Failure of Gamma Interferon but Not Interleukin-10 Expression in Response to Human Papillomavirus Type 11 E6 Protein in Respiratory Papillomatosis

Abstract

Recurrent respiratory papillomatosis (RRP) is a chronic, debilitating disease of the upper airway caused by human papillomavirus type 6 (HPV-6) or HPV-11. We describe responses of peripheral blood mononuclear cells (PBMC) and T cells from RRP patients and controls to the HPV-11 early proteins E6 and E7. PBMC were exposed in vitro to purified E6 or E7 proteins or transduced with fusion proteins containing the first 11 amino acids of the human immunodeficiency virus type 1 protein tat fused to E6 or E7 (tat-E6/tat-E7). T

Immune Dysregulation and Tumor-Associated Gene Changes in Recurrent Respiratory Papillomatosis: A Paired Microarray Analysis

“…Disease severity criteria (3,8,9) were used to classify the RRP patients into two separate disease categories: severe, or mild/moderate. These disease severity groups were treated as ordinal variables when calculating disease associations.…”

“…We previously reported differences in HPV-specific immune responses by RRP patients and controls that predict disease susceptibility and severity (6)(7)(8)(9). Peripheral blood mononuclear cells (PBMC) from these patients respond to HPV 6/11 E6 protein by expressing T H 2-like cytokines and interleukin (IL)- 10 (8,9).…”

IL-10 expression is regulated by HPV E2 protein in cervical cancer cells

“…induction of il-10 production by the host during chronic infection appears to be one of the viral means of altering the class of the antiviral immune response, and induces generalized immune suppression (38). recent studies by us and others strongly suggest that il-10 is responsible for viral persistence (6,10,27).…”

“…The analysis of regulatory elements in the IL-10 promoter has allowed the identification of transcriptional factor binding sites in this region, which are also recognized by the biological activities of other HPV proteins, such as the e5, e6 and e7 oncoproteins. it has been reported that the transactivation properties of these HPV oncoproteins (33)(34)(35)(36)(37)(38), including HPV11 e6, induces the expression of human il-10 (27). The HPV16 e6 oncoprotein regulates c-fos and fibronectin gene expression through the cAMP response element (cre) (33,34), induces TGF-β1 through the Sp1 regulatory element (17), activates tymidine kinase a mediated by the Gc sequences and caaT box (11), and transactivates the prothymosin α and c-myc promoters (35).…”

Management of Adult Recurrent Respiratory Papillomatosis with Oral Acyclovir Following Micro Laryngeal Surgery: A Case Series

“…The HPV is a commensal organism in humans, with widespread latent infection usually suppressed by the host immune system [12]. Results of recent studies [13,14] suggest that the immune response to HPV proteins is altered in patients with RRP. The use of Photo Dynamic Therapy (PDT) with MesoTetra (Hydroxyphenyl) Chlorin (m-THPC) showed significant efficacy in the treatment of RRP, probably reflecting improvement in the immune response by indirectly immunizing the patient to HPV proteins.…”