Coordinated Expression of HPV-6 Genes with Predominant E4 and E5 Expression in Laryngeal Papilloma.

Taro Ikegami,Hidetoshi Kinjyo,Norimoto Kise,Hiroyuki Maeda,Shinya Agena,Akira Ganaha,Narumi Hasegawa,Masatomo Touyama,Akikazu Murakami,Hitoshi Hirakawa,Mikio Suzuki,Asanori Kiyuna,Takayoshi Kosugi,Narutoshi Tsukahara,Shunsuke Kondo

doi:10.3390/microorganisms9030520

Taro Ikegami, Hidetoshi Kinjyo + Show 13 more

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https://doi.org/10.3390/microorganisms9030520

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Journal: Microorganisms	Publication Date: Mar 3, 2021
Citations: 7	License type: CC BY 4.0

Affiliation: University of the Ryukyus, University of Miyazaki

Abstract

Laryngeal papilloma (LP) associated with human papillomavirus (HPV)-6 or -11 infection shows aggressive growth. However, the detailed molecular mechanism of virus-driven tumorigenesis has not been uncovered fully. HPV-6 viral gene expression and dynamic alterations were investigated with in situ localization of viral DNA and RNA in 13 patients with HPV-6-infected laryngeal papilloma. The average viral load was 4.80 × 105 ± 1.86 × 105 copies/ng DNA. E4, E5a, and E5b mRNAs accounted for 96% of the expression of 9 mRNAs. The alteration of viral DNA load during recurrence paralleled the mRNA expression levels, and the expression of all mRNAs showed a similar curve. E4, E5a, and E5b were expressed in the middle to upper part of the epithelium and were co-expressed in the same cells. E4 immunohistochemistry demonstrated an extensively positive reaction in the upper cell layer in accordance with E4 mRNA expression. These results suggest that individual viral genes are coordinately expressed for viral replication, virus release, and immunosurveillance avoidance. The newly developed E4-specific monoclonal antibody can be applied to further functional studies and clinical applications such as targeted molecular therapies.

Highlights

IntroductionLaryngeal papilloma (LP) is the most common benign epithelial tumor of the larynx, appearing as finger-like projections or multiple fronds of stratified squamous epithelium
Laryngeal papilloma (LP) is the most common benign epithelial tumor of the larynx, appearing as finger-like projections or multiple fronds of stratified squamous epithelium.The typical pathological findings are hyperplasia of basal cells and large vacuolated epithelial cells with clear cytoplasm
11 and 13), phylogenetic analysis revealed that patients 1, 7, and 11 were clustered within the human papillomavirus (HPV)-6a subtype (JN252316) and patients 2 and 3 were categorized as the HPV-6b subgroup (X00203), whereas patients 4–6 and 8–10 were closely related to the HPV-6vc subtype (JN252316)

Summary

Introduction

Laryngeal papilloma (LP) is the most common benign epithelial tumor of the larynx, appearing as finger-like projections or multiple fronds of stratified squamous epithelium. The typical pathological findings are hyperplasia of basal cells and large vacuolated epithelial cells with clear cytoplasm. The estimated incidence of LP is approximately 4 per 100,000 in children and 2 per 100,000 in adults [1]. LP can form multiple tumors and has a high recurrence rate. LP in children sometimes shows aggressive growth with rapid recurrence and tracheobronchial extension [2], the malignant transformation of LP has been reported in less than 3% of cases [3,4]. Frequent surgery and occasional tracheostomies are needed to maintain the airway in some cases [2]. Since human papillomavirus (HPV)-6 and -11 infections are usually detected in LP, these viral infections are thought to be a distinct etiology of LP

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