Characterization and experimental transmission of an oncogenic papillomavirus in female macaques

Charles E. Wood, Zigui Chen, J. Mark Cline, Brigitte E. Miller, Robert D. Burk

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Cervical cancer is one of the leading causes of cancer mortality in women worldwide, yet few suitable animal models currently exist for study of this disease. Virtually all cases of cervical cancer in women are caused by specific types of genital human papillomavirus (HPV). In this study, we investigated naturally occurring genital PVs in female cynomolgus macaques (Macaca fascicularis) without breeding contact for at least 3.5 years. Exfoliated cervicovaginal cells from 19 of 54 animals tested positive for at least one PV. Seven different PVs were identified, including four novel genotypes and two genotypes (RhPV-d and RhPV-a) previously identified in rhesus macaques (Macaca mulatta). Four PV types were associated with cervical intraepithelial neoplasia (CIN), which resembled human CIN by endoscopy, cervical cytology, histology, and immunohistochemistry. The presence of CIN was highly associated with PV infection (P < 0.0001). The most prevalent virus type was RhPV-d, which was identified in 60% of animals with CIN. An RhPV-d genome sequenced from a high-grade CIN lesion was found to be phylogenetically related to the highly oncogenic HPV16. Transfer of cervical cytobrush samples from donor animals naturally carrying RhPV-d resulted in new infections in 4 of 12 previously virus-free animals and abnormal cytology and histology in 1 of 4 infected animals after 18 weeks of infection. Experimental transmission was confirmed by E1∧4 reverse transcription-PCR products and RhPV-d sequence identity with the donor variant. These findings identify key similarities between macaque and human oncogenic PVs which should prove useful in the study of viral persistence, carcinogenesis, and therapeutic development.

Original languageEnglish (US)
Pages (from-to)6339-6345
Number of pages7
JournalJournal of Virology
Volume81
Issue number12
DOIs
StatePublished - Jun 2007

Fingerprint

Cervical Intraepithelial Neoplasia
Papillomaviridae
Macaca
neoplasms
Macaca mulatta
uterine cervical neoplasms
Uterine Cervical Neoplasms
Macaca fascicularis
Cell Biology
animals
Histology
cell biology
histology
Infection
Genotype
Tissue Donors
Viruses
infection
viruses
endoscopy

ASJC Scopus subject areas

  • Immunology

Cite this

Characterization and experimental transmission of an oncogenic papillomavirus in female macaques. / Wood, Charles E.; Chen, Zigui; Cline, J. Mark; Miller, Brigitte E.; Burk, Robert D.

In: Journal of Virology, Vol. 81, No. 12, 06.2007, p. 6339-6345.

Research output: Contribution to journalArticle

Wood, Charles E. ; Chen, Zigui ; Cline, J. Mark ; Miller, Brigitte E. ; Burk, Robert D. / Characterization and experimental transmission of an oncogenic papillomavirus in female macaques. In: Journal of Virology. 2007 ; Vol. 81, No. 12. pp. 6339-6345.
@article{8bf7885b646244fbb9f7bb6716b537ea,
title = "Characterization and experimental transmission of an oncogenic papillomavirus in female macaques",
abstract = "Cervical cancer is one of the leading causes of cancer mortality in women worldwide, yet few suitable animal models currently exist for study of this disease. Virtually all cases of cervical cancer in women are caused by specific types of genital human papillomavirus (HPV). In this study, we investigated naturally occurring genital PVs in female cynomolgus macaques (Macaca fascicularis) without breeding contact for at least 3.5 years. Exfoliated cervicovaginal cells from 19 of 54 animals tested positive for at least one PV. Seven different PVs were identified, including four novel genotypes and two genotypes (RhPV-d and RhPV-a) previously identified in rhesus macaques (Macaca mulatta). Four PV types were associated with cervical intraepithelial neoplasia (CIN), which resembled human CIN by endoscopy, cervical cytology, histology, and immunohistochemistry. The presence of CIN was highly associated with PV infection (P < 0.0001). The most prevalent virus type was RhPV-d, which was identified in 60{\%} of animals with CIN. An RhPV-d genome sequenced from a high-grade CIN lesion was found to be phylogenetically related to the highly oncogenic HPV16. Transfer of cervical cytobrush samples from donor animals naturally carrying RhPV-d resulted in new infections in 4 of 12 previously virus-free animals and abnormal cytology and histology in 1 of 4 infected animals after 18 weeks of infection. Experimental transmission was confirmed by E1∧4 reverse transcription-PCR products and RhPV-d sequence identity with the donor variant. These findings identify key similarities between macaque and human oncogenic PVs which should prove useful in the study of viral persistence, carcinogenesis, and therapeutic development.",
author = "Wood, {Charles E.} and Zigui Chen and Cline, {J. Mark} and Miller, {Brigitte E.} and Burk, {Robert D.}",
year = "2007",
month = "6",
doi = "10.1128/JVI.00233-07",
language = "English (US)",
volume = "81",
pages = "6339--6345",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "12",

