Coordinated expression of HPV-6 genes with predominant E4 and E5 expression in laryngeal papilloma

Abstract

Laryngeal papilloma (LP) associated with human papillomavirus (HPV)-6 or-11 infection shows aggressive growth. However, the detailed molecular mechanism of virus-driven tumorigen-esis has not been uncovered fully. HPV-6 viral gene expression and dynamic alterations were in-vestigated with in situ localization of viral DNA and RNA in 13 patients with HPV-6-infected lar-yngeal 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 posi-tive 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 im-munosurveillance avoidance. The newly developed E4-specific monoclonal antibody can be applied to further functional studies and clinical applications such as targeted molecular therapies.