Microbiology (medical)
  • Immunology

Cite this

@article{8cb6e0f2ed844dba86bcd2284105a4d7,
title = "Genomic differences in the background of different severity in juvenile-onset respiratory papillomatoses associated with human papillomavirus type 11",
abstract = "This study aimed to compare complete genome sequences of human papillomavirus (HPV) type 11 from two solitary papillomas (considered minimally aggressive), two moderately (six and nine episodes) and two highly aggressive (30 and 33 episodes) juvenile-onset respiratory papillomatoses. Genomic regions were sequenced using the Sanger method; sequences were compared to available GenBank genomes. Activity of the long control region (LCR) was assessed in HEp-2 cell line using luciferase assays and compared to that of the reference (GenBank Accession Number M14119). Site-directed mutagenesis was performed to confirm the association of polymorphisms with differences in LCR activity. Eleven alterations resulted in amino acid changes in different open reading frames. A72E in E1 and Q86K in E2 proteins were exclusively present in a moderately aggressive disease, L1 alterations A476V and S486F were unique to a severe papillomatosis. HPV11s in both solitary papillomas had identical LCRs containing a T7546C polymorphism, which strongly attenuated LCR activity, as confirmed by sitedirected mutagenesis. This strong attenuator polymorphism was also present in the other four genomes showing significantly higher activities, but in these other alterations with demonstrable but statistically not significant attenuating (A7413C, 7509 T deletion) or enhancing (C7479T, T7904A) effect on transactivating potential (as demonstrated by site-directed mutagenesis) were also detected. LCR activities corresponded well to severity, excepting the highly aggressive papillomatosis with the L1 alterations. Presence of intratypic variants cannot explain differences in severity of respiratory papillomatoses associated with HPV11; virulence seems to be determined by the interaction of multiple genetic differences.",
keywords = "Clinical course, Complete genome comparison, HPV11, LCR activity",
author = "Tamas Gall and Andrea Kis and Tata, {Timea Zsofia} and G. Kardos and L. Gergely and K. Szarka",
year = "2013",
month = "10",
doi = "10.1007/s00430-013-0297-y",
language = "English",
volume = "202",
pages = "353--363",
journal = "Medical Microbiology and Immunology",
issn = "0300-8584",
publisher = "Springer Verlag",
number = "5",

}

TY - JOUR

T1 - Genomic differences in the background of different severity in juvenile-onset respiratory papillomatoses associated with human papillomavirus type 11

AU - Gall, Tamas

AU - Kis, Andrea

AU - Tata, Timea Zsofia

AU - Kardos, G.

AU - Gergely, L.

AU - Szarka, K.

PY - 2013/10

Y1 - 2013/10

N2 - This study aimed to compare complete genome sequences of human papillomavirus (HPV) type 11 from two solitary papillomas (considered minimally aggressive), two moderately (six and nine episodes) and two highly aggressive (30 and 33 episodes) juvenile-onset respiratory papillomatoses. Genomic regions were sequenced using the Sanger method; sequences were compared to available GenBank genomes. Activity of the long control region (LCR) was assessed in HEp-2 cell line using luciferase assays and compared to that of the reference (GenBank Accession Number M14119). Site-directed mutagenesis was performed to confirm the association of polymorphisms with differences in LCR activity. Eleven alterations resulted in amino acid changes in different open reading frames. A72E in E1 and Q86K in E2 proteins were exclusively present in a moderately aggressive disease, L1 alterations A476V and S486F were unique to a severe papillomatosis. HPV11s in both solitary papillomas had identical LCRs containing a T7546C polymorphism, which strongly attenuated LCR activity, as confirmed by sitedirected mutagenesis. This strong attenuator polymorphism was also present in the other four genomes showing significantly higher activities, but in these other alterations with demonstrable but statistically not significant attenuating (A7413C, 7509 T deletion) or enhancing (C7479T, T7904A) effect on transactivating potential (as demonstrated by site-directed mutagenesis) were also detected. LCR activities corresponded well to severity, excepting the highly aggressive papillomatosis with the L1 alterations. Presence of intratypic variants cannot explain differences in severity of respiratory papillomatoses associated with HPV11; virulence seems to be determined by the interaction of multiple genetic differences.

AB - This study aimed to compare complete genome sequences of human papillomavirus (HPV) type 11 from two solitary papillomas (considered minimally aggressive), two moderately (six and nine episodes) and two highly aggressive (30 and 33 episodes) juvenile-onset respiratory papillomatoses. Genomic regions were sequenced using the Sanger method; sequences were compared to available GenBank genomes. Activity of the long control region (LCR) was assessed in HEp-2 cell line using luciferase assays and compared to that of the reference (GenBank Accession Number M14119). Site-directed mutagenesis was performed to confirm the association of polymorphisms with differences in LCR activity. Eleven alterations resulted in amino acid changes in different open reading frames. A72E in E1 and Q86K in E2 proteins were exclusively present in a moderately aggressive disease, L1 alterations A476V and S486F were unique to a severe papillomatosis. HPV11s in both solitary papillomas had identical LCRs containing a T7546C polymorphism, which strongly attenuated LCR activity, as confirmed by sitedirected mutagenesis. This strong attenuator polymorphism was also present in the other four genomes showing significantly higher activities, but in these other alterations with demonstrable but statistically not significant attenuating (A7413C, 7509 T deletion) or enhancing (C7479T, T7904A) effect on transactivating potential (as demonstrated by site-directed mutagenesis) were also detected. LCR activities corresponded well to severity, excepting the highly aggressive papillomatosis with the L1 alterations. Presence of intratypic variants cannot explain differences in severity of respiratory papillomatoses associated with HPV11; virulence seems to be determined by the interaction of multiple genetic differences.

KW - Clinical course

KW - Complete genome comparison

KW - HPV11

KW - LCR activity

UR - http://www.scopus.com/inward/record.url?scp=84885604178&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84885604178&partnerID=8YFLogxK

U2 - 10.1007/s00430-013-0297-y

DO - 10.1007/s00430-013-0297-y

M3 - Article

C2 - 23649705

AN - SCOPUS:84885604178

VL - 202

SP - 353

EP - 363

JO - Medical Microbiology and Immunology

JF - Medical Microbiology and Immunology

SN - 0300-8584

IS - 5

ER -