}

TY - JOUR

T1 - Characterization and experimental transmission of an oncogenic papillomavirus in female macaques

AU - Wood, Charles E.

AU - Chen, Zigui

AU - Cline, J. Mark

AU - Miller, Brigitte E.

AU - Burk, Robert D.

PY - 2007/6

Y1 - 2007/6

N2 - Cervical cancer is one of the leading causes of cancer mortality in women worldwide, yet few suitable animal models currently exist for study of this disease. Virtually all cases of cervical cancer in women are caused by specific types of genital human papillomavirus (HPV). In this study, we investigated naturally occurring genital PVs in female cynomolgus macaques (Macaca fascicularis) without breeding contact for at least 3.5 years. Exfoliated cervicovaginal cells from 19 of 54 animals tested positive for at least one PV. Seven different PVs were identified, including four novel genotypes and two genotypes (RhPV-d and RhPV-a) previously identified in rhesus macaques (Macaca mulatta). Four PV types were associated with cervical intraepithelial neoplasia (CIN), which resembled human CIN by endoscopy, cervical cytology, histology, and immunohistochemistry. The presence of CIN was highly associated with PV infection (P < 0.0001). The most prevalent virus type was RhPV-d, which was identified in 60% of animals with CIN. An RhPV-d genome sequenced from a high-grade CIN lesion was found to be phylogenetically related to the highly oncogenic HPV16. Transfer of cervical cytobrush samples from donor animals naturally carrying RhPV-d resulted in new infections in 4 of 12 previously virus-free animals and abnormal cytology and histology in 1 of 4 infected animals after 18 weeks of infection. Experimental transmission was confirmed by E1∧4 reverse transcription-PCR products and RhPV-d sequence identity with the donor variant. These findings identify key similarities between macaque and human oncogenic PVs which should prove useful in the study of viral persistence, carcinogenesis, and therapeutic development.

AB - Cervical cancer is one of the leading causes of cancer mortality in women worldwide, yet few suitable animal models currently exist for study of this disease. Virtually all cases of cervical cancer in women are caused by specific types of genital human papillomavirus (HPV). In this study, we investigated naturally occurring genital PVs in female cynomolgus macaques (Macaca fascicularis) without breeding contact for at least 3.5 years. Exfoliated cervicovaginal cells from 19 of 54 animals tested positive for at least one PV. Seven different PVs were identified, including four novel genotypes and two genotypes (RhPV-d and RhPV-a) previously identified in rhesus macaques (Macaca mulatta). Four PV types were associated with cervical intraepithelial neoplasia (CIN), which resembled human CIN by endoscopy, cervical cytology, histology, and immunohistochemistry. The presence of CIN was highly associated with PV infection (P < 0.0001). The most prevalent virus type was RhPV-d, which was identified in 60% of animals with CIN. An RhPV-d genome sequenced from a high-grade CIN lesion was found to be phylogenetically related to the highly oncogenic HPV16. Transfer of cervical cytobrush samples from donor animals naturally carrying RhPV-d resulted in new infections in 4 of 12 previously virus-free animals and abnormal cytology and histology in 1 of 4 infected animals after 18 weeks of infection. Experimental transmission was confirmed by E1∧4 reverse transcription-PCR products and RhPV-d sequence identity with the donor variant. These findings identify key similarities between macaque and human oncogenic PVs which should prove useful in the study of viral persistence, carcinogenesis, and therapeutic development.

UR - http://www.scopus.com/inward/record.url?scp=34249932512&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34249932512&partnerID=8YFLogxK

U2 - 10.1128/JVI.00233-07

DO - 10.1128/JVI.00233-07

M3 - Article

VL - 81

SP - 6339

EP - 6345

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 12

ER -